NAME: ACEPHATE RN: 30560-19-1

Efeitos sobre a sade humana: Evidncias de Carcinogenicidade Classificao C Possvel carcingeno Humano

CLASSIFICATION: C; possible human carcinogen. BASIS FOR CLASSIFICATION: The classification is based on increased incidence of hepatocellular carcinomas and adenomas in female mice. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Limited.[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS). Summary on Acephate (30560-19-1). Available from, as of March 15, 2000: http://www.epa.gov/iris/] **PEER REVIEWED** Cancer Classification: Group C Possible Human Carcinogen[USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for Carcinogenic Potential" (April 2006)] **QC REVIEWED** HUMAN TOXICITY EXCERPTS: /SIGNS AND SYMPTOMS/ Acephate can cause cholinesterase inhibition in humans; that is, it can overstimulate the nervous system causing nausea, dizziness, confusion, and at very high exposures (e.g., accidents or major spills), respiratory paralysis and death.[EPA/Office of Prevention, Pesticides, and Toxic Substances; Fact Sheet for Acephate. 4 p (EPA 738-F-01-013) (September 2001)] **PEER REVIEWED** /SIGNS AND SYMPTOMS/ Organophosphorus cmpd can produce dermal irritation ... /Organophosphorus cmpd/[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1073] **PEER REVIEWED** /SIGNS AND SYMPTOMS/ Toxic effects may include anorexia, abdominal cramps, nausea, vomiting, diarrhea, incontinence, eye changes, weakness, dyspnea, bronchospasm, lacrimation, increased salivation & sweating,

bradycardia, hypotension or hypertension due to asphyxia, cyanosis, & muscular twitching of the eyelids, tongue, face, & neck, possibly progressing to convulsions. Central nervous system symptoms include restlessness, anxiety, dizziness, drowsiness, tremor, ataxia, depression, confusion, & coma. Death may occur from depression of the respiratory or cardiovascular system. Neuropathy appears to be a rare problem with the organophosphorus insecticides now in use. /Organophosphorus insecticides/[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 832] **PEER REVIEWED** SIGNS AND SYMPTOMS/ Organophosphate insecticides ... are potent cholinesterase enzyme inhibitors that act by interfering with the metabolism of acetylcholine, which results in accumulation of acetylcholine at neuroreceptor transmission sites. Exposure produces a broad spectrum of clinical effects indicative of massive overstimulation of the chlorinergic system, including muscarinic effects (parasympathetic), nicotinic effects (sympathetic and motor), and CNS effects. These effects present clinically as feeling of headache, weakness, dizziness, blurred vision, psychosis, respiratory difficulty, paralysis, convulsions, and coma. Typical findings are given by the mnemonic "SLUD." which stands for salivation, lacrimation, urination, and defecation. A small percentage of patients may fail to demonstrate miosis, a classic diagnostic hallmark. Onset of clinical manifestation of organophosphate poisoning usually occurs within 12 hours of exposure.

SIGNS AND SYMPTOMS/ The signs of poisoning due to organophosphorus cmpd are those due to accumulation of acetylcholine & hence overstimulation of parasympathetic nervous system. It is usual to divide them under 3 headings: muscarinic, nicotinic & central. Muscarinic signs ... consist of hypersalivation, lacrimation, sweating & nasal discharge. Miosis, dyspnea, vomiting, diarrhea & frequency of urination ... Nicotinic effects consist of fasciculation of muscles, weakness & paralysis. Central nervous system effects include nervousness, apprehension, ataxia, convulsions & coma. Death is due to resp failure, or sometimes cardiac arrest. There is little difference between signs produced by different organophosphorus compounds, but route of absorption may influence one system more than another.

CASE REPORTS/ Two autopsy cases, where the individuals were suspected of

having ingested acephate, an organophosphorous insecticide, are reported. Acephate and its active metabolite, methamidophos (MP), were analyzed in the biological fluids by GC/MS, using the salting out method with liquid-liquid extraction columns. The first case was that of a 70-year-old man whose blood acephate was 149 ug/mL, and MP was 3.0 ug/mL. Serum pseudocholinesterase (ChE) activity was inhibited. No remarkable finding of injury or disease was determined as the cause of his death, but acute poisoning by acephate was mostly suspected. The second case was that of a 60-year-old man. A deep gash in the left neck injured the left common carotid artery in addition to the severely ischemic state of the primary organs.[Tanaka T et al; J Forensic Sci 50 (4): 933-6 (2005)] **PEER

skin

/SURVEILLANCE/ An investigation was conducted of inhalation and

acephate exposures in pesticide formulation workers. The cohort consisted of four persons employed at a small Italian pesticide formulation factory. Breathing zone samples were collected over a full 8 hr shift and analyzed for acephate. Gauze pads were attached to the hands, face, and body of two workers to measure skin exposure. Urine samples were collected daily and analyzed for acephate and methamidophos, a major acephate metabolite. Venous blood samples were collected and analyzed for erythrocyte acetylcholinesterase and plasma cholinesterase. Median 8 hour time weighted acephate concentrations ranged from 0.278 to 2.170 mg/cu m. Urine acephate concentrations ranged from 1 to 10 mg/L, median 0.4 to 1.1 mg/L. Methamidophos was not detected in any samples. Median total skin deposition of acephate ranged from 26.1 to 41.9 mg/day. Assuming that 30 to 50% of the breathing zone exposure and 10 to 20% of the skin dose were absorbed, the median intake of acephate was estimated to be 10 to 20 mg/day. Skin absorption was significantly correlated with urinary excretion of acephate. No significant changes in acetylcholinesterase or plasma cholinesterase activity were noted in subjects whose urinary

acephate concentrations averaged 1 to 2 mg/L or less. Higher urinary acephate concentrations were associated with a 20% decrease in plasma cholinesterase and an 18% decrease in acetylcholinesterase activity. These decreases were not considered biologically significant.[Maroni M et al; Arch Environ Contam Toxicol 19 (5): 782-8 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2241237" target=new>PubMed Abstract /OTHER TOXICITY INFORMATION/ The Lineweaver-Burk plot of the activity of human serum cholinesterase against the concentration of butyrylthiocholineiodide was shown by two intersecting lines. The Hill plot of cholinesterase activity was linear over the entire range of the substrate concentration. The n value, an interaction coefficient, was less than 1.0 (about 0.8). ... Acephate, one of the organophosphorous insecticides, inhibited the activity of cholinesterase. Acephate at concentration under 1.25 mM (about 230 ppm in serum) did not inhibit the activity of cholinesterase. The minimum concentration of acephate inhibition of cholinesterase activity was at 2.5 mM. An equilibrium constant (K) can be used as an indicator of inhibitory effect on cholinesterase. The serum cholinesterase activity of workers who were exposed to acephate is not affected when the concentration of acephate in serum is less than 200 ppm. ... The inhibitory effect of acephate on cholinesterase decreased after the incubation with S9 mixture. [Ando M, Wakamatsu K; J Toxicol Sci 7 (3): 185-92 (1982)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7154130" target=new>PubMed Abstract SKIN, EYE AND RESPIRATORY IRRITATIONS: Organophosphorus cmpd can produce dermal irritation but most are weak sensitizers. /Organophosphorus cmpd/[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1073] **PEER REVIEWED** MEDICAL SURVEILLANCE:

Workers handling &amp; applying pesticides must undergo an annual medical examination at the beginning of each agricultural season. Contraindications for work with /organophosphorus pesticides/ are organic diseases of the central nervous system, mental disorders &amp; epilepsy, pronounced endocrine &amp; vegetative disorders, pulmonary tuberculosis, bronchial asthma, chronic respiratory diseases, cardiovascular diseases &amp; circulatory disorders, gastrointestinal diseases (peptic ulcer), gastroenterocolitis, diseases of liver &amp; kidneys, eye diseases (chronic conjunctivitis &amp; keratitis). The blood cholinesterase activity must be determined before work starts. In the event of prolonged work periods, this activity should be determined at intervals of 3-4 days. Persons exhibiting a fall in cholinesterase activity of 25% or more must be transferred to other work where they are not exposed to organophosphorus pesticides until this activity is completely restored. Persons with initial signs of indisposition should cease work with pesticides. /Organophosphorus pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1646] **PEER REVIEWED** POPULATIONS AT SPECIAL RISK: In the United States, organophosphates cause perhaps up to 200 deaths per year; in California, four out of five systemic poisonings from agricultural chemicals result from exposure to organophosphate compounds. /Organophosphate pesticides/[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1071] **PEER REVIEWED** PROBABLE ROUTES OF HUMAN EXPOSURE: NIOSH (NOES Survey 1981-1983) has statistically estimated that 770 (378 of these are female) workers are potentially exposed to acephate in the USA(1). The NOES Survey does not include farm workers; therefore, the actual number of exposures may be underestimated. Occupational exposure to acephate may occur through inhalation of dust and dermal contact with this

Four

compound at workplaces where acephate is produced or used(SRC).

workers involved in the formulation of acephate products were monitored over an 8 day period to determine inhalation and dermal exposures(2); median air concns (8 hr TWA) ranged from 0.278 to 2.17 mg/cu m and median total-body skin deposition ranged from 26.1 to 41.9 mg/day(2). Monitoring data indicate that the general population may be exposed to acephate via ingestion of food(SRC).[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983). Available at http://www.cdc.gov/noes/noes1/t0473sic.html as of Jan 12, 2007. (2) Maroni M et al; Arch Environ Contam Toxicol 19: 782-8 (1990)] **PEER REVIEWED** AVERAGE DAILY INTAKE: FOOD: The FDA's Total Diet Study for 1988 reported the following average daily intakes (in ug/kg body wt/day) for acephate(1): infants (611 mo old) - 0.0105, 14-16 yr old males-0.0080, 60-65 yr old females0.0104(1). The FDA's Total Diet Study for 1982-1984 reported the following average daily intakes (in ug/kg body wt/day) for acephate(1): infants (611 mo old) - 0.0003, toddlers (2 yr old): 0.0011, 14-16 yr old females: 0.0008, 14-16 yr old males-0.0016, 25-30 yr-old females-0.0025, 25-30 yr old males-0.0026, 60-65 yr old females-0.0022, 60-65 yr old males-0.0017(2).[(1) FDA; Food &amp; Drug Administration Pesticide Program: Residues in Foods-1988, Washington DC: FDA (1989) (2) Gunderson EL; J Assoc Off Anal Chem 71: 1200-9 (1988)] **PEER REVIEWED** EMERGENCY MEDICAL TREATMENT: EMERGENCY MEDICAL TREATMENT: EMT COPYRIGHT DISCLAIMER: Portions of the POISINDEX(R) and MEDITEXT(R) database have been provided here for general reference. THE COMPLETE POISINDEX(R) DATABASE OR MEDITEXT(R) DATABASE SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. The use of the POISINDEX(R) and MEDITEXT(R) databases is at your sole risk. The POISINDEX(R) and MEDITEXT(R) databases are provided "AS IS" and

"as available" for use, without warranties of any kind, either expressed or implied. Micromedex makes no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the POISINDEX(R) and MEDITEXT(R) databases. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Micromedex does not assume any responsibility or risk for your use of the POISINDEX(R) or MEDITEXT(R) databases. Copyright 1974-2011 Thomson MICROMEDEX. All Rights Reserved. Any duplication, replication, "downloading," sale, redistribution or other use for commercial purposes is a violation of Micromedex' rights and is strictly prohibited.<p>The following Overview, *** ACEPHATE ***, is relevant for this HSDB record chemical. LIFE SUPPORT: o This overview assumes that basic life support measures have been instituted. CLINICAL EFFECTS: 0.2.1 SUMMARY OF EXPOSURE 0.2.1.1 ACUTE EXPOSURE A) Acephate is an organophosphate compound. The following are signs and symptoms from organophosphates in general, which are due to the anticholinesterase activity of this class of compounds. All of these effects may not be documented for acephate, but could potentially occur in individual cases. B) USES: Acephate is used as an insecticide and registered for use by the US Environmental Protection Agency for a variety of fruit and vegetable crops, in food handling establishments, ornamental plants, and for use in and around the home. It is both a contact and systemic insecticide. C) TOXICOLOGY: Organophosphates competitively inhibit pseudocholinesterase and acetylcholinesterase, preventing hydrolysis and inactivation of acetylcholine. Acetylcholine accumulates at nerve junctions, causing malfunction of the sympathetic, parasympathetic, and peripheral nervous systems and some of the CNS. Clinical signs of cholinergic excess can develop. D) EPIDEMIOLOGY: Exposure to organophosphates is common, but serious toxicity is unusual in the US. Common source of severe poisoning in developing countries. E) WITH POISONING/EXPOSURE 1) MILD TO MODERATE POISONING: MUSCARINIC EFFECTS: Can include bradycardia, salivation, lacrimation, diaphoresis, vomiting, diarrhea, urination, and miosis. NICOTINIC EFFECTS: Tachycardia, hypertension, mydriasis, and muscle cramps. Based on animal studies in rats, acephate is a relatively weak cholinesterase inhibitor when given orally; it was approximately six

orders of magnitude weaker. SEVERE POISONING: MUSCARINIC EFFECTS: Bronchorrhea, bronchospasm, and acute lung injury. NICOTINIC EFFECTS: Muscle fasciculations, weakness, and respiratory failure. CENTRAL EFFECTS: CNS depression, agitation, confusion, delirium, coma, and seizures. Hypotension, ventricular dysrhythmias, metabolic acidosis, pancreatitis, and hyperglycemia can also develop. 3) DELAYED EFFECTS: Intermediate syndrome is characterized by paralysis of respiratory, cranial motor, neck flexor, and proximal limb muscles 1 to 4 days after apparent recovery from cholinergic toxicity, and prior to development of delayed peripheral neuropathy. Manifestations can include the inability to lift the neck or sit up, ophthalmoparesis, slow eye movements, facial weakness, difficulty swallowing, limb weakness (primarily proximal), areflexia, and respiratory paralysis. Recovery begins 5 to 15 days after onset. Distal sensory-motor polyneuropathy may rarely develop 6 to 21 days following exposure to some organophosphate compounds, however, it has not yet been reported in humans after exposure to acephate. Characterized by burning or tingling followed by weakness beginning in the legs which then spreads proximally. In severe cases, it may result in spasticity or flaccidity. Recovery requires months and may not be complete. 4) CHILDREN: May have different predominant signs and symptoms than adults (more likely CNS depression, stupor, coma, flaccidity, dyspnea, and seizures). Children may also have fewer muscarinic and nicotinic signs of intoxication (ie, secretions, bradycardia, fasciculations and miosis) as compared to adults. 5) INHALATION EXPOSURE: Organophosphate vapors rapidly produce mucous membrane and upper airway irritation and bronchospasm, followed by systemic muscarinic, nicotinic and central effects if exposed to significant concentrations. 0.2.3 VITAL SIGNS 0.2.4 HEENT 0.2.4.1 ACUTE EXPOSURE A) Miosis, lacrimation, and blurred vision are common; mydriasis may occur in severe poisonings. Opsoclonus has occurred rarely. B) Excessive salivation commonly occurs. 0.2.5 CARDIOVASCULAR 0.2.5.1 ACUTE EXPOSURE A) Bradycardia, hypotension and chest pain may occur. Tachycardia is also common. Dysrhythmias and conduction defects may occur in severe poisonings. 0.2.6 RESPIRATORY 0.2.6.1 ACUTE EXPOSURE A) Acute respiratory insufficiency is the main cause of death in acute poisonings. B) Dyspnea, rales, bronchorrhea or tachypnea may be noted. Pulmonary edema may develop in severe cases. 2)

Bronchospasm may occur in previously sensitized asthmatics or as a pharmacological muscarinic effect. 0.2.7 NEUROLOGIC 0.2.7.1 ACUTE EXPOSURE A) Headache, dizziness, muscle spasms and profound weakness are common. Alterations of level of consciousness, seizures and coma may occur. Seizures may be more common in children. B) Peripheral neuropathy of the mixed sensory-motor type may be delayed in onset by 6 to 21 days. Recovery may be slow or incomplete. 0.2.8 GASTROINTESTINAL 0.2.8.1 ACUTE EXPOSURE A) Vomiting, diarrhea, fecal incontinence and abdominal pain may occur. B) Pancreatitis has been reported with organophosphate poisoning. 0.2.10 GENITOURINARY 0.2.10.1 ACUTE EXPOSURE A) Increased urinary frequency or, in severe cases, urinary incontinence has occurred. B) Immune-complex nephropathy with proteinuria and/or amorphous crystalluria has been reported following acute organophosphate exposure. 0.2.11 ACID-BASE 0.2.11.1 ACUTE EXPOSURE A) Metabolic acidosis has occurred in several severe poisonings. 0.2.13 HEMATOLOGIC 0.2.13.1 ACUTE EXPOSURE A) The hallmark of organophosphate poisoning is inhibition of plasma pseudocholinesterase and erythrocyte acetylcholinesterase. Acephate is a relatively weak cholinesterase inhibitor. B) Alteration in prothrombin time and/or tendency to bleeding may occur. 0.2.14 DERMATOLOGIC 0.2.14.1 ACUTE EXPOSURE A) Sweating is a consistent but not universal sign. B) Acephate was not a sensitizer in guinea pigs. 0.2.15 MUSCULOSKELETAL 0.2.15.1 ACUTE EXPOSURE A) Muscle weakness, fatigability and fasciculations are common findings and may be delayed in onset by several days. Paralysis may supervene. 0.2.16 ENDOCRINE 0.2.16.1 ACUTE EXPOSURE A) Hyperglycemia can occur in severe organophosphate poisoning. 0.2.17 METABOLISM 0.2.17.1 ACUTE EXPOSURE A) Acephate can inhibit reduced cytochrome c oxidase in alkaline conditions, by a mechanism possibly similar to that of carbon monoxide. 0.2.18 PSYCHIATRIC 0.2.18.1 ACUTE EXPOSURE A) Decreased vigilance, hallucinations, defects in

C)

expressive language and cognitive function, impaired memory, depression, anxiety or irritability and psychosis have been reported, more commonly in people with other clinical signs of organophosphate poisoning. 0.2.20 REPRODUCTIVE HAZARDS A) At the time of this review, there was no data available to assess the potential human effects of exposure to this agent during pregnancy or lactation. B) Sporadic reports of human birth defects related to organophosphates have not been fully verified. C) ANIMAL STUDIES - Acephate was not teratogenic in rats and mice studies It did affect sperm motility and fertility in male rats. 0.2.21 CARCINOGENICITY 0.2.21.1 IARC CATEGORY A) IARC Carcinogenicity Ratings for CAS30560-19-1 (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC, 2004): 1) Not Listed 0.2.21.2 HUMAN OVERVIEW A) At the time of this review, no data were available to assess the carcinogenic potential of this agent. B) The widely used organophosphates are thought not to be carcinogenic; however, controversy exists in this area. 0.2.22 GENOTOXICITY A) Acephate has had variable results in short-term genetic assays for DNA damage and repair, mutagenicity and chromosome aberrations. LABORATORY: A) Monitor vital signs frequently. Institute continuous cardiac and pulse oximetry monitoring. Monitor for respiratory distress (i.e. bronchorrhea, bronchospasm) and for clinical evidence of cholinergic excess (i.e. salivation, vomiting, urination, defecation, miosis). B) Determine plasma and/or red blood cell cholinesterase activities (plasma is generally more sensitive, but red cell correlates somewhat better with clinical signs and symptoms). Depression in excess of 50% of baseline is generally associated with cholinergic effects, in severe poisoning cholinesterase activity may be depressed by 90% of baseline. Correlation between cholinesterase levels and clinical effects in milder poisonings may be poor. C) Obtain serial ECGs. Patients who develop a prolonged QTc interval or PVCs are more likely to develop respiratory insufficiency and have a worse prognosis. D) Monitor electrolytes and serum lipase in patients with significant poisoning. Patients who have increased pancreatic enzyme concentrations are more likely to develop respiratory insufficiency and have a worse prognosis. E) Monitor pulmonary function (i.e. forced vital capacity,

expiratory volume in 1 second, negative inspiratory force) in symptomatic patients, may help anticipate need for intubation. TREATMENT OVERVIEW: 0.4.2 ORAL EXPOSURE A) MANAGEMENT OF MILD TOXICITY 1) A patient who is either asymptomatic or presents with mild clinical symptoms (i.e. normal vitals, pulse oximetry and an acetylcholinesterase greater than 80% of lower reference range), and remains stable for 12 hours can be discharged. Obtain appropriate psychiatric evaluation if an intentional exposure. B) MANAGEMENT OF MODERATE TO SEVERE TOXICITY 1) Immediate assessment and evaluation. Airway management is likely to be necessary. Simple decontamination (i.e. skin and gastrointestinal, removal of contaminated clothes). Administer antidotes: atropine for muscarinic manifestations (e.g. salivation, diarrhea, bronchorrhea), pralidoxime for nicotinic manifestations (e.g. weakness, fasciculations). Treat seizures with benzodiazepines. Admit to intensive care with continuous monitoring, titration of antidotes, ventilation, and inotropes as needed. Consult a medical toxicologist and/or poison center. C) DECONTAMINATION 1) PREHOSPITAL: Activated charcoal and ipecac are contraindicated because of possible respiratory depression and seizures and risk of aspiration. Remove contaminated clothing, wash skin with soap and water. Universal precautions and nitrile gloves to protect personnel. 2) INGESTION: Activated charcoal for large ingestions. Consider nasogastric tube for aspiration of gastric contents, or gastric lavage for recent large ingestions, if patient is intubated or able to protect airway. 3) DERMAL: Remove contaminated clothing. Wash skin thoroughly with soap and water. Universal precautions and nitrile gloves to protect staff from contamination. Systemic toxicity can result from dermal exposure. 4) OCULAR: Copious eye irrigation. D) AIRWAY MANAGEMENT 1) Immediately assess airway and respiratory function. Administer oxygen. Suction secretions. Endotracheal intubation may be necessary because of respiratory muscle weakness or bronchorrhea. Avoid succinylcholine for rapid sequence intubation as prolonged paralysis may result. Monitoring pulmonary function (FVC, FEV1, NIF) may help anticipate need for intubation. E) ANTIDOTES 1) Atropine is used to antagonize muscarinic effects. Oximes (pralidoxime in the US, or obidoxime in some other countries) are used to reverse neuromuscular blockade. Use of oximes is usually indicated for patients with moderate to severe toxicity. a) AUTOINJECTORS: PREHOSPITAL TREATMENT: DuoDote(R) (Meridian Medical Technologies, Columbia, MD) is a

dual chambered device that delivers 2.1 mg atropine and 600 mg pralidoxime in a single needle for intramuscular use. It is intended for use in a civilian/community setting, and is administered by EMS personnel who have been trained to recognize and treat nerve agent or insecticide intoxication. MARK 1 (Meridian Medical Technologies, Columbia, MD) is used by the US military and the autoinjector delivers 2 milligrams atropine/0.7 milliliter and 600 milligrams pralidoxime chloride/2 milliliters into two separate devices for intramuscular use. b) ATROPINE 1) Atropine is used to treat muscarinic effects (e.g. salivation, lacrimation, defecation, urination, bronchorrhea). ADULT: 1 to 3 mg IV; CHILD: 0.02 mg/kg IV. If inadequate response in 3 to 5 minutes, double the dose. Continue doubling the dose and administer it IV every 3 to 5 minutes as needed to dry pulmonary secretions. Once secretions are dried, maintain with an infusion of 10% to 20% of the loading dose every hour. Monitor frequently for evidence of cholinergic effects or atropine toxicity (e.g. delirium, hyperthermia, ileus) and titrate dose accordingly. Large doses (hundreds of milligrams) are sometimes required. Atropinization may be required for hours to days depending on severity. c) PRALIDOXIME 1) Administer for nicotinic effects (i.e. weakness, fasciculations, respiratory failure), generally given to any patient requiring atropine therapy. ADULT: 2 grams IV loading dose over 20 minutes followed by an infusion of 500 to 1000 mg/hr; CHILD: 25 to 50 mg/kg (2 g maximum) loading dose diluted to 5% concentration in NS infuse over 15 to 30 minutes, followed by infusion of 10 to 20 mg/kg/hr. Oximes can usually be stopped 12 hours after atropine is stopped or if butyrylcholinesterase (plasma cholinesterase) is increasing. F) SEIZURES 1) IV benzodiazepines are indicated for seizures or agitation, diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV; repeat as needed. G) HYPOTENSIVE EPISODE 1) IV fluids, dopamine, norepinephrine. H) BRONCHOSPASM 1) Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine. I) PATIENT DISPOSITION 1) HOME CRITERIA: Patients with unintentional trivial exposures who are asymptomatic can be observed in the home or in the workplace. 2) OBSERVATION CRITERIA: Patients with deliberate or significant exposure and those who are symptomatic should be sent to a health care facility for evaluation, treatment and observation for 6 to 12 hours. Onset of toxicity is variable; most patients will develop symptoms within 6 hours. Patients that

3)

4) J) 1) 2) 3) 4)

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3) 4)

L) 1)

2)

remain asymptomatic 12 hours after an ingestion or a dermal exposure are unlikely to develop severe toxicity. However, highly lipophilic agents (like fenthion) can produce initially subtle effects followed by progressive weakness including respiratory failure. Cholinesterase activity should be determined to confirm the degree of exposure. ADMISSION CRITERIA: All intentional ingestions should be initially managed as a severe exposure. Determine cholinesterase activity to assess if a significant exposure occurred. Patients who develop signs or symptoms of cholinergic toxicity (e.g. muscarinic, nicotinic OR central) should be admitted to an intensive care setting. CONSULT CRITERIA: Consult a medical toxicologist and/or poison center for assistance with any patient with moderate to severe cholinergic manifestations. PITFALLS Inadequate initial atropinization. Patients with severe toxicity require rapid administration of large doses, titrate to the endpoint or drying pulmonary secretions. Monitor respiratory function closely, pulmonary function testing may provide early clues to the development of respiratory failure. Some component of dermal exposure occurs with most significant overdoses, inadequate decontamination may worsen toxicity. Patients should be monitored closely for 48 hours after discontinuation of atropine and pralidoxime for evidence of recurrent toxicity or intermediate syndrome. TOXICOKINETICS Well absorbed across the lung, mucous membranes (including gut), and skin; significant toxicity has been reported after all these routes of exposure. Most patients who develop severe toxicity have signs and symptoms within 6 hours of exposure, onset of toxicity is rarely more than 12 hours after exposure. Highly lipophilic organophosphates (e.g. fenthion, disulfoton) may produce subtle early toxicity that can progress to severe weakness/respiratory failure over many hours. Recurrence of toxicity after apparent improvement has been described. Some organophosphates undergo "ageing", a process by which the bond of the organophosphate to acetylcholinesterase becomes stronger, and cannot be reversed readily by oximes. Early oxime administration may prevent aging and shorten clinical manifestations of toxicity. PREDISPOSING CONDITIONS Patients with chronic occupational exposure to organophosphates may have chronically depressed cholinesterase activity and may develop severe toxicity after smaller acute exposures. Dermal absorption is enhanced in young children due to larger surface area to volume ratio and more permeable

skin. M) DIFFERENTIAL DIAGNOSIS 1) Gastroenteritis, food poisoning, asthma, myasthenic crisis, cholinergic excess from medications. 0.4.3 INHALATION EXPOSURE A) Remove from exposure and administer oxygen if respiratory distress develops. B) Inhaled ipratropium or glycopyrrolate may be useful in addition to intravenous atropine for bronchorrhea and bronchospasm. Inhaled beta agonists may be useful for bronchospasm unresponsive to anticholinergics. 0.4.4 EYE EXPOSURE A) Irrigate exposed eyes with water or normal saline. Systemic toxicity is unlikely to develop from ocular exposure alone. 0.4.5 DERMAL EXPOSURE A) OVERVIEW 1) Systemic effects can occur from dermal exposure to organophosphates. Remove contaminated clothing, wash skin thoroughly with soap and water. Use universal precautions and nitrile gloves to protect staff from contamination. 2) Monitor for the development of cholinergic toxicity and treat as in oral exposure. RANGE OF TOXICITY: A) A toxic dose has not been established. The World Health Organization (WHO) has classified acephate, technical grade, as pesticide class III (slightly hazardous). Insufficient data are available to accurately determine the potential risk of acephate to humans. Organophosphates are absorbed across the lung, mucous membranes (including gut), and skin. Poisoning depends upon inherent toxicity, dosage, rate of absorption, rate of metabolic breakdown, and prior exposure to other cholinesterase inhibitors. ANTIDOTE AND EMERGENCY TREATMENT: FIRST AID MEASURES EYES: Hold eye open and rinse slowly and gently with water for 15 to 20 minutes. Remove contact lenses, if present, after the first 5 minutes, then continue rinsing eyes. Call a poison control center or doctor for treatment advice. SKIN: If on skin or clothing, take off contaminated clothing. Rinse skin immediately with plenty of water for 15 to 20 minutes. Call a poison control center or doctor for treatment advice. INGESTION: If swallowed, call a poison control center or doctor immediately for treatment advice. Have person sip glass of water if able to swallow. Do not induce vomiting unless told to by a poison control center or doctor. Never give anything by mouth to an unconscious person.

INHALATION: Move person to fresh air. If person is not breathing, call 911 or an ambulance, then give artificial respiration ... Call a poison control center or doctor for further treatment advice. NOTES TO PHYSICIAN: This material contains a cholinesterase inhibitor. Measurement of blood cholinesterase activity may be useful in monitoring exposure. If signs and/or symptoms of cholinesterase inhibition appear, atropine sulfate is antidotal. ... PROTOPAM is also antidotal and may be used in conjunction with atropine but should not be used alone. /Orthene Fire Ant Killer 1 (50% acephate)/[The Scotts Company; MSDS for Orthene Fire Ant Killer 1. 10 p. (February 21, 2001). Available from, as of February 22, 2007: http://www.ortho.com/index.cfm/event/media.detail/documentId/a270 c9a6c39f3713713f73edeaef2347] **PEER REVIEWED** Airway protection. Insure that a clear airway exists. Intubate the patients and aspirate the secretions with a large-bore suction device if necessary. Administer oxygen by mechanically assisted pulmonary ventilation if respiration is depressed. Improve tissue oxygenation as much as possible before administering atropine, so as to minimize the risk of ventricular fibrillation. In severe poisonings, it may be necessary to support pulmonary ventilation mechanically for several days. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 40] **PEER REVIEWED** Atropine sulfate. Administer atropine sulfate intravenously, or intramuscularly if intravenous injection is not possible. Remember that atropine can be administered through an endotracheal tube if initial IV access if difficult to obtain. ... Atropine does not reactivate the cholinesterase enzyme or accelerate disposition of organophosphate. Recrudescence of poisoning may occur if tissue concentrations of organophosphate remain high when the effect of atropine wears off. Atropine is effective against muscarinic manifestations, but it is

ineffective against nicotinic actions, specifically muscle weakness and twitching, and respiratory depression. Despite the limitations, atropine is often a life-saving agent in organophosphate poisonings. ... The adjunctive use of nebulized atropine has been reported to improve respiratory distress, decrease bronchial secretions, and increase oxygenation. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 41] **PEER REVIEWED** Glycopyrolate has been studied as an alternative to atropine and found to have similar outcomes using continuous infusion. Ampules of ... glycopyrolate were added to ... saline and this infusion was titrated to the desired effects of dry mucous membranes and heart rate above 60 beats/min. During this study, atropine was used as a bolus for a heart rate less than 60 beats/min. The other apparent advantage to this regimen was a decreased number of respiratory infections. ... /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 41] **PEER REVIEWED** Pralidoxime. Before administration of pralidoxime, draw a blood sample (heparinized) for cholinesterase analysis (since pralidoxime tends to reverse the cholinesterase depression). Administer pralidoxime (Protopam, 2-PAM), a cholinesterase reactivator, in cases of severe poisoning by organophosphate pesticides in which respiratory depression, muscle weakness, and/or twitching are severe. When administered early (usually less than 48 hours after poisoning) pralidoxime relieves the nicotinic as well as the muscarinic effects of poisoning. Pralidoxime works by

reactivating the cholinesterase and also by slowing the "aging" process of phosphorylated cholinesterase to a non-reactivatable form. ... Dosage of pralidoxime may be repeated in 1-2 hours, then at 10-12 hour intervals if needed. In very severe poisonings, dosage rates may be doubled. Repeated doses of pralidoxime are usually required. In cases that involve continuing absorption of organophosphate (as after ingestion of large amounts), or continuing transfer of highly lipophilic organophosphate from fat into blood, it may be necessary to continue administration of pralidoxime for several days beyond the 48 hour post-exposure interval usually cited as the limit of its effectiveness. ... Blood pressure should be monitored during administration because of the occasional occurrence of hypertensive crisis. Administration should be slowed or stopped if blood pressure rises to hazardous levels. Be prepared to assist pulmonary ventilation mechanically if respiration is depressed during or after pralidoxime administration. If intravenous injection is not possible, pralidoxime may be given by deep intramuscular injection. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 41] **PEER REVIEWED** Skin decontamination. In patients who have been poisoned by organophosphate contamination of skin, clothing, hair, and/or eyes, decontamination must proceed concurrently with whatever resuscitative and antidotal measures are necessary to preserve life. Flush the chemical from the eyes with copious amounts of clean water. If no symptoms are evident in a patient who remains alert and physically stable, a prompt shower and shampoo may be appropriate, provided the patient is carefully observed to insure against any sudden appearance of poisoning. If there are any indications of weakness, ataxia, or other neurologic impairment, clothing

victim should

should be removed and a complete bath and shampoo given while the is recumbent, using copious amounts of soap and water. Attendants

wear rubber gloves as vinyl provides no protection against skin absorption. Surgical green soap is excellent for this purpose, but ordinary soap is about as good. Wash the chemical from skin folds and from under fingernails. Contaminated clothing should be promptly removed, bagged and laundered before returning. Contaminated leather shoes should be discarded. Note that the pesticide can contaminate the inside surfaces of gloves, boots, and headgear. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 43] **PEER REVIEWED** Gastrointestinal decontamination. If organophosphate has been ingested in quantities probably sufficient to cause poisoning, consideration should be given to gastrointestinal decontamination ... . If the patient has already vomited, which is most likely in serious exposures, further efforts at GI decontamination may not be indicated. In significant ingestions, diarrhea and/or vomiting are so constant that charcoal adsorption and catharsis are not indicated. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Observation. Observe patient closely for at least 72 hours to ensure that symptoms (sweating, visual disturbances, vomiting, diarrhea, chest and abdominal distress, and sometimes pulmonary edema) do not recur as atropinization is withdrawn. In very severe poisonings by ingested organophosphates, particularly the more lipophilic and slowly hydrolyzed

compounds, metabolic disposition of toxicant may require as many as 5-14 days. In some cases, this slow elimination may combine with profound cholinesterase inhibition to require atropinization for several days or even weeks. As dosage is reduced, the lung bases should be checked frequently for crackles. If crackles are heard, or if there is a return of miosis, bradycardia, sweating, or other cholinengic signs, atropinization must be re-established promptly. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Furosemide may be considered if pulmonary edema persists in the lungs even after full atropinization. It should not be used until the maximum benefit of atropine has been realized. Consult package insert for dosage and administration. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Pulmonary ventilation. Particularly in poisonings by large ingested doses of organophosphate, monitor pulmonary ventilation carefully, even after recovery from muscarinic symptomatology, to forestall respiratory failure. In some cases, respiratory failure has developed several days following organophosphate ingestion, and has persisted for days to weeks. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at:

http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Hydrocarbon aspiration may complicate poisonings that involve ingestion of liquid concentrates of organophosphate pesticides. Pulmonary edema and poor oxygenation in these cases will not respond to atropine and should be treated as a case of acute respiratory distress syndrome. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Cardiopulmonary monitoring. In severely poisoned patients, monitor cardiac status by continuous ECG recording. Some organophosphates have significant cardiac toxicity. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 44] **PEER REVIEWED** Seizure control. Rarely, in severe organophosphate poisonings, convulsions occur despite therapy with atropine and pralidoxime. Insure that causes unrelated to pesticide toxicity are not responsible: head trauma, cerebral anoxia, or mixed poisoning. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 45] **PEER REVIEWED** Contraindications. The following drugs are contraindicated in nearly all organophosphate poisoning cases: morphine, succinylcholine, theophylline,

phenothiazines, and reserpine. Adrenergic amines should be given only if there is a specific indication, such as marked hypotension. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 45] **PEER REVIEWED** Re-exposures. Persons who have been clinically poisoned by organophosphate pesticides should not be re-exposed to cholinesterase inhibiting chemicals until symptoms and signs have resolved completely and blood cholinesterase activities have returned to at least 80 percent of pre-poisoning levels. If blood cholinesterase was not measured prior to poisoning, blood enzyme activities should reach at least minimum normal levels before the patient is returned to a pesticide contaminated environment. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 45] **PEER REVIEWED** Do not administer atropine or pralidoxime prophylactically to workers exposed to organophosphate pesticides. Prophylactic dosage with either atropine or pralidoxime may mask early signs and symptoms of organophosphate poisoning and thus allow the worker to continue exposure and possibly progress to more severe poisoning. Atropine itself may enhance the health hazards of the agricultural work setting: impaired heat loss due to reduced sweating and impaired ability to operate mechanical equipment due to blurred vision. This can be caused by mydriasis, one of the effects of atropine. /Organophosphate pesticides/[U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances.

Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 45] **PEER REVIEWED** Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Aggressive airway control may be needed. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Organophosphates and related compounds/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 294] **PEER REVIEWED** Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously and consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer atropine. Correct hypoxia before giving atropine ... . Administer pralidoxime chloride (2 PAM). USE UNDER DIRECT PHYSICIAN ORDERS ONLY ... . Treat

seizures with adequate atropinization and correction of hypoxia. In rare cases diazepam or lorazepam may be necessary ... . Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organophosphates and related compounds/ [Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 294-5] **PEER REVIEWED** ANIMAL TOXICITY STUDIES: EVIDENCE FOR CARCINOGENICITY: CLASSIFICATION: C; possible human carcinogen. BASIS FOR CLASSIFICATION: The classification is based on increased incidence of hepatocellular carcinomas and adenomas in female mice. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Limited.[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS). Summary on Acephate (30560-19-1). Available from, as of March 15, 2000: http://www.epa.gov/iris/] **PEER REVIEWED** Cancer Classification: Group C Possible Human Carcinogen[USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for Carcinogenic Potential" (April 2006)] **QC REVIEWED** NON-HUMAN TOXICITY EXCERPTS: /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats were administered the organophosphorus insecticide acephate at 1.0 or 10.0 mg/kg/day for 15 weeks. ... No significant inhibition in the activity of brain acetylcholinesterase was noted at doses of 1.0 or 10.0 mg/kg/day. Low levels of acephate exposure (1.0 mg/kg/day), which did not alter plasma cholinesterase or RBC acetylcholinesterase activity levels, resulted in a significant elevation of plasma epinephrine and norepinephrine levels. Decreased GABA, dopamine, and tyrosine levels and glutamic acid decarboxylase activity were observed in brains of these rats. Similar changes occurred in rats exposed to 10 mg of acephate/kg/day; however, plasma cholinesterase and RBC acetylcholinesterase activities were inhibited.[Singh AK, Drewes LR;

Environ Res 43 (2): 342-9 (1987)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3608937" target=new>PubMed Abstract /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Thirty Sprague-Dawley rats/sex/group were dosed orally in the diet with 0, 5, 50 or 700 ppm of ORTHENE Technical (purity: 99.0%) for up to 13 weeks ((M): 0, 0.33, 3.31, 48.63 mg/kg/day, (F) 0, 0.41, 3.95, 58.27 mg/kg/day). There were no treatment-related effects upon mean body weights or food consumption. ... The mean cholinesterase (ChE) activity levels for plasma were lower than that of the control at 3 weeks for the 50 ppm males and females (p < 0.05 or p < 0.01) and at 3, 7 and 13 weeks for the 700 ppm males and females (p < 0.01). The mean red blood cell activity levels were less at 3, 7 and 13 weeks for the 700 ppm males (p < 0.01) and at 3 and 7 weeks for the 700 ppm females (p < 0.05 or p < 0.01). In the 6 subregions of the brain for which ChE activity was assayed, the activity levels were less than that of the control at 50 ppm and above for all of the regions at least twice for the 3 time points assayed (p < 0.1). The mean percent of control activity for the 50 ppm males ranged from 50.6% in the cortex (week 13) to 75.8% in the cerebellum (week 13). For the 50 ppm females, the percent of control activity ranged from 45.4% in the hippocampus (week 13) to 81.5% in the brainstem (week 3). For the 5 ppm treatment group males , ChE activity was reduced in the hippocampus (week 3, p < 0.01, 86.1% of control), midbrain (weeks 3, 7,13, p < 0.01, 85.5 to 90.5%), brainstem (weeks 3, 7, 13, p < 0.01, 85.0 to 90.6%), cerebellum (week 3, p < 0.01, 89.1%), and cortex (weeks 3, 7, 13, p < 0.01, 82.4 to 89.9%). Similarly, for the 5 ppm females, ChE activity was less in the hippocampus (week 13, p < 0.01, 71.6% of control), olfactory lobe (weeks 7, 13, p < 0.05, 75.7, 82.2%), midbrain (weeks 3, 7, 13, p < 0.1 or p < 0.05, 80.9 to 91.0%), cerebellum (week 7, p < 0.1, 83.9%) and cortex (week 13, p < 0.01, 86.2%). No treatment related effects were noted in the histopathological examination. Possible adverse effect: significant brain ChE inhibition; NOEL (Clinical Signs):

(M/F) 700 ppm ((M): 48.63 mg/kg/day, (F): 58.27 mg/kg/day) (based upon the lack of treatment effects in the FOB determinations for the 700 ppm group); NOEL (ChE Inhibition): < 5 ppm ((M): < 0.33 mg/kg/day, (F) < 0.41 mg/kg/day) (based upon significant brain ChE inhibition at 5 ppm).[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Acephate (purity = 92.7, 92.1%) was fed in the diet to CD1 mice for 104 weeks at 0 (vehicle = chow), 50, 250 or 1000 ppm (7, 36 or 146 mg/kg/day) for males; 8, 42, or 167 mg/kg/day for females) with 75/sex/group). Possible adverse effect. Nominal NOEL = 50 ppm (decreased body weight at mid and high doses; hepatocellular carcinoma, adenoma and hyperplasia were observed in females at the high dose. Other dose-related non-neoplastic changes in males and females were observed primarily at mid- and high-doses. Microscopic lung changes were observed at all dose levels in both sexes but were not well defined ("pigmented alveolar macrophages", "eosinophilic foreign bodies"). ...[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Acephate technical, purity of 99.9%, was administered in the feed at concentrations of 0, 10, 120 (reduced from 200 ppm during week 2

of

study), or 800 ppm to 5 Beagle dogs/sex/group for 1 year. Highdose groups had lower red cell mass indices, elevated /Activated Partial Thromboplastin Time/ and increased liver weights. Liver pathology (perivascular pleocellular infiltrate and pigment in the reticuloendothelial cells) was noted in most high-dose animals and one mid-dose male (NOEL = 10 ppm/day). Significant RBC cholinesterase (ChE)

inhibition for mid and high dose groups was reported in addition to brain ChE inhibition for midand high dose females and all dose levels for males. ChE NOEL (females) = 10 ppm; males < 10 ppm. Possible Adverse Effect: Significant brain ChE inhibition (no NOEL in males).[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Lifetime Oral Toxicity/Carcinogenicity Study ... Acephate (92.4%) fed in the diet /of rats/ at 0, 5, 50 or 700 ppm (0.24/0.31, 2.44/3.06 or 38.2/47.2 mg/Kg, M/F), 80/sex/group; significantly lower body weight in males at high dose; consistent cholinesterase inhibition at high dose and to a lesser extent at low and mid dose levels; systemic NOEL = 5.0 ppm (based on brain cholinesterase).[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In 2 year feeding trials: dogs showed depression of cholinesterase at 100 mg/kg diet (maximum dose level) but no other significant effect; rats showed depression of cholinesterase but no effect on weight gain nor pathological effect at 30 mg/kg diet. No teratogenic, mutagenic or carcinogenic effect was observed.[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987., p. 10] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Acephate technical (purity = 99.5%, or purity = 98.7%) was administered to mated ... rats (25/dose) by gavage on days 6 - 15 of presumed gestation (presence of vaginal sperm or copulatory plug = day 0 of gestation) at 0,

5, 20 or 75 mg/kg/day. Maternal NOEL = 5 mg/kg (increase in tremors, decrease in motor activity, body weight and food consumption). Developmental NOEL = 20 mg/kg (decreased fetal body weight, and delay in ossification of hindpaw phalanges-historical controls for malformations and alterations were provided in the report). /Acephate technical/[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Chevron acephate technical, 98.5%, was fed in the diet to Crl:COBS CD (SD) BR rats, 30/sex/group, at 0, 25, 50 or 500 ppm for two generations, 2 litters/generation, and one litter in the third generation. Parental NOEL = 50 ppm (soft/liquid feces), Reproductive NOEL = 50 ppm (reduced litter size and postnatal survival). ...[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Acephate (92.8%) given by oral gavage /to rabbits/ at 0, 1, 3 or 10 mg/kg/day on days 6-27 of gestation, not adjusted for purity, with 16 per group. No significant developmental effects. Slight maternal toxicity at high dose. Developmental NOEL = > 10 mg/kg, maternal NOEL = 3 mg/kg. ... [California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Presumed pregnant Crl:CD7(SD)IGS BR VAF/Plus7 female rats were given doses of 0 (water), 0.5, 1 or 10 mg/kg/day, gestation days 6 through termination of

pregnancy and days 0 through 6 of lactation. Pups were dosed at these same doses beginning day 7 of lactation through weaning at day 21. There were 25 dams per dose with 20 litters selected for continuation of the study. There were 5 subsets of pups with 1/sex/litter when possible per subset. Subset 1 were sacrificed on PND 21 for neurohistological examination or ChE assays. Subset 2 were sacrificed on PND 71 following evaluation of passive avoidance and watermaze testing. Subset 3 were sacrificed on PND 71 following testing for motor activity (days 13, 17, 21 and 58) and auditory startle habituation (days 22 and 62). Subset 4 were examined outside of the home cage on days 4, 11, 21, 35, 45 and 60 for abnormal signs and sacrificed on PND 71 for neurohistological examination. Subset 5 were sacrificed on PND 21 and were used to standardize litter size and for ChE assays. Litters were standardized to 10/litter on PND 4 with extra pups being used for ChE assays (plasma, RBC and brain). All parental dams survived with no adverse clinical signs. Body weights, weight gains, food consumption and necropsy findings were comparable among groups. Acephate did not affect sexual maturation, learning, motor activity or weight of pups. Administration from gestation day 6 through lactation day 4 did not affect brain, plasma or RBC cholinesterase activity on PND 4. Direct dosing from lactation day 7 through day 21 did result in a statistically significant and biologically relevant reduction in all three measurements at 10 mg/kg/day, PND 21. At 0.5 and 1 mg/kg, brain ChE was reduced > 20%, being significant in male pups (-28.7% and 33.7%) and in sexes combined but not in females (-25.4% and -25.8%). Plasma and RBC cholinesterase activities were lower at 0.5 and 1 mg/kg but not clearly dose-related. No affects on brain weight, neuromorphometric or neurohistopathology were noted. Systemic NOAEL = 10 mg/kg/day with brain ChE NOEL < 0.5 mg/kg/day when given directly to pups. [California Environmental Protection Agency Department of Pesticide Regulation;

of

Acephate Summary of Toxicological Data (1986). Available from, as

February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Neurotoxicity/ Thirty Sprague-Dawley rats/sex/group were treated in the diet with 0, 2, 5, 10 or 150 ppm of Orthene Technical (purity: 98.2%) for up to 13 weeks ((M), 0, 0.12, 0.28, 0.58, or 8.90 mg/kg/day, (F) 0, 0.15, 0.36, 0.76 or 11.48 mg/kg/day). Ten animals/sex/group were euthanized after 4, 9 and 13 weeks on study. There were no mortalities during the study. There were no treatmentrelated clinical signs or effects on food consumption. There was no apparent treatment-related effect on body weight gain. Significant brain cholinesterase (ChE) inhibition was noted for the 5 ppm group and above for both sexes after 4, 9 and 13 weeks of treatment (p < 0.01) (% of control activity: 5 (M) 92.5 to 92.7%, (F) 89.3 to 91.2%, 10 (M) 85.8 to 89.1%, (F) 83.1 to 88.5%, 150 (M) 48.3 to 52.7%, (F) 45.2 to 54.0%). For the 2 ppm treatment group, only the females demonstrated significant brain ChE inhibition at all of the time points (p < 0.01) (% of control activity: 90.3 to 91.9%). A dose-response for ChE inhibition in the plasma and red blood cells was not well demonstrated with statistical significance only at the 150 ppm treatment level. The necropsy examination did not reveal any treatment-related lesions. Possible adverse effect: inhibition of brain cholinesterase; NOEL: (M) 2 ppm (0.12 mg/kg/day) (based upon significant brain ChE inhibition in the 5 ppm treatment group, (F) < 2 ppm ( < 0.15 mg/kg/day) (based on the significant brain ChE inhibition in the 2 ppm treatment group).[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Neurotoxicity/ Acephate (98%) at 785 mg/Kg, redosed after 21 days, 5 mg/kg atropine to protect at dosing with additional

atropine given /to chickens/ over 21 hours; 6 hens in control groups and 12 in treatment group; triortho cresyl phospahte (TOCP) positive control; no delayed neurotoxicity noted.[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** by /LABORATORY ANIMALS: Neurotoxicity/ Acephate (98.9%) at 375 mg/Kg

gavage /to chickens/, one dosing, 5 mg/kg atropine to protect; 12 hens in control groups and 24 in treatment group; triortho cresyl phospahte (TOCP) positive control; no delayed neurotoxicity noted.[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /LABORATORY ANIMALS: Neurotoxicity/ Thirty Sprague-Dawley rats/sex/group were dosed by oral gavage with 0, 10, 100 or 500 mg/kg of Orthene Technical (purity: 99.0%). Twelve animals/sex/group were evaluated in the Functional Observational Battery (FOB) and for locomotor activity as well as in the neuropathology examination. The other 18 animals/sex/group were euthanized for cholinesterase (ChE) activity evaluation, 6 animals/sex/group at 2.5 hours and 7 and 14 days post-dose. No animals died as a result of the treatment. The mean body weight for the males in the 500 mg/kg group was less than that of the controls at 7 days post-dose (p < 0.05). Clinical signs included whole body tremors, repetitive movement of the mouth, tremors of the forelimbs and/or hindlimbs, and alterations in the posture/gait of the animals in the 100 and 500 mg/kg groups in a dose-related manner. The earliest observation of these signs was at 30 minutes and the time to peak effect was between 2 and 2.5 hours and persisted up to 8 hours post-dose in the high dose group. The signs were no longer present by the next day. Salivation, lacrimation and

chromodaccryorrhea was observed only in the 500 mg/kg animals. In the FOB, at 2.5 hours post-dose, the 100 and 500 mg/kg animals exhibited in a dose-related manner, abnormal posture, whole body tremors which ranged from slight to extremely coarse, slightly impaired to totally impaired mobility, walking on tiptoes to ataxia, decreased arousal and rearing, diminished response to a tail pinch, impaired righting reflex, and reduced body temperature. In addition, the high dose animals exhibited signs of lacrimation, salivation, poor grooming, diminished startle, touch and approach responses and catalepsy. The males in the high dose group had no pupilary response. The hindlimb extensor strength was reduce for the males in both the 100 and 500 mg/kg groups and the females in the 500 mg/kg group. The fore and hindlimb grip strength for the high dose males was reduced from that of the controls (p < 0.01 and p < 0.05, respectively). The rotorod performance was affected in all of the male treatment groups (p < 0.01) and for the high dose females (p < 0.01). In the motor activity evaluation, total activity and ambulatory activity counts were reduced for the animals in the 100 and 500 mg/kg groups. All of these parameters had returned to normal by day 7. In the ChE activity determinations, all of the treatment groups for both sexes exhibited reduced activity levels in the plasma, red blood cells and subregions of the brain at 2.5 hours post-dose (p < 0.01). At 7 days postdose, reduced activity was still evident in the following tissues: hippocampus, females, 500 mg/kg; midbrain, males, 500 mg/kg, females, 500 mg/kg; brainstem, males and females, 500 mg/kg; cerebellum, males and females, 500 mg/kg; cortex, males, 500 mg/kg, females, 10, 100, 500 mg/kg (p < 0.05 or p < 0.01). At 14 days, activity was reduced in the red blood cells and the midbrain of the 500 mg/kg males (p < 0.05 and p < 0.01, respectively). No treatment related lesions were evident in the neuropathology examination. Possible Adverse effect: extensive neurtoxic signs; NOEL(clinical signs) (M/F): 10 mg/kg (based upon the clinical signs

manifested by the 100 mg/kg treatment animals); NOEL (cholinesterase inhibition): < 10 mg/kg (based upon ChE inhibition evident in the plasma, red blood cells and subregions of the brain of the 10 mg/kg treatment group).[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /GENOTOXICITY/ Acephate (92.41%) was tested at 0.001 to 10 ug/plate with Salmonella strain TA100 and at 1, 2 and 10 ug/plate with strains TA98 and TA1537, with and without rat liver S9. There were 2 plates/dose level. Results indicated weak mutagenic activity in TA100 with and without activation.[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /GENOTOXICITY/ ... Results from in vitro assays /of acephate technical/ have ranged from negative to weakly positive; acephate technical is apparently a direct acting agent in these tests. However, expressed in terms of molar potency, acephate technical has generally been at least 100-1000 times less potent than known positive mutagens tested in vitro. Following in vivo exposure at maximum tolerated doses, acephate technical did not induce chromosomal aberrations, sister chromatid exchange, or micronuclei in mouse bone marrow cells; a dominant lethal study in mice was also negative. In a supplemental study, no induced chromosomal aberrations or sister chromatid exchange could be detected in lymphocytes from a pair of cynomolgus monkeys following exposure to acephate technical at a low dose level for 20 days. At dose levels limited by toxicity, no positive results were observed for induction of sex-linked, recessive lethality in Drosophilla melanogaster.[Carver JH et al; Toxicology 35 (2):

125-42 (1985)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3890268" target=new>PubMed Abstract /GENOTOXICITY/ Two organophosphorus (OP) pesticides (chloropyriphos and acephate) and cyclophosphamide (CP) (positive control) were tested for their ability to induce in vivo genotoxic effect in leucocytes of Swiss albino mice using the single cell gel electrophoresis assay or comet assay. The mice were administered orally with doses ranging from 0.28 to 8.96 mg/kg body weight (bwt) of chloropyriphos and 12.25 to 392.00 mg/kg bwt. of acephate. The assay was performed on whole blood at 24, 48, 72 and 96 hr. A significant increase in mean comet tail length indicating DNA damage was observed at 24h post-treatment (P < 0.05) with both pesticides in comparison to control. The damage was dose related. The mean comet tail length revealed a clear dose dependent increase. From 48 hr post-treatment, a gradual decrease in mean tail length was noted. By 96 hr of post-treatment the mean comet tail length reached control levels indicating repair of the damaged DNA.[Rahman MF et al; Mutat Res 516 (1-2): 139-47 (2002)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11943619" target=new>PubMed Abstract /GENOTOXICITY/ The genotoxic potential of asataf (acephate) was evaluated by a battery of in vivo tests: bone marrow chromosome aberrations, micronucleus, sperm-shape abnormality and dominant lethal tests in mice. A significant enhancement in the percentage of chromosome aberrations was noticed in 3 doses, 3 routes and 3 hr after asataf treatment of groups of mice as well as in chronic (sub-acute) treatment. A significant difference in the occurrence of micronuclei was found only at the highest dose whereas all the results of the sperm-shape abnormality test were highly significant. In the dominant lethal mutagenicity assay only the result (dead implants) of a single week (3rd) with the higher dose differed

significantly from control.[Behera BC and Bhunya SP; Mutat Res 223 (3): 287-93 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2739684" target=new>PubMed Abstract /GENOTOXICITY/ Acephate (technical 98.7%) was tested at 2429, 3071, 3714, 4357 and 5000 ug/plate +/- rat liver S9 on mouse lymphoma cells (L5178Y). There were 6 platings/dose level, 4 hour exposure, 48 hr expression time. A dose-dependent increase in mutation frequency over entire dose range +/S9.[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /GENOTOXICITY/ Acephate (99%) given in the diet for five days at 0, 50, 500 and 1000 ppm to CD-1 mice for a dominant-lethal assay; 12 /treated/ males and 192 /untreated/ females/group, 2 females:male for 8 weeks of mating, positive control included ...[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /GENOTOXICITY/ Acephate (98.7%) given by oral gavage in a single dose at 0, 11.2, 37.3 and 112 mg/Kg to Swiss white mice for a bone marrow cytogenetic assay; 4/sex/group, positive control included; clinical signs of toxicity reported; dose selection based on acute toxicity studies included with the report ...[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** /GENOTOXICITY/ Acephate (93.5%) tested at 0.1 to 72 ug/mL without S9 (Exp. #1), 125 to 2000 ug/ml without S9, 0.1 to 1000 ug/mL with rat liver S9 and

in UDS

250 to 4000 ug/mL with contact-inhibited WI-38 human fibroblasts

assay; 3 hour exposure without activation and 1 hour with activation; hydroxyurea to block semiconservative DNA synthesis; DNA was extracted, DNA determined by diphenylamine reaction and tritium quantitated by liquid scintillation counting; in the absence of activation, slight increase in UDS at and above 1000 ug/mL. ...[California Environmental Protection Agency Department of Pesticide Regulation; Acephate Summary of Toxicological Data (1986). Available from, as of February 06, 2007: http://www.cdpr.ca.gov/docs/toxsums/pdfs/1685.pdf] **PEER REVIEWED** ECOTOXICITY EXCERPTS: /BIRDS and MAMMALS/ The purpose of this study was to examine the effects of diazinon and acephate applications to ornamental trees on the breeding behavior and productivity of the American robin and to measure the effect of repeated chlorpyrifos spraying on robin productivity. No cases of adult or juvenile mortality were recorded, and nestling production was not affected. Plasma cholinesterase (ChE) activity in females exposed to diazinon or acephate was significantly lower than that in controls. However, there were no pronounced changes in parental care. The absence of a significant impact on behavior despite the marked change in plasma ChE levels may have been due /to/ one of several factors, i.e. (1) the insecticide had not reached the brain 18 to 24 hr after spraying, and (2) exposure was insufficient to produce behavioral changes. The use of diazinon and acephate on ornamental trees should not be harmful to robins.[DeCarie R et al; Environ Pollut 80 (3): 231-8 (1993)]

/BIRDS and MAMMALS/ American kestrels (F. sparverius) were given a single acute dose of the insecticide acephate (50 mg/kg), alone or superimposed on a moderate background level of DDE (35 ppm wet wt in carcass homogenates). The combined DDE-acephate treatment was chosen to resemble exposure conditions for wild avian predators whose tissues may contain appreciable sublethal accumulations of organochlorine insecticides.

Acephate produced similar cholinesterase (ChE) depression in both groups (39% median depression of serum ChE, 25% median brain ChE depression). Predatory vigilance and attack behavior, measured by frequency and speed of responses to a familiar moving prey model, were not altered by acephate administration in either group. DDE or acephate at these low dosages did not have appreciable effects on kestrels' responses to a prey stimulus with which they had extensive prior contact.[Rudolph SG et al; Arch Environ Contam Toxicol; 13 (3) 367-72 (1984)]

/BIRDS and MAMMALS/ The calculated, acute oral LD50 of acephate and methamidophos to dark-eyed juncos (Junco hyemalis) was 106 mg/kg and 8 mg/kg, respectively. Brain cholinesterase (ChE) activity in birds that died after acephate poisoning was depressed 80% below that of control birds. Birds that died of acute methamidophos poisoning had brain ChE depression of 60%. The birds killed by acephate had brain acephate residue concentrations > 2 mg/kg and methamidophos concentrations usually > 0.25 mg/kg. Eighty percent of the birds killed with methamidophos had brain methamidophos concentrations > 0.1 mg/kg. The 5-day feeding LC50 for acephate was 1,485 mg/kg. Brain ChE activities of birds which died early in the study were less depressed (51.5%) than those which died at a later date (69.6%). Brain residues of acephate and methamidophos were lower in these birds than in the birds of the acute oral LD50 studies. Brain ChE activity returned to normal within 3 days after the birds received a single sublethal dose of acephate. These studies indicate that the amount of acephate needed to produce the ChE depression, found in other investigations in most dark-eyed juncos exposed to forest applications of insecticide, is about 20% of the LD50; however, in a few birds the ChE activity may be depressed to near lethal levels. [Roberts RB et al; Arch. Environ. Contam. Toxicol 10 (2): 185-92 (1981) (9 References)] **PEER REVIEWED** /BIRDS and MAMMALS/ The toxicity of acephate was examined in albino CD1-mice, white-footed-mice, and voles. The estimated median lethal dose in the three species of rodents was 351, 380, and 321 milligrams per kilogram (mg/kg), respectively. Animals were dosed orally with 150, 197,

259, 341, and 449 mg/kg acephate and observed for 7 days in experiment 1. In experiment 2, 0, 25, 100, and 400 parts per million (ppm) acephate in mash was provided ad-libitum for 5 days. In experiment 3, animals were provided mash containing 0 or 400 ppm acephate ad-libitum for 5 days. To monitor the recovery of cholinesterase activity, mash containing 400 ppm acephate was replaced with control feed on day 5. The animals were sacrificed and blood, brain, and liver parameters were measured. In experiment 1, observations for signs of intoxication, mortality, and apparent recovery were made and onset of these signs was found to be dose dependent. Brain acetylcholinesterase activity was reduced in experiment 2. Liver parameters were not affected. Plasma cholinesterase activity was in general highest in laboratory mice, intermediate in voles, and lowest in white-footed-mice at each dietary concentration of acephate. In experiment 3, following dietary exposure to acephate after 14 days of recovery, acetylcholinesterase activity was 81 to 88 percent of control values. The authors suggest that all three types of rodents are equally sensitive to acephate when maintained under relatively similar and constant laboratory conditions. Differences in behavior, eating habits, and habitat could affect routes and degree of exposure and thus render some species of small mammals more vulnerable to organophosphorus insecticides in the field.[Rattner BA and Hoffman DJ; Arch Environ Contam Toxicol 13 (4): 483-91 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6380419" target=new>PubMed Abstract /AQUATIC SPECIES/ The 96 hr LC50 of acephate, a water-soluble organophosphorus insecticide, averaged 2,740 ppm for rainbow trout. ... Uptake of acephate by trout from water was rapid and reached equilibrium concentrations (4 to 6% of ambient concentrations) in 5 to 8 days. Methamidophos, a metabolite of acephate, formed rapidly, reaching > 5% of the acephate concentrations in the fish. Elimination of 50% acephate and methamidophos from rainbow trout required 1.73 to 2.43 days. Acephate or methamidophos were not bioconcentrated in the trout (mean BCF

(bioconcentration factor) = 0.0533). Predictions of bioconcentration of acephate, based on its water solubility, its octanol/water partition coefficient or based on relationships developed in other studies, did not, as a rule, agree with experimental results.[Geen GH et al; J Environ Sci Health Part B Pestic Food Contam Agric Wastes 19 (2): 131-56 (1984)] **PEER REVIEWED** /AQUATIC SPECIES/ Toxicity testing of two organophosphate insecticides, acephate and fenitrothion, was carried out using rainbow trout, with emphasis on the effects of temperature. The LC50 values for both insecticides were determined at three temperatures: 8 deg (cold stress), 15 deg and 22 deg (heat stress). In studies on the physiological mechanisms of organophosphate insecticide toxicity, buccal catheters, dorsal aorta cannulas, and electrocardiogram electrodes were implanted prior to exposure of the fish to acephate at 2000 mg/L or fenitrothion at 2 mg/L. Cholinesterase activities were determined in erythrocytes, serum, brain, gill, heart, and skeletal muscle. Results indicated that the LC50 values of acephate were approximately 600-1000 times higher than those of fenitrothion. Acephate toxicity was not affected by temperature, but the median survival time values for fenitrothion decreased as the test temperature increased. Heart rate was decreased and ventilation rate and buccal amplitude increased by both insecticides. Cough frequency was increased by fenitrothion, but not by acephate. Cholinesterase activity was inhibited in erythrocytes, gill, heart and serum after 3 hr exposure to acephate and after 1 hr exposure to fenitrothion. This study indicates that the cardiovascular and respiratory systems are important sites of action for organophosphate toxicity in fish.[Duangsawasdi M and Klaverkamp JF; ASTM STP 667: 35-51 (1979)] **PEER REVIEWED** /AQUATIC SPECIES/ The effects of acephate, a water-soluble organophosphorus insecticide, on the early growth and survival of salamander, A. gracile, were examined. The 96 hr LC50 for 69-day-

the old

larvae was 8,816 mg/L. Exposure of egg masses to concentrations up to 798 mg/L did not produce significant differences in mortality up to the time of hatching. Larval mortality in the first 7 days after hatching increased at the higher acephate concentrations but declined in the period 7 to 29 days to low rates independent of acephate concentration. Growth rate decreased and morphological abnormalities increased in larvae exposed to 382 and 798 mg/L acephate. This component of lake fauna would be little affected by insect control programs which use acephate since maximum surface water concentrations would probably be < 1 mg/L.[Geen GH et al; J Environ Sci Health Part B Pestic Food Conatm Agric Wastes 19 (2): 157-70 (1984)] **PEER REVIEWED** the C to /AQUATIC SPECIES/ The freshwater mussel Elliptio complanata and Asiatic clam Corbicula fluminea were exposed for 96 hr at 21 deg

aldicarb, a carbamate pesticide, and acephate, an organophosphate pesticide. Test pesticide concentrations ranged from 0 to 320 mg/L. We found no mortality under these conditions. Relative to controls, cholinesterase (ChE) activity in adductor muscle from E. complanata was significantly depressed at concentrations as low as 0.1 mg aldicarb/L and 1.3 mg acephate/L. Higher pesticide concentrations were required to inhibit ChE activity in whole bodies of C. fluminea than in adductor muscle of E. complanata. Raising the experimental temperatures from 21 to 30 deg C increased pesticide-induced mortality, with mussels dying at aldicarb or acephate concentrations of only 5 mg/L. Cholinesterase activities of adductor muscle depressed 94 to 96% relative to controls began to recover within 2 and 12 days, but they were not fully recovered for 12+ and 24+ days following aldicarb and acephate exposures. Both aldicarb and acephate at 5 mg/L reduced shell closure responsiveness of mussels, with more pronounced effects observed at 27 deg C than at 21 deg C. Our data support the usefulness of determining ChE activity in adductor muscle to identify the exposure of freshwater mussels to ChEinhibiting

pesticides.[Moulton CA et al; Environ Toxicol Chem 15 (2): 131-7 (1996)] **PEER REVIEWED** /AQUATIC SPECIES/ Acetylcholinesterase (AChE) activity was measured in Daphnia magna that had been exposed to four organophosphates (OPs; parathion, chlorpyrifos, malathion, and acephate) and one carbamate (propoxur) for 48 h. These results were related to acute toxicity (median effective concentration [EC50] for immobility). For the four OPs, the EC50s were 7.03 pM, 3.17 pM, 10.56 pM, and 309.82 uM, respectively. The EC50 for propoxur was 449.90 pM. Reduction in AChE activity was directly related to an increase in immobility in all chemicals tested. However, the ratio between the EC50 and the AChE median inhibiting concentration ranged from 0.31 to 0.90. A 50% reduction in AChE activity generally was associated with detrimental effects on mobility. However, for acephate, high levels of AChE inhibition (70%) were observed in very low concentrations and were not associated with immobility. In addition, increasing the concentration of acephate further had a slight negative effect on AChE activity but a strong detrimental effect on mobility. Binding sites other than AChE possibly are involved in acephate toxicity to D. magna. Our findings demonstrate different associations between AChE inhibition and toxicity when different chemicals are compared. Therefore, the value of using AChE activity as a biomarker in D. magna will be dependent on the chemical tested.[Printes LB, Callaghan A; Environ Toxicol Chem 23 (5): 1241-7 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15180375" target=new>PubMed Abstract /OTHER TERRESTRIAL SPECIES/ Toxicity of acephate to both Phytoseiulus persimilis Athias-Henriot, a mite predator, and Tetranychus urticae Koch, was measured in a series of experiments. Acephate was more toxic to P. persimilis than T. urticae, regardless of application method, and significant toxicity occurred via food-chain effects. Acephate application as soil drenches of 75, 150 and 300 ppm were more toxic by this route than

foliar sprays, in some cases killing nearly all P. persimilis feeding on T. urticae 21 days after application. Acephate's usefulness in an IPM program involving P. persimilis will be limited by this toxicity, especially if applied to the soil.[Lindquist RK and Wolgamott ML; Environ Entomol 9 (4)L 389-92 (1980)] **PEER REVIEWED** /FIELD STUDIES/ Migratory white-throated sparrows (Zonotrichia albicollis) were exposed to acephate (acetylphosphoramidothioic acid O,Sdimethyl ester), an organophosphorus pesticide, to determine its effects on migratory orientation and behavior. Birds were also exposed to polarizer sheets to determine the mechanism by which acephate may affect migratory orientation. Adult birds exposed to 256 ppm acephate a.i. were not able to establish a preferred migratory orientation and exhibited random activity. All juvenile treatment groups displayed a seasonally correct southward migratory orientation. /The authors/ hypothesize that acephate may have produced aberrant migratory behavior by affecting the memory of the migratory route and wintering ground. This experiment reveals that an environmentally relevant concentration of a common organophosphorus pesticide can alter migratory orientation, but its effect is markedly different between adult and juvenile sparrows.[Vyas NB et al; Environ Toxicol Chem 14 (11): 1961-5 (1995)] **PEER REVIEWED** /FIELD STUDIES/ Understanding the non-target effects of pesticides used in crop production systems is essential for the development of IPM programs in those systems. Two organophosphates for control of citrus thrips (Scirtothrips citri) in citrus were compared at commercial field rates in a lemon orchard for their effect against a predacious mite and a parasitic wasp, both of which have a significant role in coastal lemon IPM. Dimethoate and acephate greatly reduced populations of both beneficial insects, holding them to below detectable levels for 8 weeks post-treatment. Moreover, citrus red mite (Panonychus citri), a secondary pest, developed beyond the economic treatment threshold in both the dimethoate and acephate plots 10 weeks and 4 weeks post-treatment,

respectively. In addition to predatory mite mortality, hormoligosis is suspected in both instances, and especially with acephate, of causing this secondary pest problem.[Phillips PA et al; Crop Prot 6 (6): 38892 (1987)] **PEER REVIEWED** /FIELD STUDIES/ Acephate was added to a small, coastal B. C. stream to yield a concentration of 1100-1200 ppb for a 5-hr period. It was rapidly taken up by fish, sediments, insect nymphs and larvae. No fish or insect mortality was noted although the more toxic methamidophos was found in both groups of animals. Acephate and methamidophos residues in animals and sediments declined to trace or non-detectable levels in 24 hr and to these levels in water by 96 hr. The impact of acephate on the stream and its fauna was limited and localized.[Geen GH et al; J Environ Sci Health B 16 (3): 253-71 (1981)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7252062" target=new>PubMed Abstract /FIELD STUDIES/Acephate and its degradate methamidophos are highly toxic to honey bees and beneficial predatory insects on an acute contact basis. Acute and chronic risks to birds and chronic risk to mammals are also high. 2[EPA/Office of Prevention, Pesticides, and Toxic Substances; Fact Sheet for Acephate. 4 p (EPA 738-F-01-013) (September 2001)] **PEER REVIEWED** /FIELD STUDIES/ Aerial spraying of acephate (0.6 kg/hectare) resulted in a decline in numbers of red eyed vireos; however, significant decreases in numbers of other passerines were not observed. No mortality was documented during this study.[Smith GJ; Pesticide Use and Toxicology in Relation to Wildlife: Organophosphorus and Carbamate Compounds p.12 (1987)] **PEER REVIEWED** /FIELD STUDIES/ Aerial spray at rate of 0.6 kg/hectare resulted in no forest significant effects on numbers, survival, and reproduction of

birds. Aerial spraying at 1.1 kg/hectare (1 lb/acre) resulted in possible sickness and death of some forest birds in one study. One aerial application of 0.6 kg/hectare produced cholinesterase inhibition in songbirds and squirrels; however, no mortality was observed. Songbird cholinesterase activity was significantly inhibited in 19 of 19, 45 of 84, 15 of 58, and 16 of 62 songbirds analyzed from an area treated aerially at 2.2, 1.1, 1.1, and 0.6 kg/hectare, respectively.[Smith GJ; Pesticide Use and Toxicology in Relation to Wildlife: Organophosphorus and Carbamate Compounds p.12 (1987)] **PEER REVIEWED** NON-HUMAN TOXICITY VALUES: LD50 Rat male oral 945 mg/kg /Technical grade/[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 1] **PEER REVIEWED** LD50 Rat female oral 866 mg/kg /Technical grade/[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 1] **PEER REVIEWED** LD50 Rat, male acute oral (technical) 866 mg/kg[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4809] **PEER REVIEWED** LD50 Rat, female acute oral (technical) 945 mg/kg[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4809] **PEER REVIEWED** E. LD50 Mouse acute oral (technical) 361 mg/kg[Clayton, G. D. and F.

Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4809] **PEER REVIEWED**

LD50 Rabbit acute dermal greater than 2000 mg/kg body weight[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4810] **PEER REVIEWED** LD50 Rabbit, male acute dermal > 10,000 mg/kg[Purdue University; National Pesticide Information Retrieval System, Acephate Fact Sheet No. 140 (1987)] **PEER REVIEWED** LD50 Dog oral > 681 mg kg/kg bw[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 95] **PEER REVIEWED** LD50 Mouse oral 233 mg/kg[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley &amp; Sons, Inc. Hoboken, NJ. 2004., p. 1372] **PEER REVIEWED** ECOTOXICITY VALUES: EC50 Daphnia magna /(water flea)/ 309.82 uM/48 hrs; immobility. [Printes LB, Callaghan A; Environ Toxicol Chem 23 (5): 1241-7 (2004)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15180375" target=new>PubMed Abstract LC50 Gammarus pseudolimnaeus > 50 ug/l/96 hr at 12 deg C, mature. Static bioassay without aeration, pH 7.2-7.5, water hardness 4050 mg/l as calcium carbonate and alkalinity of 30-35 mg/l. Technical material, 94%.[U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 8] **PEER REVIEWED** LC50 /Oncorhynchus mykiss/ (Rainbow trout, weight 1.5 g) 1,100 ug/L/96 hr at 10 deg C. Static bioassay without aeration, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L. Technical material, 94%.[U.S. Department of Interior, Fish and Wildlife Service.

Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 8] **PEER REVIEWED** LC50; Species: Oncorhynchus mykiss (Rainbow trout); Conditions: freshwater; static; Concentration: 880 ppm for 24 hr /technical product/[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Oncorhynchus mykiss (Rainbow trout weight 1.5 g); Conditions: freshwater; static; Concentration: 730 ppm for 96 hr /75 WP formulated product/[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50 Pimephales promelas (Fathead minnow, weight 1.0 g) > 1000 ug/L/96 hr at 20 deg C. Static bioassay without aeration, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L. Technical material, 94%.[U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 9] **PEER REVIEWED** LC50; Species: Pimephales promelas (Fathead minnow); Conditions: freshwater; static, 22 deg C pH 7.4, hardness 40 mg/L CaCO3; Concentration: > 50 mg/L for 96 hr /94% technical product/ [Sanders HO et al; Tech Pap No.110, US Fish Wildl Serv, Washington DC: 1-5 (1983). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50 Lepomis machrochirus (Bluegill, weight 0.4 g) > 1000 ug/L/96 hr at 20 deg C. Static bioassay without aeration, pH 7.2-7.5, water hardness 40-50 mg/L as calcium carbonate and alkalinity of 30-35 mg/L. Technical material, 94%.[U.S. Department of Interior, Fish and Wildlife Service. Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates.

Resource Publication No. 137. Washington, DC: U.S. Government Printing Office, 1980., p. 9] **PEER REVIEWED** LC50; Species: Lepomis macrochirus (Bluegill, weight 0.4 g); Conditions: freshwater; static, 20 deg C, pH 7.4, hardness 40 mg/L CaCO3; Concentration: 200 mg/L for 24 hr /75% pure/[Mayer FL Jr, Ellersieck MR; Resour Publ No.160, US Dep Interior, Fish Wildl Serv, Washington DC: 505 (USGS Data File) (1986). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Lepomis macrochirus (Bluegill, weight 0.4 g); Conditions: freshwater; static, 12 deg C, pH 7.4, hardness 44 mg/L CaCO3; Concentration: > 50 mg/L for 24 hr /94% pure technical material/[Mayer FL Jr, Ellersieck MR; Resour Publ No.160, US Dep Interior, Fish Wildl Serv, Washington DC: 505 (USGS Data File) (1986). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Lepomis macrochirus (Bluegill, weight 0.8 g); Conditions: freshwater; static, 17 deg C, pH 6.5, hardness 40 mg/L CaCO3; Concentration: > 50 mg/L for 24 hr /94% pure technical material/[Mayer FL Jr, Ellersieck MR; Resour Publ No.160, US Dep Interior, Fish Wildl Serv, Washington DC: 505 (USGS Data File) (1986). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Lepomis macrochirus (Bluegill, weight 0.6 g); Conditions: freshwater; static, 17 deg C, pH 7.4, hardness 40 mg/L CaCO3; Concentration: > 50 mg/L for 24 hr /94% pure technical material/[Mayer FL Jr, Ellersieck MR; Resour Publ No.160, US Dep Interior, Fish Wildl Serv, Washington DC: 505 (USGS Data File) (1986). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Lepomis macrochirus (Bluegill, weight 0.6 g); Conditions: freshwater; static, 17 deg C, pH 7.4, hardness 320 mg/L CaCO3;

Concentration: > 50 mg/L for 24 hr /94% pure technical material/[Mayer FL Jr, Ellersieck MR; Resour Publ No.160, US Dep Interior, Fish Wildl Serv, Washington DC: 505 (USGS Data File) (1986). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50 Coturnix 3,275 ppm/5 days (95% confidence interval: 2691-3986 ppm)[Hill, E.F. and Camardese, M.B. Lethal Dietary Toxicities of Environmental Contaminants and Pesticides to Coturnix. Fish and Wildlife Technical Report 2. Washington, DC: United States Department of Interior Fish and Wildlife Service, 1986., p. 21] **PEER REVIEWED** ppm/14 LC50; Species: Anas platyrhynchos (Mallard duck) diet > 5000

days[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December 21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LD50; Species: Anas platyrhynchos (Mallard duck) oral 350 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December 21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LD50; Species: Anas platyrhynchos (Mallard duck, 4-6 months) oral 234 mg/kg (95% confidence interval: 186-295 mg/kg)[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December 21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** 20,000 LC50; Species: Colinus virginianus (Northern bobwhite) diet >

ppm/10 days[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December 21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LD50; Species: Colinus virginianus (Northern bobwhite, age 9 months) oral > 2510 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December

21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LD50; Species: Phasianus colchicus (Ring-necked pheasant) oral 140 mg/kg (95% confidence interval: 105-187 mg/kg)[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of December 21, 2006: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Gambusia affinis (Mosquitofish); Conditions: freshwater; static; Concentration: 16.37 ppm for 96 hr (95% confidence interval: 13.7-19.1 ppm) /77.1% AI formulated product/[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50; Species: Micropterus salmoides (Largemouth bass, weight 11.3 g); Conditions: freshwater; static; Concentration: 3000 ppm for 96 hr /75% AI formulated product/[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on Acephate (30560-19-1). Available from, as of January 18, 2007: http://cfpub.epa.gov/ecotox/quick_query.htm] **PEER REVIEWED** LC50 Largemouth black bass 1725 mg/L for 96 hr /conditions of bioassay not specified/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 95] **PEER REVIEWED** LC50 Ictalurus punctatus (channel cat fish) 2230 mg/L for 96 hr /conditions of bioassay not specified/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 95] **PEER REVIEWED** LC50 Penaeus duorarum (pink shrimp) 3.8 mg/L for 96 hr /conditions of bioassay not specified/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 95] **PEER REVIEWED** LC50 Mysid shrimp 7.3 mg/L for 96 hr /conditions of bioassay not

specified/[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley &amp; Sons. New York, NY. 2001, p. 95] **PEER REVIEWED** METABOLISM/PHARMACOKINETICS: METABOLISM/METABOLITES: ... Acephate treated /White Leghorn laying hen/ received appropriate doses, 5 to 700 mg/kg, of the agent dissolved in water by gavage at 5 ml/kg. The birds were sacrificed 23.5 to 24 hr after treatment. Brain methamidophos levels were 10 to 16% of the total acephate plus methamidophos brain concentration. The lower the dose of acephate, the higher the relative percentage of methamidophos.[Wilson BW et al; Neurotoxicology 11 (3): 483-491 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2284053" target=new>PubMed Abstract In plant tissue, orthene is partially metabolized to O,S-dimethyl phosphoramidothioate, the active ingredient in the insecticide monitor. /Monitor - product name/[Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 193] **PEER REVIEWED** Toxicity of orthene to insects was related to monitor production and degradation. O- and S-Demethylation, prior to deacetylation, contributed to resistance. With excised cotton leaves, orthene was converted to some monitor as well as O-demethyl orthene. /Monitor - product name/ [Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific ReportWildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980., p. 406] **PEER REVIEWED** Plasma &amp; tissue enzymes are responsible for hydrolysis /of organophosphorus compounds/ to the corresponding phosphoric &amp; phosphonic acids. However, oxidative enzymes are also involved in the metabolism of some organophosphorus compounds. /Organophosphorus

compounds/[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 139] **PEER REVIEWED** These chemicals are detoxified by cytochrome p450-mediated monooxygenases in the liver, but some metabolites are more toxic than parent cmpd ... Metabolites usually are detected from 12 to 48 hr postexposure. /Organophosphate cmpd/[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1071] **PEER REVIEWED** ABSORPTION, DISTRIBUTION & EXCRETION: Within 1 hr, 130 day-old loblolly pine seedlings absorbed and distributed (14)C-orthene from nutrient solution.[Menzie, C.M. Metabolism of Pesticides, Update II. U.S. Department of the Interior, Fish Wildlife Service, Special Scientific Report - Wildlife No. 2l2. Washington, DC: U.S. Government Printing Office, 1978., p. 193] **PEER REVIEWED** Most organophosphate compounds are ... absorbed from skin, conjunctiva, gastrointestinal tract, &amp; lung. /Organophosphate compounds/ [Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1071] **PEER REVIEWED** The rate of dermal absorption /of organophosphorus pesticides/ may be ... influenced by the solvent used. /Organophosphorus pesticides/ [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 147] **PEER REVIEWED** ... The organophosphorus insecticides are, in contrast to the chlorinated insecticides, rapidly metabolized &amp; excreted and are not appreciably stored in body tissues. /Organophosphorus insecticides/[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 832] **PEER REVIEWED** Many of the organophosphorus insecticides are excreted in the milk. ...

D. J.

/Organophosphorus insecticides/[Clarke, M. L., D. G. Harvey and

Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 148] **PEER REVIEWED** An investigation was conducted of inhalation and skin acephate exposures in pesticide formulation workers. The cohort consisted of four persons employed at a small Italian pesticide formulation factory. Breathing zone samples were collected over a full 8 hour shift and analyzed for acephate. Gauze pads were attached to the hands, face, and body of two workers to measure skin exposure. Urine samples were collected daily and analyzed for acephate and methamidophos, a major acephate metabolite. Venous blood samples were collected and analyzed for erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (PChE). Median 8 hour time weighted acephate concentrations ranged from 0.278 to 2.170 mg/m3. Urine acephate concentrations ranged from 1 to 10 milligrams per liter (mg/L), median 0.4 to 1.1mg/L. Methamidophos was not detected in any samples. Median total skin deposition of acephate ranged from 26.1 to 41.9 milligrams per day (mg/day). Assuming that 30 to 50% of the breathing zone exposure and 10 to 20% of the skin dose were absorbed, the median intake of acephate was estimated to be 10 to 20 mg/day. Skin absorption was significantly correlated with urinary excretion of acephate. No significant changes in AChE or PChE activity were noted in subjects whose urinary acephate concentrations averaged 1 to 2mg/L or less. Higher urinary acephate concentrations were associated with a 20% decrease in PChE and an 18% decrease in AChE activity. These decreases were not considered biologically significant. The authors conclude that this investigation does not support the notion that acephate is substantially converted into methamidophos in humans. NOTE: Methamidophos may be RELT[Maroni M et al; Arch Environ Contam Toxicol 19 (5): 782-8 (1990)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2241237" target=new>PubMed Abstract

... Male Wistar rats ... received by stomach tube a single 270 milligram per kilogram dose of acephate. Blood samples were obtained at 0.5, 8, 24, and 72 hours after dosing and were analyzed for erythrocyte and plasma cholinesterase activity. Rats were then sacrificed and the brains and livers were excised. Brains were homogenized, centrifuged, and the supernatants were analyzed for cholinesterase activity. Livers were cut into small pieces, added to acetonitrile and analyzed for acephate. Acephate was found to be quickly absorbed from the intestines and transported to the liver. This rapid increase was followed by a decline until by the end of 72 hours little or no acephate was found in the liver. Erythrocyte and brain cholinesterases were inhibited by nearly 50 percent and plasma cholinesterase by 18 percent at 0.5 hour after dosing. A recovery then occurred so that after 72 hours enzyme activities were about 85 percent of normal. The authors conclude that, compared to paraoxon, acephate is approximately six orders of magnitude weaker as an inhibitor of cholinesterases.[Hussain MA et al; J Environ Sci and Health B20 (1): 129047 (1985)] **PEER REVIEWED** MECHANISM OF ACTION: Many of the more recently introduced organophosphorus esters (acephate ...) are less tenacious inhibitors of nervous tissue acetylcholinesterase, the phosphorylated enzyme being more readily and spontaneously dissociated.[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991., p. 585] **PEER REVIEWED** Organophosphorus derivatives act by combining with and inactivating the enzyme acetylcholinesterase. ... The inactivation of cholinesterase by cholinesterase inhibitor pesticides allows the accumulation of large amounts of acetylcholine, with resultant widespread effects that may be ... separated into 4 categories: (1) Potentiation of postganglionic parasympathetic activity. ... (2) Persistent depolarization of skeletal

of

muscle ... (3) Initial stimulation following depression of cells

central nervous system ... (4) Variable ganglionic stimulation or blockade ... /Cholinesterase inhibitor pesticides/[Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987., p. 113] **PEER REVIEWED** 1. The molecular composition of acetylcholinesterase (acetylcholinesterase) obtained from cockroach neural, and rat brain tissues was different. Vertebrate enzyme exhibited a higher degree of polymerization than insect enzyme. 2. Acephate was a potent inhibitor of cockroach acetylcholinesterase, but a poor inhibitor of rat acetylcholinesterase. Unlike acephate, methamidophos was a potent inhibitor of both cockroach and rat enzymes. Acephate exhibited greater affinity for the cockroach acetylcholinesterase than for the rat acetylcholinesterase, and acephate phosphorylated the cockroach acetylcholinesterase several times faster than the rat enzyme. The rate of phosphorylation of insect and rat acetylcholinesterase was similar in the presence of methamidophos. Solubilization of acetylcholinesterase by Triton X-100 altered the kinetics of inhibition of rat acetylcholinesterase by acephate. However, solubilization did not alter the kinetics of inhibition of rat acetylcholinesterase by methamidophos or the kinetics of inhibition of cockroach acetylcholinesterase by acephate or methamidophos. 3. The mechanism of acephate cockroach acetylcholinesterase interaction was different than the mechanism of acephate rat acetylcholinesterase interaction. It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an "electron deficient" binding site which may exhibit selectivity for acephate and nefopam. The electron deficient site in rat acetylcholinesterase has allosteric properties, whereas the cockroach acetylcholinesterase does not. It is also proposed that the electron deficient site in cockroach acetylcholinesterase may be situated in or adjacent to the active site and, therefore, acephate may be bound to the electron deficient site such that the phosphate moiety of acephate

interacts with the enzyme's "esteratic" site. Although nefopam also bound to the electron deficient site in cockroach acetylcholinesterase, it did not inhibit the enzyme. This study also indicated that the electron deficient site in rat acetylcholinesterase may be peripheral to the active site, and that the binding of acephate to this site prevented the phosphorylation by methamidophos of the rat acetylcholinesterase. Unlike acephate, methamidophos specifically bound to the active site in both the rat and cockroach acetylcholinesterase.[Singh AK; Toxicol Ind Health 6 (6): 551-70 (1990)] **PEER REVIEWED** INTERACTIONS: Anticholinesterase (organophosphorus) insecticides antagonize polarizing muscle relaxants. Phenothiazines /and thioxanthene/: ...may enhance toxic effects of organophosphorus insecticides. /Insecticides, organophosphorus/[Martin E. Hazards of Medication: A Manual on Drug Interactions, Incompatibilities, Contraindications and Adverse Effects. Philadelphia: J.B. Lippincott Co., 1971., p. 637] **PEER REVIEWED** ... Aluminium, a common metal compound, and acephate, an organophosphorous pesticide, are two widely used chemicals known for their neurotoxic effects. To assess the toxic interaction of aluminium and acephate, acute toxicity study of aluminium chloride, acephate, and their combination was made. Male Wistar albino rats were dosed orally in a increasing geometric progressive doses of aluminium chloride, acephate, and their combination (1 part aluminium:1 part acephate) in distilled water. The median lethal oral dose of aluminium chloride, acephate, and their combination was found to be 3630 +/- 400, 2851 +/- 269, and 4074 +/- 388 mg/kg body weight respectively. Log dose-response curve revealed the acute toxic effects of combination of metal and pesticide to be reduced, suggesting antagonistic action. Antagonistic action of the combination of compounds shows that aluminium reduced the toxic effect of organophosphorous pesticide acephate. ...[Kumar S; Int J Toxicol 20 (4): 219-23 (2001)] **PEER REVIEWED** <a

href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11563417" target=new>PubMed Abstract The efficacy of a reactive skin decontaminant lotion against organophosphorus nerve agents in-vivo was examined. The agents used included tabun, sarin, soman, and VX. The decontaminant location consisted of a 1.25 modal solution of the potassium salt of 2,3-butanedione monoxime in polyethylene glycol methylether and 10% water mixture. This reactive skin decontaminant was highly effective against each of the four agents tested. In Sprague Dawley rats the inactivation process was dose dependent, with a 1:1 organophosphorus/potassium salt of 2,3-butanedione-monoxime molar ratio offering total protection against the toxic effects. The inactivation process, as a function of anticholinesterase activity in primary cultures of chick embryo neurons, was also time, dose and agent dependent. Soman was relatively slow in detoxifying over a 24 hour period when compared to the other three agents. Even so, in all cases less than 0.1% of the original organophosphate anticholinesterase activity remained after a 7 day period. It was concluded that this cell culture system is advantageous in evaluating the prophylaxis and therapy of nerve agent poisoning.[Sawyer TW et al; Toxicol 67 (3): 267-7 (1991)] **PEER REVIEWED** PHARMACOLOGY: INTERACTIONS: Anticholinesterase (organophosphorus) insecticides antagonize polarizing muscle relaxants. Phenothiazines /and thioxanthene/: ...may enhance toxic effects of organophosphorus insecticides. /Insecticides, organophosphorus/[Martin E. Hazards of Medication: A Manual on Drug Interactions, Incompatibilities, Contraindications and Adverse Effects. Philadelphia: J.B. Lippincott Co., 1971., p. 637] **PEER REVIEWED** ... Aluminium, a common metal compound, and acephate, an organophosphorous pesticide, are two widely used chemicals known for their neurotoxic

effects. To assess the toxic interaction of aluminium and acephate, acute toxicity study of aluminium chloride, acephate, and their combination was made. Male Wistar albino rats were dosed orally in a increasing geometric progressive doses of aluminium chloride, acephate, and their combination (1 part aluminium:1 part acephate) in distilled water. The median lethal oral dose of aluminium chloride, acephate, and their combination was found to be 3630 +/- 400, 2851 +/- 269, and 4074 +/- 388 mg/kg body weight respectively. Log dose-response curve revealed the acute toxic effects of combination of metal and pesticide to be reduced, suggesting antagonistic action. Antagonistic action of the combination of compounds shows that aluminium reduced the toxic effect of organophosphorous pesticide acephate. ...[Kumar S; Int J Toxicol 20 (4): 219-23 (2001)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11563417" target=new>PubMed Abstract The efficacy of a reactive skin decontaminant lotion against organophosphorus nerve agents in-vivo was examined. The agents

used

included tabun, sarin, soman, and VX. The decontaminant location consisted of a 1.25 modal solution of the potassium salt of 2,3-butanedione monoxime in polyethylene glycol methylether and 10% water mixture. This reactive skin decontaminant was highly effective against each of the four agents tested. In Sprague Dawley rats the inactivation process was dose dependent, with a 1:1 organophosphorus/potassium salt of 2,3-butanedione-monoxime molar ratio offering total protection against the toxic effects. The inactivation process, as a function of anticholinesterase activity in primary cultures of chick embryo neurons, was also time, dose and agent dependent. Soman was relatively slow in detoxifying over a 24 hour period when compared to the other three agents. Even so, in all cases less than 0.1% of the original organophosphate anticholinesterase activity remained after a 7 day period. It was concluded that this cell culture system is advantageous in evaluating the prophylaxis and therapy of nerve agent poisoning.[Sawyer TW et al; Toxicol 67 (3): 267-7 (1991)] **PEER REVIEWED**

ENVIRONMENTAL FATE & EXPOSURE: ENVIRONMENTAL FATE/EXPOSURE SUMMARY: Acephate's production may result in its release to the environment through various waste streams; its use as an insecticide will result in its direct release to the environment. If released to air, a vapor pressure of 1.7X10-6 mm Hg at 25 deg C indicates that acephate is expected to exist in both the vapor and particulate-phases in the ambient atmosphere. Vapor-phase acephate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 34 hours. Particulate-phase acephate will be removed from the atmosphere by wet or dry deposition. Acephate was photolytically stable in aqueous solutions exposed to natural sunlight, suggesting photolysis will not be an important fate process. If released to soil, acephate is expected to have very high mobility based upon a Koc value of 4.7 measured in a clay loam. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5X10-13 atm-cu m/mole. Volatilization from dry soil is not expected based upon the vapor pressure. Acephate is non-persistent in the environment with observed half-lives of < 3 days in laboratory studies and terrestrial field dissipation studies. If released into water, acephate is not expected to adsorb to suspended solids and sediment based upon the Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. Acephate was stable to hydrolysis at pH 5 and 7, but degraded with a half-life of 18 days at pH 9. A BCF value of 10 measured in fish suggests that bioconcentration in aquatic organisms is low. Occupational exposure to acephate may occur through inhalation of dust and dermal contact with this compound at workplaces where acephate is

produced or used. Monitoring data indicate that the general population may be exposed to acephate via ingestion of food containing acephate. (SRC) **PEER REVIEWED** PROBABLE ROUTES OF HUMAN EXPOSURE: NIOSH (NOES Survey 1981-1983) has statistically estimated that 770 (378 of these are female) workers are potentially exposed to acephate in the USA(1). The NOES Survey does not include farm workers; therefore, the actual number of exposures may be underestimated. Occupational exposure to acephate may occur through inhalation of dust and dermal contact with this compound at workplaces where acephate is produced or used(SRC). Four workers involved in the formulation of acephate products were monitored over an 8 day period to determine inhalation and dermal exposures(2); median air concns (8 hr TWA) ranged from 0.278 to 2.17 mg/cu m and median total-body skin deposition ranged from 26.1 to 41.9 mg/day(2). Monitoring data indicate that the general population may be exposed to acephate via ingestion of food(SRC).[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983). Available at http://www.cdc.gov/noes/noes1/t0473sic.html as of Jan 12, 2007. (2) Maroni M et al; Arch Environ Contam Toxicol 19: 782-8 (1990)] **PEER REVIEWED** AVERAGE DAILY INTAKE: FOOD: The FDA's Total Diet Study for 1988 reported the following average daily intakes (in ug/kg body wt/day) for acephate(1): infants (611 mo old) - 0.0105, 14-16 yr old males-0.0080, 60-65 yr old females0.0104(1). The FDA's Total Diet Study for 1982-1984 reported the following average daily intakes (in ug/kg body wt/day) for acephate(1): infants (611 mo old) - 0.0003, toddlers (2 yr old): 0.0011, 14-16 yr old females: 0.0008, 14-16 yr old males-0.0016, 25-30 yr-old females-0.0025, 25-30 yr old males-0.0026, 60-65 yr old females-0.0022, 60-65 yr old males-0.0017(2).[(1) FDA; Food &amp; Drug Administration Pesticide Program: Residues in Foods-1988, Washington DC: FDA (1989) (2) Gunderson EL; J Assoc Off Anal Chem 71: 1200-9 (1988)] **PEER REVIEWED**

ARTIFICIAL POLLUTION SOURCES: Acephate's production may result in its release to the environment through various waste streams; its use as an insecticide(1) will result in its direct release to the environment(SRC).[(1) USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R01-013, September 2001. Available at: http://www.epa.gov/pesticides/reregistration/status.htm as of Jan 12, 2007.] **PEER REVIEWED** ENVIRONMENTAL FATE: TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 4.7 measured in a clay loam(2), indicates that acephate is expected to have very high mobility in soil(SRC). Volatilization of acephate from moist soil surfaces is not expected(SRC) based upon an estimated Henry's Law constant of 5X10-13 atm-cu m/mole(SRC), derived from its vapor pressure, 1.7X10-6 Hg mm(3), and water solubility of 8.18X10+5 mg/L(3). Acephate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Acephate degraded in aerobic soils and terrestrial field dissipation studies with half-lives of < 3 days(4).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R-01-013, September 2001. Available at: http://www.epa.gov/pesticides/reregistration/status.htm as of Jan 12, 2007. (3) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-35 (1991) (4) USEPA; Organophosphate Pesticide Tolerance Reassessment and Reregistration. Acephate. Revised Environmental Fate and Effects Assessment. EFED Acephate Environmental Fate RED Chapter. Washington, DC: USPEA. Available at : http://www.epa.gov/oppsrrd1/op/acephate/efedrra.pdf as of Jan 12, 2007.] **PEER REVIEWED** AQUATIC FATE: Based on a classification scheme(1), a Koc value of 4.7 measured in a clay loam(2), indicates that acephate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water

surfaces is not expected(3) based upon an estimated Henry's Law constant of 5X10-13 atm-cu m/mole(SRC), derived from its vapor pressure, 1.7X10-6 Hg mm(4), and water solubility of 8.18X10+5 mg/L(4). According to a classification scheme(5),a BCF of 10 measured in fish(2), suggests bioconcentration in aquatic organisms is low(SRC). Acephate was stable to hydrolysis in pH 5 and 7 aqueous buffered solutions, but degraded with a half-life of 18 days at pH 9(5). Acephate degraded 54.8% in a river die-away test using creek water over a 50-day incubation period(5). Acephate degraded with a half-life of 6.6 days in a flooded clay sediment maintained under anaerobic conditions(6).[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R-01-013, September 2001. Available at: http://www.epa.gov/pesticides/reregistration/status.htm as of Jan 12, 2007. (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-35 (1991) (5) Franke C et al; Chemosphere 29: 1501-14 (1994) (5) Szeto SY et al; J Environ Sci Health B14: 635-54 (1979) (6) USEPA; Organophosphate Pesticide Tolerance Reassessment and Reregistration. Acephate. Revised Environmental Fate and Effects Assessment. EFED Acephate Environmental Fate RED Chapter. Washington, DC: USPEA. Available at : http://www.epa.gov/oppsrrd1/op/acephate/efedrra.pdf as of Jan 12, 2007.] **PEER REVIEWED** ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acephate which has a vapor pressure of 1.7X10-6 mm Hg at 25 deg C(2), is expected to exist in both the vapor and particulate-phases in the ambient atmosphere(SRC). Vapor-phase acephate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 34 hours(SRC), calculated from its rate

was

constant of 1.1X10-11 cu cm/molecule-sec at 25 deg C(SRC), that

derived using a structure estimation method(3). Particulate-phase acephate will be removed from the atmosphere by wet or dry deposition(SRC). Acephate was photolytically stable in aqueous solutions exposed to natural sunlight(4), suggesting photolysis in air will not be an important fate process(SRC).[(1) Bidleman TF; Environ Sci Technol 22: 361-7 (1988) (2) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-35 (1991) (3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (4) USEPA; Organophosphate Pesticide Tolerance Reassessment and Reregistration. Acephate. Revised Environmental Fate and Effects Assessment. EFED Acephate Environmental Fate RED Chapter. Washington, DC: USPEA. Available at : http://www.epa.gov/oppsrrd1/op/acephate/efedrra.pdf as of Jan 12, 2007.] **PEER REVIEWED** ENVIRONMENTAL BIODEGRADATION: AEROBIC: River die-away studies determined that acephate degraded more rapidly in non-sterile creek water as compared to sterilized creek water(1); after 50 days of incubation, 54.8% of initial acephate was degraded in non-sterile water while only 23.6% had degraded in sterile water(1); in water plus sediment tests, 74.5% degraded in nonsterile media while only 45% degraded in sterile media(1). Acephate degraded in aerobic soils with half-lives of generally < 3 days(2). Acephate, applied at concentrations of 1 or 10 ppm was rapidly degraded from a wide variety of soils (eight soils - 3 clays, loam, loamy sand, sandy clay loam, silty clay loam, muck) when incubated at 24 deg C at field capacity open to the air (volatiles not trapped and degradates other than methamidophos were not identified). In all cases, half-lives in mineral soils were < 3 days at 10 ppm and about 1.5 days at 1 ppm(2). Half-lives in an Ocoee muck soil (pH 5.3, 68% organic matter) were 6 days at 1 ppm and 13 days at 10 ppm(2). Average maximum concentrations of methamidophos were approximately 10% of the initially applied radioactivity. In sterile controls (Norwalk silty clay loam and Greenville clay), after 4 days,

approximately 90-100% of the applied amount remained as acephate, compared to approximately 20 % in the non-sterile(2). The effect of varying moisture contents (5 and 15%) was tested with the Hanford loamy sand treated with 20 ppm acephate; volatiles were not trapped. Degradation was more rapid at 15% moisture content than at 5%(2). Acephate degraded with a first-order half-life of 6.6 days in anaerobic flooded clay sediment(2). The initial pH of the system was 7.0, increasing to pH 7.9 by the final sampling interval (day 20). Acephate, applied as a wettable powder at 0.75 lbs/A, dissipated with an observed half-life of 1-3 days in the upper 5 cm of a field plot of silt loam soil used for growing tobacco in Greenville, Mississippi, after six foliar applications (6- to 9-day intervals)(2).[(1) Szeto SY et al; J Environ Sci Health B14: 635-54 (1979) (2) USEPA; Organophosphate Pesticide Tolerance Reassessment and Reregistration. Acephate. Revised Environmental Fate and Effects Assessment. EFED Acephate Environmental Fate RED Chapter. Washington, DC: USPEA. Available at : http://www.epa.gov/oppsrrd1/op/acephate/efedrra.pdf as of Jan 12, 2007.] **PEER REVIEWED** ENVIRONMENTAL ABIOTIC DEGRADATION: The rate constant for the vapor-phase reaction of acephate with photochemically-produced hydroxyl radicals has been estimated as 1.1 X10-11 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 34 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1) Hydrolysis of acephate at 20 deg C was measured in buffered distilled water over a 20 day period(1); the percentage of initial acephate that hydrolyzed ranged from 2.4% at pH 4.0 to 22.1% at pH 8.2 with the hydrolysis rate increasing with increasing pH(2); at 30 deg C, the percentage of initial acephate that hydrolyzed ranged from 4.5% at pH 4.0 to 82.2% at pH 8.2(2). Hydrolysis tests conducted at 37 deg C identified DMPT (O,S-dimethyl phosphorothiolate) as the major hydrolysis product(3); methamidophos and OMPT (O-methylacetyl phosphoramidothiolate) were identified as minor hydrolysis products(3). The direct photolysis of

acephate was examined by exposing thin films of the compound to sunlight and ultraviolet light(4); no measurable photodegradation occurred in either sunlight or UV light after 72 hr exposures(4). Acephate, at 8.94 ppm, was photolytically stable in sterile pH 7 phosphate buffer solution that was irradiated for 35 days under natural sunlight(5). In sterile buffer in the presence of a photosensitizer (1% acetone), acephate, at 9.35 ppm, degraded with a dark-control-corrected half-life of 39.6 days in sterile pH 7 aqueous buffer solution that was irradiated for 31 days under natural sunlight(5). Acephate was hydrolytically stable in pH 5 and 7 aqueous buffer solutions, but the hydrolytic half-life was 18 days at pH 9 with O,S-dimethyl phosphorothioate, methamidophos, and O-methyl N-acetylphosphoramidate observed as degradation products(5).[(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (2)Szeto SY et al; J Environ Sci Health B14: 635-54 (1979) (3) Chukwudebe AC et al; J Environ Sci Health B19: 501-22 (1984) (4) Chukwudebe A et al; J Agric Food Chem 37: 539-45 (1989) (5) USEPA; Organophosphate Pesticide Tolerance Reassessment and Reregistration. Acephate. Revised Environmental Fate and Effects Assessment. EFED Acephate Environmental Fate RED Chapter. Washington, DC: USPEA. Available at : http://www.epa.gov/oppsrrd1/op/acephate/efedrra.pdf as of Jan 12, 2007.] **PEER REVIEWED** ENVIRONMENTAL BIOCONCENTRATION: Acephate residues did not bioaccumulate in the edible tissues or viscera of bluegill sunfish continuously exposed to 0.007 or 0.7 ppm acephate for 35 days(1). The average bioconcentration factor in edible tissues during the study was 10. In a model ecosystem study, acephate did not bioaccumulate in any of the organisms in the ecosystem that included algae, clam, crab, daphnia, elodea, fish, mosquito and snail(2). According to a classification scheme(3), this BCF value suggests bioconcentration in aquatic organisms is low(SRC).[(1) USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R-01-013, September 2001.

Available at: http://www.epa.gov/pesticides/reregistration/status.htm as of Jan 12, 2007. (2) Sanborn JR; The Fate of Selected Pesticides in the Aquatic Environment. USEPA-660/3-74-025. Ecol Res Series (1974) (3) Franke C et al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED** SOIL ADSORPTION/MOBILITY: In batch equilibrium studies using four soils, acephate was not sufficiently adsorbed in 3 of the soils to permit determination of the adsorption coefficient(1). The Koc of acephate in the fourth soil, a clay loam with pH 5.8 and 3.3% organic matter was reported as 4.7(1). Based on a classification scheme(2), this Koc value indicates that acephate is expected to have very high mobility in soil(SRC).[(1) USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R01-013, September 2001. Available at: http://www.epa.gov/pesticides/reregistration/status.htm as of Jan 12, 2007. (2) Swann RL et al; Res Rev 85: 23 (1983)] **PEER REVIEWED** VOLATILIZATION FROM WATER/SOIL: The Henry's Law constant for acephate is estimated as 5X10-13 atm-cu m/mole(SRC) derived from its vapor pressure, 1.7X10-6 mm Hg(1), and water solubility, 8.18X10+5 mg/L(1). This Henry's Law constant indicates that acephate is expected to be essentially nonvolatile from moist soil and water surfaces(2). Acephate is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).[(1) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-35 (1991) (2) Lyman W et al; Handbook of Chemical Property Estimation Methods Washington, DC: Amer Chem Soc pp. 15-15 to 15-29 (1990)] **PEER REVIEWED** EFFLUENT CONCENTRATIONS: An acephate concn of 134 mg/L was detected in the rinsate effluent from washing (rinsing) an airplane tank used to hold the insecticide during spray application(1).[(1) Woodrow JE et al; Bull Environ Contam Toxicol 42: 22-9 (1989)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2924002"

target=new>PubMed Abstract ATMOSPHERIC CONCENTRATIONS: SOURCE DOMINATED: An acephate concn of 15 ng/cu m was detected in the ambient air of a commercial pesticide storage building that was used to store 43 different pesticides(1).[(1) Yeboah PO, Kilgore WW; Bull Environ Contam Toxicol 32: 629-34 (1984)] **PEER REVIEWED** <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6743850" target=new>PubMed Abstract FOOD SURVEY VALUES: In the FDA's Total Diet Study (also known as the Market Basket Study since foods are purchased from local grocery stores throughout the US) for 1988, acephate was positively detected in 33 of 1170 food items (concn not reported, but the average daily intake for three age groups was approximately 0.01 ug/kg body wt/day)(1). During a 5 yr study conducted during 1981-1986, the Los Angeles District Office of the FDA analyzed 19,851 samples of domestic and imported food for pesticide residues(2-3); acephate was detected in 705 samples at concns ranging from 0.05 to > 2.0 ppm (all but 18 samples had concn of 1.0 ppm or less)(23). Acephate was identified in 16 out of 1,039 food items analyzed for in the 2003 FDA Market Basket Survey at a concentration range of 0.0070.459 ppm(4). Acephate was identified in 16 out of 1,030 food items analyzed for in the 2002 FDA Market Basket Survey at a concentration range of 0.002-0.350 ppm(4). Acephate was identified in 24 out of 1,030 food items analyzed for in the 2001 FDA Market Basket Survey at a concentration range of 0.002-0.505 ppm(4). Acephate was identified, not quantified, in an unspecified number of food items in the year 2000 FDA Market Basket Survey(4).[(1) FDA; Food &amp; Drug Administration Pesticide Program: Residues in the Foods-1988, Washington DC: FDA (1989) (2) Luke MA et al; J Assoc Off Anal Chem 71: 415-20 (1988) (3) Hundley HK et al; J Assoc Off Anal Chem 71: 875-92 (1988) (4) FDA; FDA Pesticide Program. Residue Monitoring 1993-2003. Available at:

**PEER

http://www.cfsan.fda.gov/~dms/pesrpts.html as of Jan 12, 2007.] REVIEWED**

ENVIRONMENTAL STANDARDS & REGULATIONS: FIFRA REQUIREMENTS: Tolerances for related pesticide chemicals. ... Where tolerances are established for residues of O,S-dimethyl phosphoramidothioate, resulting from the use of acephate (O,S-dimethyl acetylphosphoramidothioate) and/or O,S-dimethylphosphoramidothioate on the same agricultural commodity, the total amount of O,S-dimethyl-phosphoramidothioate shall not yield more residue than that permitted by the higher of the two tolerances. [40 CFR 180.3(d)(8); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** Tolerances are established for combined residues of acephate (O,S-dimethyl acetylphosphoramidothioate) and its cholinesterase-inhibiting metabolite O,S-dimethylphosphura-midothioate in or on raw agricultural commodities as follows: Commodity Bean (succulent and dry form, of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) Brussels sprouts (of which no more than 0.5 ppm is O,S-dimethyl phosphoramidothioate) Cattle, fat Cattle, meat byproducts Cattle, meat Cauliflower (of which no more than 0.5 ppm is O,S-dimethyl phosphoramidothioate) Celery (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) Cotton, undelinted seed Cotton, hulls Cotton, meal Cranberry (of which no more than 0.1 ppm is O,S-dimethyl phosphoramidothioate) Egg Goat, fat Goat, meat byproducts Goat, meat Hog, fat Hog, meat byproducts Hog, meat Horse, fat Horse, meat byproducts Horse, meat Lettuce, head (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) Milk Mint hay (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) Peanut Pepper (of which no more

than 1 ppm is O,S-dimethyl phosphoramidothioate) Poultry, fat Poultry, meat byproducts Poultry, meat Sheep, fat Sheep, meat byproducts Sheep, meat Soybean, meal Soybean [40 CFR 180.108(a)(1); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** A food additive tolerance is established for the combined residues of acephate (O,S-dimethyl acetylphosphoramidothioate) and its cholinesterase-inhibiting metabolite, methamidophos as follows: (i) In or on all food items (other than those already covered by a higher tolerance as a result of use on growing crops) in food handling establishments. (ii) The acephate may be present as a residue from applications of acephate in food handling establishments, including food service, manufacturing and processing establishments, such as restaurants, cafeterias, supermarkets, bakeries, breweries, dairies, meat slaughtering and packing plants, and canneries ... .[40 CFR 180.108(a)(2); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** Tolerances with regional registration, as defined in 180.1(n), are established for the combined residues of acephate and its cholinesterase-inhibiting metabolite in or on the following raw agricultural commodities: Commodity Nut, macadamia [40 CFR 180.108(c); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** Pesticide chemicals that cause related pharmacological effects will be regarded as having an additive deleterious action ... Where residues from two or more chemicals in the same class are present in or on a raw agricultural commodity that tolerance for the total of such residues shall be the same as that for the chemical having the lowest numerical tolerance in this class ... Acephate (O,S-dimethyl acetylphosphoramidothioate) and its cholinesterase-inhibiting metabolite O,S-dimethyl phosphoramidothioate are members of the class of cholinesterase-inhibiting pesticides. [40 CFR

180.3; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** The Agency has determined that acephate products are eligible for reregistration provided that: (i) any current data gaps and additional data needs are addressed; (ii) the risk mitigation measures outlined in this document are adopted, and label amendments are made to reflect these measures; and (iii) the consideration of cumulative risk for the organophosphates supports a final reregistration eligibility decision. The Agency has also not fully considered risks associated with exposure to methamidophos, a degradate of acephate, resulting from acephate use. Methamidophos is a registered OP pesticide that is currently undergoing reregistration. Once the methamidophos IRED is complete, the Agency will determine whether the methamidophos exposure resulting from acephate use poses risk concerns.[USEPA/Office of Pesticide Programs; Interim Reregistration Eligibility Decision (IRED) for Acephate p.38 738R-01-013 (September 2001). Available from, as of February 27, 2007: http://www.epa.gov/pesticides/reregistration/status.htm] **PEER REVIEWED** As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and Under environmental effects and make decisions about their future use.

this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Acephate is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA, as amended in 1988. Case No: 0042; Pesticide type: Insecticide; Registration Standard Date: 09/01/88; Case Status: OPP is reviewing data from the pesticide's producers regarding its human

health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Acephate; Data Call-in (DCI) Date(s): 10/15/92, 03/01/944, 03/03/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review p.82 (Spring, 1998) EPA 738-R-98-002] **PEER REVIEWED** ACCEPTABLE DAILY INTAKES: FAO/WHO ADI: 0.03 mg/kg[FAO/WHO; Pesticide Residues in Food 1990. Evaluations Part 1 - Residues p.417 Plant Prod Protect Paper 103/1 (1990)] **PEER REVIEWED** OPP RfD= 0.004 mg/kg; EPA RfD= 0.004 mg/kg[USEPA/OPP; Health Effects Div RfD/ADI Tracking Report p.2 (8/26/91)] **PEER REVIEWED** STATE DRINKING WATER GUIDELINES: (AZ) ARIZONA 4 ug/l[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER REVIEWED** (FL) FLORIDA 7.5 ug/l[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93) To Present] **PEER REVIEWED** ALLOWABLE TOLERANCES: Tolerances for related pesticide chemicals. ... Where tolerances are established for residues of O,S-dimethyl phosphoramidothioate, resulting from the use of acephate (O,S-dimethyl acetylphosphoramidothioate) and/or O,S-dimethylphosphoramidothioate on the same agricultural commodity, the total amount of O,S-dimethyl-phosphoramidothioate shall not yield more residue than that permitted by the higher of the two tolerances. [40 CFR 180.3(d)(8); U.S. National Archives and Records Administration's

Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** Tolerances are established for combined residues of acephate (O,S-dimethyl acetylphosphoramidothioate) and its cholinesterase-inhibiting metabolite O,S-dimethylphosphura-midothioate in or on raw agricultural commodities as follows: Commodity Parts per million Bean (succulent and dry form, of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) 3 Brussels sprouts (of which no more than 0.5 ppm is O,S-dimethyl phosphoramidothioate) 3.0 Cattle, fat 0.1 Cattle, meat byproducts 0.1 Cattle, meat 0.1 Cauliflower (of which no more than 0.5 ppm is O,S-dimethyl phosphoramidothioate) 2.0 Celery (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) 10 Cotton, undelinted seed 2 Cotton, hulls 4 Cotton, meal 8 Cranberry (of which no more than 0.1 ppm is O,S-dimethyl phosphoramidothioate) 0.5 Egg 0.1 Goat, fat 0.1 Goat, meat byproducts 0.1 Goat, meat 0.1 Hog, fat 0.1 Hog, meat byproducts 0.1 Hog, meat 0.1 Horse, fat 0.1 Horse, meat byproducts 0.1 Horse, meat 0.1 Lettuce, head (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) 10 Milk 0.1 Mint hay (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) 15.0 Peanut 0.2 Pepper (of which no more than 1 ppm is O,S-dimethyl phosphoramidothioate) 4.0 Poultry, fat 0.1 Poultry, meat byproducts 0.1 Poultry, meat 0.1 Sheep, fat 0.1 Sheep, meat byproducts 0.1 Sheep, meat 0.1 Soybean, meal 4 Soybean 1 [40 CFR 180.108(a)(1); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** A food additive tolerance of 0.02 ppm is established for the combined residues of acephate (O,S-dimethyl acetylphosphoramidothioate) and its cholinesterase-inhibiting metabolite, methamidophos as follows: (i) In or on all food items (other than those already covered by a higher tolerance as a result of use on growing crops) in food handling establishments. (ii) The acephate may be present as a residue from applications of acephate in food handling establishments, including food service, manufacturing and processing establishments, such as restaurants,

cafeterias, supermarkets, bakeries, breweries, dairies, meat slaughtering and packing plants, and canneries ...[40 CFR 180.108(a)(2); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED** Tolerances with regional registration, as defined in 180.1(n), are established for the combined residues of acephate and its cholinesterase-inhibiting metabolite in or on the following raw agricultural commodities: Commodity Parts per million Nut, macadamia 0.05 [40 CFR 180.108(c); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of February 5, 2007: http://www.gpoaccess.gov/ecfr] **PEER REVIEWED**

PREVENTIVE MEASURES: ... NOTES TO PHYSICIAN: This material contains a cholinesterase inhibitor. Measurement of blood cholinesterase activity may be useful in monitoring exposure. If signs and/or symptoms of cholinesterase inhibition appear, atropine sulfate is antidotal. ... PROTOPAM is also antidotal and may be used in conjunction with atropine but should not be used alone. /Orthene Fire Ant Killer 1 (50% acephate)/[The Scotts Company; MSDS for Orthene Fire Ant Killer 1. 10 p. (February 21, 2001). Available from, as of February 22, 2007: http://www.ortho.com/index.cfm/event/media.detail/documentId/a270 c9a6c39f3713713f73edeaef2347] **PEER REVIEWED** In order to mitigate occupational risks, the following risk mitigation measures are necessary: Formulate all soluble powder formulations into water soluble bags, except for soluble powders sold for fire ant, harvester ant, or hopper box seed treatment uses. Limit the 1 pound active ingredient per acre (lb ai/A) cotton aerial application rate to cotton grown in California and Arizona; reduce the maximum aerial application rate for cotton to 0.75 ai/A for all other areas of the United States. Delete aerial application to turf. Require enclosed cockpits and mechanical flagging for all aerial applications. Reduce maximum sod farm

and golf course turf application rates (non-granular formulations) to 3 lb ai/A and 4 lb ai/A, respectively. Reduce maximum application rates for greenhouse floral and foliage plant crops, and outdoor floral and ground covers to 1 lb ai per 100 gallons water (not to exceed 0.75 lb ai/A for cut flowers and 1.0 lb ai/A for other ornamentals). Delete the application of acephate by low pressure handwand to treat trees, shrubs, and outdoor flora; for the control of wasps; and for perimeter treatment by PCOs. Delete the use of granular formulations to be applied by belly grinder, shaker can, or by hand to trees, shrubs, and 12" pots. Add personal protective equipment to end use product labels for workers who mix and load, and/or apply acephate.[EPA/Office of Prevention, Pesticides, and Toxic Substances; Fact Sheet for Acephate. 4 p (EPA 738-F-01-013) (September 2001)] **PEER REVIEWED** In order to mitigate residential postapplication risk, the following risk mitigation measures are necessary: Delete residential indoor uses. Delete all turfgrass uses (except golf course, sod farm, and spot or mound treatment for ant control). Establish a 3 day pre-harvest interval (PHI) for the harvesting of sod.[EPA/Office of Prevention, Pesticides, and Toxic Substances; Fact Sheet for Acephate. 4 p (EPA 738-F-01-013) (September 2001)] **PEER REVIEWED** Keep out of reach of children. Avoid contact with mouth, skin, and eyes.[Meister, R.T., Sine, C; Crop Protection Handbook Volume 93. Meister Media Worldwide, Willoughby, OH 2007, p. D-7] **PEER REVIEWED** In case of damage to, or leaking from containers of this material, contact the Pesticide Safety Team Network at (800) 4249300 (800) 424-9300 . /Organophosphorus pesticide, solid not otherwise specified, (cmpd &amp; prepn) (insecticide, other than agricultural, not elsewhere classified); Organophosphorus pesticide, liq, not otherwise specified (cmpd &amp; prepn) (agricultural insecticides, not elsewhere classified, liq), (insecticides, other than

agricultural, not otherwise classified), and (agricultural insecticides, not elsewhere classified, liq); Organophosphorus pesticide, solid, not otherwise specified (cmpd &amp; prepn) (insecticides, other than agricultural, not elsewhere classified); and (agricultural insecticides, not elsewhere classified, other than liq)/[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, D.C.: Assoc. of American Railroads, Hazardous Materials Systems (BOE), 1987., p. 512] **PEER REVIEWED** The protective clothing should be kept in separate places where it cannot be contaminated with toxic chemicals. It should be forbidden to keep this clothing in living quarters. Protective clothing must be washed ... each time when it is contaminated with pesticides. Before washing the clothing should be soaked for several hours in a calcium carbonate solution. /Organophosphorus pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1646] **PEER REVIEWED** In some situations where personnel may become accidently contaminated ... it is necessary to provide shower bath in addition to the usual washing facilities. Special arrangements for cleaning clothing &amp; overalls may be necessary ... /Pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1619] **PEER REVIEWED** Special aircraft should preferably be used for spraying or dusting toxic organophosphorus pesticides. ... aerial spraying or dusting gives rise to clouds which spread over larger surfaces than clouds produced by ground application. Aerial spraying should therefore be carried out on windless days only. Residential areas, water supply sources, etc must be avoided. ... When aircraft approaches, signalmen /guiding the aircraft/ should leave the windward side. ... The local population should be informed about the site &amp; time of aerial pesticide treatment. Access of unauthorized

be ... area.

persons &amp; especially children to the area to be treated must forbidden. Warning signs should be placed at the limits of the

Ground spraying must be carried out with compressed-air spraying equipment towed by tractors with closed cabs. /Organophosphorus pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1645] **PEER REVIEWED** Small packages of pesticides are preferable for individual application in order to limit the quantities to be weighed &amp; metered. A special vessel with long stirring rod for dilution &amp; suspension of the poison must be available in order to reduce manual handling to a minimum. The strict observance of hygiene rules--no smoking &amp; no food intake during work. Thorough washing with soap after work, changing protective clothing before going home--is of utmost importance. /Organophosphorus pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1645] **PEER REVIEWED** such a who SRP: Contaminated protective clothing should be segregated in manner so that there is no direct personal contact by personnel

handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning. /Organophosphorus pesticides/ **PEER REVIEWED** Wear the items of protective clothing the label requires: for example, non-absorbent gloves (not leather or fabric), rubber footwear (not canvas or leather), a hat, goggles, or a dust-mist filter. If no specific clothing is listed, gloves, long-sleeved shirts and long pants, and closed shoes are recommended. You can buy protective clothing and equipment at

hardware stores or building supply stores.[USEPA/Prevention, Pesticides, and Toxic Substances; Citizen's Guide to Pest Control and Pesticide Safety p.19 (September 1995) EPA 730-K-95-001] **PEER REVIEWED** day Outdoor Applications. Never apply pesticides outdoors on a windy

(winds higher than 10 mph). Position yourself so that a light breeze does not blow pesticide spray or dust into your face.[USEPA/Prevention, Pesticides, and Toxic Substances; Citizen's Guide to Pest Control and Pesticide Safety p.21 (September 1995) EPA 730-K-95-001] **PEER REVIEWED** If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to knock-down vapors. /Organophosphorus pesticides, liquid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Use water spray to knock-down vapors. /Organophosphorus pesticides, flammable, toxic/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** Avoid Personnel protection: Avoid breathing vapors. Keep upwind. ...

bodily contact with the material ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. /Organophosphorus pesticides, liquid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous

Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** Personnel protection: Keep upwind. ... Do not handle broken packages unless wearing appropriate personal protective equipment. /Organophosphorus pesticides, liquid, flammable, toxic/ [Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. /Organophosphorus pesticides, solid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 679] **PEER REVIEWED** Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind. ... Avoid bodily contact with the material. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. /Organophosphorus pesticides, solid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 679] **PEER REVIEWED** STABILITY/SHELF LIFE: Relatively stable[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 4809] **PEER REVIEWED** SHIPMENT METHODS AND REGULATIONS: No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance

... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./[49 CFR 171.2 (7/1/96)] **PEER REVIEWED** The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.[IATA. Dangerous Goods Regulations. 38th ed. Montreal, Canada and Geneva, Switzerland: International Air Transport Association, Dangerous Goods Board, January, 1997., p. 190] **PEER REVIEWED** The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.[IMDG; International Maritime Dangerous Goods Code; International Maritime Organization p.30971, 6193, 6194, 6195 (1988)] **PEER REVIEWED** STORAGE CONDITIONS: Rooms used for storage only should be soundly constructed &amp; fitted with secure locks. Floors should be kept clear &amp; pesticides clearly identified. If repacking is carried out in storage rooms, adequate light should be available; floors should be impervious &amp; sound ... . /Pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1617] **PEER REVIEWED** degree give a Pesticides containers must be provided with labels indicating the of toxicity of the product they contain. The labels must not only short description of how to use the prepn, but also state basis

precautions to be taken when applying it. /Organophosphorus pesticides/[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1645] **PEER REVIEWED** Pesticides of any degree of toxicity should be transported in containers which are clearly labelled, leak-proof, and not easily damaged. They should never be transported beside, or above any type of food, and all spillages should be immediately reported. /Pesticides/ [International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&amp;II. Geneva, Switzerland: International Labour Office, 1983., p. 1616] **PEER REVIEWED** Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water.[USEPA/Prevention, Pesticides, and Toxic Substances; Citizen's Guide to Pest Control and Pesticide Safety p.23 (September 1995) EPA 730-K-95-001] **PEER REVIEWED** CLEANUP METHODS: Environmental considerations- land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder, or commercial sorbents. /Organophosphorus pesticides, liquid and solid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED**

Environmental considerations- water spill: Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction hoses. /Organophosphorus pesticides, liquid and solid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** Environmental considerations- air spill: Apply water spray or mist to knock down vapors. /Organophosphorus pesticides, liquid and solid, NOS/[Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation. Association of American Railroads, Pueblo, CO. 2005, p. 678] **PEER REVIEWED** DISPOSAL METHODS: Group I Containers: Combustible containers from organic or metallo-organic pesticides (except organic mercury, lead, cadmium, or arsenic compounds) should be disposed of in pesticide incinerators or in specified landfill sites. /Organic or metallo-organic pesticides/[40 CFR 165.9(a) (7/1/90)] **PEER REVIEWED** Group II Containers: Non-combustible containers from organic or metallo-organic pesticides (except organic mercury, lead, cadmium, or arsenic compounds) must first be triple-rinsed. Containers that are in good condition may be returned to the manufacturer or formulator of the pesticide product, or to a drum reconditioner for reuse with the same type of pesticide product, if such reuse is legal under Department of Transportation regulations (eg 49 CFR 173.28). Containers that are not to be reused should be punctured ... and transported to a scrap metal facility for recycling, disposal or burial in a designated landfill. /Organic or metallo-organic pesticides/[40 CFR 165.9(b) (7/1/90)] **PEER REVIEWED** SMALL SPILL: Sweep up material and place in disposable container. ... LARGE SPILL: Clean up spills immediately, observing precautions in Exposure Controls/ Personal Protection section. Vacuum with machines

equipped with high efficiency filters or sweep up material and place in a disposable container. Scrub contaminated area with detergent and water using a stiff broom. Pick up liquid with Oil Dry, cat litter, clay, rags or other absorbent and place in a disposable container. /Orthene Fire Ant Killer 1 (50% acephate)/[The Scotts Company; MSDS for Orthene Fire Ant Killer 1. 10 p. (February 21, 2001). Available from, as of February 22, 2007: http://www.ortho.com/index.cfm/event/media.detail/documentId/a270 c9a6c39f3713713f73edeaef2347] **PEER REVIEWED** Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal.[USEPA/Prevention, Pesticides, and Toxic Substances; Citizen's Guide to Pest Control and Pesticide Safety p.24 (September 1995) EPA 730-K-95-001] **PEER REVIEWED** Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Do cut or puncture other empty pesticide containers made of metal

or plastic to prevent someone from reusing them. Wrap the empty container and put it in the trash after you have rinsed it. [USEPA/Prevention, Pesticides, and Toxic Substances; Citizen's Guide to Pest Control and Pesticide Safety p.25 (September 1995) EPA 730-K-95-001] **PEER REVIEWED** OCCUPATIONAL EXPOSURE STANDARDS:

MANUFACTURING/USE INFORMATION: MAJOR USES: For acephate (USEPA/OPP Pesticide Code: 103301) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./[National Pesticide Information Retrieval System's USEPA/OPP Chemical Ingredients Database on Acephate (30560-19-1). Available from, as of February 9, 2007: http://ppis.ceris.purdue.edu/htbin/epachem.com] **PEER REVIEWED** Insecticide; For use on beans, Brussels sprouts, cauliflower, celery, cotton, cranberries, head lettuce, mint, peanuts, peppers, tobacco, ornamentals, and forests.[Meister, R.T., Sine, C; Crop Protection Handbook Volume 93. Meister Media Worldwide, Willoughby, OH 2007, p. D7] **PEER REVIEWED** Acephate ... is used to control insects and aphids in ornamentals, where it has a reasonably broad spectrum. It is also cleared for use on beans, cotton, head lettuce, celery, soybeans, and bell peppers. It controls parasites of cattle, goats, hogs, horses, poultry, and sheep, where tolerances have been set for milk, eggs, fat, and meat.[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 19811982., p. 4809] **PEER REVIEWED**

Acephate ... is used for household use or golf course spray. /From table/[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1077] **PEER REVIEWED** Organophosphate insecticide currently registered for use on a variety of field, fruit, and vegetable crops (e.g., cotton, tobacco, cranberries, mint); in food handling establishments; on ornamental plants both in greenhouses and outdoors (e.g., nonbearing fruit trees, Christmas trees, and cut flowers); and in and around the home.[USEPA; EPA Interim Registration Eligibility Decision Document. Acephate. EPA 738-R01-013, September 2001. Available from, as of Jan 12, 2007: http://www.epa.gov/pesticides/reregistration/status.htm] **PEER REVIEWED** Contact and systemic insecticide.[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006.., p. 7] **PEER REVIEWED** MANUFACTURERS: Dragon Chemical Corp., 7033 Walrond Dr., Roanoke, VA 24019-7311, (540) 362-3657 Production site: Roanoke, VA 24019-7311[SRI Consulting. 2006 Directory of Chemical Producers-United States. Menlo Park, CA. 2006, p. 779] **PEER REVIEWED** METHODS OF MANUFACTURING: Produced by acetylation of O,O-dimethyl phosphoroamidothioate followed by isomerization.[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 1] **PEER REVIEWED** Acephate may be produced by the acetylation of O,O-dimethylphosphoroamidothioate, (which is prepared from O,O-dimethylphosphorothioic acid chloride and ammonia).[Sittig, M. (ed.) Pesticide Manufacturing and Toxic Materials Control Encyclopedia. Park Ridge, NJ: Noyes Data Corporation. 1980., p. 27] **PEER REVIEWED** Preparation and activity: Magee, US 3716600 and US 3845172 (1973, 1974

both to Chevron).[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006.., p. 7] **PEER REVIEWED** GENERAL MANUFACTURING INFORMATION: The WHO Recommended Classification of Pesticides by Hazard identifies Acephate (technical grade) as Class III: slightly hazardous; Main Use: insecticide.[WHO (2005) The WHO Recommended Classification of Pesticides by Hazard and Guidelines to Classification 2004, International Programme on Chemical Safety, p.26] **PEER REVIEWED** A systemic insecticide of moderate persistence with residual activity lasting about 10-15 days.[Tomlin CDS, ed; Acephate (30560-19-1). In: The e-Pesticide Manual, 13th Edition Version 3.1 (2004-05). Surrey UK, British Crop Protection Council.]