Forensic Science International 197 (2010) 8996

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Forensic Science International

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A chloroform-related death: Analytical and forensic aspects

R.J. Flanagan a,*, D.J. Pounder b
a
b

Toxicology Unit, Department of Clinical Biochemistry, Kings College Hospital NHS Foundation Trust, Bessemer Road, Denmark Hill, London SE5 9RS, UK
Centre for Forensic and Legal Medicine, University of Dundee, Dundee DD1 4HN, UK

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 26 September 2009
Received in revised form 9 December 2009
Accepted 18 December 2009
Available online 13 January 2010

Chloroform is still encountered occasionally in clinical and forensic toxicology, hence knowledge of the
special problems presented in the detection and measurement of this compound in biological specimens
may be required. The aim of this paper is to review the available documentation on this topic in the
context of a chloroform-related death.
Early one morning in February 1999 a 34-year-old female was found dead fully clothed on a path near
to a neighbours garden. Amfetamine intoxication combined with hypothermia was accepted as the
cause of the death in the absence of any other identiable cause. Further investigation 17 months later
revealed a blood chloroform concentration of 31 mg/L and the cause of death was revised to chloroform
poisoning. A murder trial ensued, the indictment specifying forced inhalation as the route of exposure.
The liver chloroform concentration measured 38 months after collection was reported as 1064 mg/kg
and opinions were offered at trial that the autopsy ndings, which included a gastritis, but no evidence of
injury to the inside of the mouth and oesophagus, excluded the possibility of ingestion of a toxic dose of
chloroform. It was asserted that the explanation for the high liver concentration was that the liver had
concentrated chloroform from blood after death against a concentration gradient. At appeal against
conviction 7 years later the conviction was quashed. It was found that the liver concentration should
have been reported at trial as 1 mg/kg. Moreover, chloroform found in the stomach contents (162 mg/kg)
86 months after collection was irrefutable evidence that some, if not all, of the chloroform had been
ingested.
Screening for volatile poisons should always be considered if a cause of death is not immediately
obvious, especially in young people and in known substance abusers. If the presence of an unstable or
volatile analyte is suspected then sample collection, transport, and storage must be performed with the
analysis in mind. Quantitative analysis of all available specimens should proceed forthwith once the
presence of an unstable analyte is established if the cause of death is in doubt or if prosecution may
follow. In the case of chloroform especial precautions are needed: (i) headspace analysis should be
performed at 35 8C to preclude the possibility of artefactual formation from trichloroacetic acid, (ii)
precautions to prevent cross-contamination of biological samples in the laboratory must be taken, and
(iii) interpretation of analytical results must take account of the widespread presence of chloroform in
the environment on the one hand, and that the toxicity of chloroform varies greatly depending on the
circumstances and intensity of exposure on the other.
2010 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Chloroform poisoning
Chloroform analysis
Chloroform stability
Chloroform-biological specimens
Poisoning-volatile substances

1. Introduction
Although long superseded as an analgesic and anaesthetic agent
in clinical practice, chloroform is still encountered occasionally in
clinical and forensic toxicology. Hence knowledge of the analytical
and clinical toxicology of this compound remains important. An

* Corresponding author. Tel.: +44 20 3299 5824; fax: +44 20 3299 5825.
E-mail address: robert.anagan@nhs.net (R.J. Flanagan).
0379-0738/$ see front matter 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.forsciint.2009.12.061

appreciation of the range of pathological features that may be

encountered after chloroform exposure may also be needed.
Chloroform was made initially by passing chlorine gas through
alcohol (ethanol) or diethyl ether, hence its early name of chloric
ether. Such preparations tended to contain a fair amount of alcohol.
Samuel Guthrie (17821848) prepared relatively pure chloroform
by distilling alcohol with chlorinated lime (bleaching powder) in
October 1831. Its properties were reported thus: The action of this
ether on the living system is interesting and may hereafter render it an
object of importance in commerce. Its avour is delicious and its
intoxicating qualities are equal too or surpassing those of alcohol.
Clearly the preparation ingested must have been diluted with

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R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

water and/or alcohol since chloroform (to which 12%, v/v, ethanol
is usually added nowadays as a preservative) is an irritant poison
and as such whitens mucous membranes and reddens skin
(rubefacient action).
The original chloroform preparations or variants were soon
used with therapeutic intent, notably by Formby in 1836 who
found it benecial in the treatment of hysteria [13]. The rst
documented death under chloroform anaesthesia occurred on 28
January 1848 [4]. There were at least 50 such deaths by 1859 [1],
prompting the Lancet commission that invited doctors in Britain
and its colonies to report anaesthesia-related deaths [5]. Similar
concerns were prevalent in the US [6]. The possibility of fatal
complications occurring days after inhalational exposure must be
remembered [7]. Delayed hepatotoxicity due to chloroform
anaesthesia or analgesia during childbirth was reported widely,
for example [811], and was more likely when exposure was
prolonged.
Deliberate inhalation of chloroform in order to achieve
intoxication pre-dated its use in anaesthesia [12]. The American
dentist Horace Wells became dependent on chloroform and
committed suicide by cutting an artery in his groin whilst inhaling
chloroform having been imprisoned after throwing sulfuric acid
over a pair of prostitutes (1848). On 8 February 1848, Arthur
Walker, a young assistant in a drug warehouse in Aberdeen, was
seen to be leaning forward on a counter with his head stooped. He
appeared to be inhaling chloroform vapour from some folds in his
apron. His father was summoned, but when he arrived some
20 min later his son was dead [13]. This was a forerunner of many
thousand accidental sudden snifng deaths worldwide, although
nowadays chloroform itself is rarely encountered in such volatile
substance abuse (VSA)-related deaths [14]. Contributing factors in
sudden VSA-related deaths are thought to be cardiac sensitisation
to circulating catecholamines, vagal inhibition, and respiratory
depression or hypoxia, any of which may promote a fatal
arrhythmia [15,16]. The sudden exposure of the heart and/or
brain to relatively high concentrations of the agent inhaled, which
may be exacerbated by catecholamine release (ght or ight
reaction) if inhalation is forced or if an abuser is surprised, for
example by the unexpected appearance of a parent or of police, are
thought to be factors in some such deaths.
Deliberate inhalation, ingestion, on indeed injection of chloroform in order to commit suicide is well-documented [1,1721], as
is its use/attempted use in the perpetration of serious crime such as
rape, other assault, and murder [7,22] (Table 1). Use of chloroform
in order to commit rape and other felonies was made a criminal
offence in England, Wales and Ireland in 1851 (Prevention of
Offences Act, 13 and 15 Vict. ch. 19, s. 3). Deliberate inhalation to
enhance sexual (self-)gratication has also been described,
sometimes with fatal consequences [28,32,33,36]. Accidental
ingestion of chloroform has occurred, again sometimes with fatal
consequences [1,37].
When ingested the fatal dose of chloroform is much higher and
death occurs much later (generally 56 h post-ingestion) than
reported after inhalation [7]. This is because systemic absorption is
slower than after inhalation and the ingested chloroform has rst
to pass through the hepatic portal system before reaching the heart
and thence the brain. Thus, blood chloroform concentrations are
inevitably lower for a given dose and increase more slowly than
after inhalation. In such cases death is likely to be due either to
indirect causes such as inhalation of vomit, or to the respiratory
depressant effects of the drug.
Non-fatal ingestion or chronic inhalation of chloroform is
usually accompanied by features of hepatic damage that develop
25 days post-exposure and are otherwise similar to those
observed after prolonged anaesthesia [3741]. Signs of hepatic
damage have been reported after occupational exposure to

ambient air chloroform concentrations up to 205 ppm

(1005 mg/m3) [42]. Psychotic behaviour, as in the case of Horace
Wells, and degenerative changes in the brain have also been
described after chronic abuse of chloroform [38].
As noted above chloroform and other volatile substances can
kill quickly, especially if inhaled. Relatively pure chloroform is an
irritant poison and may cause vomiting if ingested. In fatal
poisoning, the smell of chloroform may be noted upon opening the
stomach, but this is by no means a universal nding [27,43].
Famously in the case of Edwin Bartlett, a strong, pungent, ethereal
odour, resembling a combination of chloroform and garlic was
noted on opening the stomach and 111/4 grains (675 mg, 0.48 mL)
of chloroform were found in the stomach contents, although it was
thought there had been much loss of chloroform prior to the
analysis [44]. The stomach showed clear signs of irritation, but
there was no indication of irritation in the mouth, throat, or lungs
[44,45].
A blood chloroform concentration of 200 mg/L has been
reported 10 h after the accidental ingestion of chloroform by a
19-year-old male, who made a full recovery despite requiring
mechanical ventilation for 3 days [37]. Blood chloroform
concentrations attained in anaesthesia are in the range 20
232 mg/L [46], whilst post-mortem blood and liver concentrations
reported in chloroform-related deaths (Table 1) range from 3 to
834 (median 50) mg/L (n = 26) and 6800 (median 87) mg/kg
(n = 16), respectively. However, chloroform is volatile and may be
lost from blood and tissue specimens on standing hence postmortem blood chloroform concentrations, for example, are not
always a reliable guide to the magnitude and duration of exposure.
Moreover, the contribution of other factors such as partial asphyxia
if exposure was by inhalation, at least in part, is unquantiable.
Nowadays the availability of pure chloroform is much
restricted in Western countries as it is an ozone depleter,
although it is synthesised and used in large quantities in industry
as a synthetic intermediate. However, it may be still present in the
environment in small quantities due, for example, to chlorination
of organic matter in public drinking water supplies in some
countries, including the UK, and in swimming pools [47].
Chloroform is still listed in the British Pharmacopoeia as
chloroform water in various strengths and chloroform spirit
(chloroform:ethanol:deionised water 5 + 855 + 95) and is still used
in some countries as a carminative and as a avouring agent and
preservative in a number of over-the-counter preparations. Its use
is banned in the US, however, as it is a carcinogen.
2. Case report
2.1. Case history and medical examination
At 08:22 h on 8 February 1999 a 34-year-old woman was found
dead, lying supine, fully clothed outside on a common path near a
neighbours garden. A forensic pathologist attended the scene at
11:20 at the request of police. A limited examination of the body
revealed no obvious injury and that rigor mortis was just beginning.
The temperature adjacent to the body was 0 8C. She had been last
seen alive at 21:20 on 7 February. The body was taken to a mortuary
and the examination continued at 13:35. The body was stripped
naked. The procurator scal (state prosecutor), on the advice of the
pathologist and police, thought the death not suspicious and ordered
an autopsy, which commenced immediately.
The examination revealed trivial external injuries (Table 2), but
no evidence of natural disease that could account for death. No
injection marks were noted. There were no conjunctival or facial
petechiae. The cause of death was given as undetermined pending
toxicological analysis. The possibility that hypothermia may have
played a part in the death was raised (the night-time temperature

R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

91

Table 1
Post-mortem chloroform concentrations in blood, brain, liver, and stomach contents after acute poisoning in man.
Age (year),
sex

Blood
(mg/L)

Liver
(mg/kg)z

Stomach
contents (mg/kg)

Brain
(mg/kg)z

30, M
24, F

60
43

44

49

18, F

17

25

55

?
?

48
10

37

39
7

45, M

36

71

143

16, F

36

72

94

52, M
52, M
17, M

40
30
51z

86
16
201

<1
<1
7130

156
2650
113

29, M

123

540

133

131
85124#
120
180
3

280

64
116

298

24
800

7
23
<1

21

54
258

3
46
770

33

88

16

124

33, M

274

178

63

113

28, M

47

188

74

38, M
3, M
6, F
8, F
16, F
16, F
13, F

33
102
5
73
86
115
834

40
71
23

23,
31,
54,
52,
72,
78,
52,

F
F
F
M
F
M
M

39, F

z
#

Comment

Reference

Forced inhalation. Homicide

Forced inhalation. Homicide.
Analysis 10 days after death
Forced inhalation. Homicide.
Analysis 5 days after death
Suicide by inhalation from plastic bag
Deliberate inhalation; died after
12 h in hospital. Accident
Meprobamate overdose, probable
suicide. Source of chloroform unknown
Deliberate inhalation of chloroform
and diethyl ether; ethanol also
present. Accident. Analysis at
least 3 days after death
Forced inhalation and ingestion during
attempted rape. Homicide
Deliberate inhalation. Suicide
Deliberate inhalation. Suicide
Inhalation and ingestion. Femoral
blood 51, heart blood 194, intestinal
contents 27,000, urine 2 mg/L;
kidney 60, lung 66 mg/kg
Forced inhalation (?) and perhaps
ingestion. Kidney 124 mg/kg. Homicide
Forced inhalation? Kidney 65 mg/kg. Homicide
Forced inhalation. Homicide
Deliberate inhalation. Accident
Ingestion? Suicide
Forced inhalation. Homicide
Forced inhalation. Homicide
Forced inhalation. Left heart blood 280, right
heart blood 200, urine 1.4 mg/L; kidney 250,
lung 190 mg/kg. Homicide
Deliberate inhalation; evidence of chronic
abuse. Kidney 35 mg/kg. Accident
Deliberate inhalation. Urine 5 mg/L; kidney 58,
lung 73 mg/kg. Suicide
Deliberate inhalation. Centrilobular hepatic
necrosis. Urine 2 mg/L; kidney 144 mg/kg. Suicide
Deliberate inhalation. Accidental sexual asphyxia
Forced inhalation. Homicide
Forced inhalation. Homicide
Forced inhalation. Homicide
Forced inhalation. Homicide
Forced inhalation. Homicide
Rape victim. Urine 10, bile 148 mg/L.
No information on route of exposure

Kim et al. [23]

Bonnichsen and Maehly [17]
Bonnichsen and Maehly [17]
Bonnichsen and Maehly [17]
Bonnichsen and Maehly [17]
Bonnichsen and Maehly [17]
Bonnichsen and Maehly [17]

Kaempe and Dalgaard [24]

Giusti and Chiarotti [18]
Giusti and Chiarotti [18]
Ifand and Ramme [25]

McGee et

al. [26]

McGee et al. [26]

Cooke and Pounder [27]
Allan et al. [28]; Farrow [29]
Kohr [19]
Nashelsky et al. [30]
Nashelsky et al. [30]
Vendura et al. [31]

Harada et al. [32]

Nadjem and Logemann [21]
Meichsner et al. [20]
Byard et al. [33]
Rie et
al. [34]
Rie et al. [34]
Rie et al. [34]
Rie et al. [34]
Rie et al. [34]
Gaillard et al. [35]

Wet weight of tissue.

Range (six samples).

was recorded as down to 4 8C), although there were no

corroborative autopsy ndings. The autopsy report documented
dried vomit around both nostrils and on the lower right side of the
cheek, conrming a note made at the scene that recorded a small
amount of tomato-stained vomitus present around the nostrils and
the right side of the mouth. The lesser curve of the stomach showed
evidence of acute haemorrhagic gastritis, with no ulcers or

erosions. The stomach contents comprised 50 mL of partially

digested food, apparently pizza, with no identiable tablets or
capsules. No unusual smell was noted on opening the stomach. The
bladder was empty. There was no note made at the scene or at
autopsy of any area of apparent drying of the lower lip on the left
side, although later this was observed on contemporary photographs.

Table 2
Evidence of recent injuries recorded at the post-mortem examination.
No.

Injury

1
2
3
4
5
6
7

Faint blue bruise, 1.5  1 cm, on the front of the right arm, located 15 cm below the top of the shoulder.
Slightly raised blue bruise, 0.5  1.2 cm, located on the left upper eyelid in the outer half.
Speckled pink intradermal (supercial) bruise, 1.5  0.3 cm, located on the front of the left shoulder, 15 cm to the left of the anterior midline.
Very faint orange-based abrasion, 0.2  0.2 cm, located on the point of the chin, 1 cm to the left of the anterior midline.
Faint blue bruise, 0.3  0.5 cm, located on the lateral (outer) aspect of the left thigh, 30 cm below the level of the anterior superior iliac spine.
Very faint bluish bruise, 0.3  0.5 cm, located on the lateral aspect of the left thigh, 34 cm below the level of the anterior superior iliac spine.
Triangular shaped blue bruise, 3  3 cm, located on the lateral aspect of the dorsum of the right foot immediately below the lateral malleolus.

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R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

2.2. Toxicological investigations

The toxicological analyses were restricted to testing for
common drugs of abuse and ethanol. Vitreous humour was not
sent for biochemical analysis. Cannabinoids were detected in blood
(site of collection not specied) by gas chromatographymass
spectrometry, but no quantication was attempted. The blood
amfetamine concentration was reported as 0.05 mg/L. No ethanol
or other common drugs were detected. The liver sample was sent
to a further laboratory for testing for pesticides, but nothing was
found. Thorough microscopic examination of the main organs of
the body, including liver and kidney, and the brain disclosed no
signicant pathological or histological changes, although occasional contraction band necrosis was noted in muscle from the
right ventricle. Given this additional information the cause of
death was expressed guardedly as presumed hypothermia, due to
acute amphetamine intoxication with chronic drug misuse as a
signicant contributory factor. Information supplied by the
partner of the deceased, a 31-year-old male, was that she was a
heavy smoker, was not known to drink alcohol, and used some 3 g
amfetamine and 7 g cannabis resin, mainly at weekends.
Some 17 months later, a telephone call to police from a
registered police informant, an associate of the partner of the
deceased, suggested that insulin and chloroform had been used in
the murder of the deceased. Blood from the deceased (site of
collection not stated), which had been retained at autopsy for
toxicological analysis and stored in an unopened plastic Sterilin
screw-capped tube, was found to contain chloroform. The blood
chloroform concentration was reported as 31 mg/L. The vitreous
humour was also found to contain chloroform, but the concentration was not measured. The liver and stomach contents were not
tested for chloroform; the brain had been xed in formalin and so
was unavailable for testing.
In the light of this additional information the pathologist reevaluated the autopsy ndings, and photographs taken prior to
autopsy, and advised that the cause of death should be changed to
chloroform intoxication. The written opinion was offered that a
dried red mark on the lower lip on the left side could represent the
effects of direct contact of chloroform onto the lip; a bruise to the
front of the left shoulder could have been produced by the
application of pressure through clothing during forcible gripping;
and a bruise on the inner aspect of the right upper arm could have
been produced by forceful digital pressure. The two latter
comments were qualied by stating: it must be stressed, that
neither of these injuries are entirely specic.
2.3. The trial
Based on this new information the partner of the deceased was
arrested and charged with murder. The charge against him
proceeded principally on the evidence of two associates of the
accused (defendant) who alleged that the accused had confessed to
them that he had forcibly administered chloroform to the deceased
by holding it over her nose and mouth and causing her to inhale it.
The indictment libelled specically that he had rendered the
deceased unconscious by forcing her to inhale chloroform and then
placed her outside where she froze to death. Under Scots law a
criminal charge cannot be proved without corroboration. This
means that there must be evidence from two or more sources
pointing to the accused as the perpetrator of the crime. In this case
the main evidence related to a confession made by the accused to
two associates. It follows that the accused presented the source of
the evidence and although the confession was allegedly made to
two persons there was only one source, namely the accused.
However, where a confession made by an accused person contains
details of a crime that could only be known by its perpetrator then

these details (referred to in law as special knowledge) provide the

necessary corroboration of the essential facts that a crime has been
committed and that the accused is the perpetrator. This placed an
obligation on the prosecution to prove that chloroform had entered
the body of the deceased by the method disclosed in the alleged
confession.
Re-analysis of the blood sample from the deceased in an
independent laboratory some 3 years after collection conrmed
the presence of amfetamine and chloroform (concentrations 0.08
and 22 mg/L, respectively). The analytical methods used were not
reported. The differences between these results and those of the
prosecution did not affect the clinical interpretation of the ndings.
The defence also obtained the services of one of the authors (RJF),
who later gave evidence at trial. Following disclosure and review of
the laboratory records, the analysis of chloroform was queried
since (i) chloroform is not easily available in quantity nowadays,
(ii) vitreous humour had been analysed, but the analysis had not
been reported the chromatograms suggested possible sample
contamination with 1,1,1-trichloroethane, and (iii) if the chloroform analysis had been performed by headspace gas chromatography (HS-GC) at 65 8C (standard HS-GC conditions for ethanol),
there was the possibility that decomposition of trichloroacetic acid
(a minor metabolite of 1,1,1-trichloroethane), if present in the
samples analysed, could have given rise to chloroform.
It was suggested that liver, stomach contents, and any other
remaining samples be analysed for chloroform (HS-GC, 35 8C to
obviate the risk of artefactual chloroform formation from
trichloroacetate [48]) in order to facilitate clinical interpretation
of the blood chloroform concentration, 31 mg/L being within the
range reported in fatal chloroform poisoning on the one hand, and
within the range associated with full recovery after chloroform
anaesthesia, for example, on the other. A further factor was the
possible loss of chloroform from the blood sample on storage
information was supplied suggesting that liver and stomach
contents samples had been stored at 20 8C since collection.
In the event, the results of the analysis of the liver sample alone
became available to both prosecution and defence experts during
the trial. The liver chloroform concentration was reported as
1064 mg/kg (HS-GC, 35 8C), i.e. the liver apparently contained
chloroform at a concentration more than 30 times that of the
blood. The liver had weighed 1590 g at autopsy and if uniform
distribution of chloroform throughout the liver could be assumed,
this organ contained about 1.5 g chloroform (0.1% of liver weight).
In the view of all the experts the cause of death was clearly
chloroform poisoning, the contribution of hypothermia being
negligible at best. There were no signs of hepatocellular damage at
post-mortem suggesting that chloroform exposure was acute
rather than chronic or acute-on-chronic, i.e. that the deceased had
not abused chloroform in the recent past. However, the defence
advanced the proposition that the medical and toxicological
evidence supported ingestion rather than inhalation as the primary
method by which the chloroform was taken into the body. It was
specically argued that the reported liver chloroform concentration of 1064 mg/kg could not be explained by inhalation alone.
The prosecution countered the argument that ingestion rather
than inhalation was the primary method of chloroform administration by advancing three propositions: (i) that there were
autopsy ndings corroborative of inhalation of chloroform, (ii) that
the autopsy ndings that would be expected if chloroform had
been ingested were not present, and (iii) that the toxicological
ndings, including those in the liver, were consistent with
inhalation without ingestion of chloroform. The trial judge noted
in his charge to the jury that an acceptance that the chloroform was
ingested would mean that the jury could not convict of the charge.
So the issue of whether the chloroform had denitely been inhaled,
and thus that ingestion could be reasonably excluded, was critical.

R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

The prosecution pathologist was unequivocal in evidence that

chloroform had been inhaled and not ingested, stating: There was
absolutely no evidence at autopsy to support the hypothesis that
the chloroform was ingested. The small area of drying of the lower
lip, and a slightly reddish discolouration extending from the
bottom of the mouth that was also possibly slightly swollen as
seen in photographs of the deceased were regarded as positive
evidence of inhalation of chloroform as a result of the application
of a chloroform-soaked cloth. The mark to the lip was acknowledged as potentially due to post-mortem drying and the reddening
of the chin area as non-specic. The balanced advice was given
that, although non-specic, these ndings could be due to a
chloroform-soaked pad, for example, being placed on the face. This
fair presentation of non-specic ndings to the face being
consistent with the prosecution proposition of the placement of
a chloroform-soaked rag over the nose and mouth was not
matched with an equally fair acceptance that the non-specic
nding of an acute haemorrhagic gastritis could have been due to
the ingestion of chloroform.
With regard to the anticipated effect of liquid chloroform on the
oesophagus and stomach, it was stated in Court that chloroform
was a corrosive poison and that damage to the oesophagus and a
blackened stomach would be found at autopsy if exposure had
occurred by ingestion. Moreover, it was claimed that the
pathologist would certainly expect to smell chloroform on opening
the stomach. However, the literature does not support these
assertions. Whilst the statements reect one extreme of the
spectrum of possible ndings reported following ingestion of
chloroform, they do not fairly reect the usual or the full range of
possible ndings [43].
At trial the interpretation of the post-mortem toxicology,
particularly the concentration of chloroform in the liver relative to
that of the blood, proved problematic. The concentration of
chloroform in the liver as reported was remarkable and
unexpectedly high when compared with the literature (Table
1). The proposition of the Crown expert witnesses, that the
unexpectedly high chloroform concentration in the liver could be
explained by inhalation followed by post-mortem redistribution
from blood to liver, i.e. that the liver had acquired chloroform from
blood after death against a concentration gradient, has no scientic
foundation whatsoever. Nevertheless, in the event on 22 April
2002 the accused was convicted and sentenced to life imprisonment with a minimum tariff of 18 years.
2.4. The appeal
Immediately post-trial the defence sought leave to appeal
primarily on the grounds that the presentation of the scientic
evidence by the prosecution witnesses with respect to the

93

possibility of ingestion of chloroform by the deceased was fatally

awed and hence was seriously misleading on a critical matter.
Prior to the appeal hearing the liver chloroform concentration
reported at trial (1064 mg/kg) was found to be wrong, the true
concentration being 1 mg/kg. The reason for this error was never
made clear, but it would appear to have been confusion between
mg/mL, mg/L, mg/g, and mg/kg. For liquids and solids having a
relative density of ca. 1 all these units are different ways of
expressing the same thing, but the liver concentration (calculated
in terms of mg/g wet weight of tissue) was multiplied by 1000
before it was reported. Be this as it may, subsequently chloroform
was measured in the stomach contents by order of the Court and
was found to be present at a concentration of 162 mg/kg, i.e. some
5 times the blood concentration. The chronology of the
chloroform measurements in the samples from the deceased is
given in Table 3.
At the appeal hearing some 7 years post-conviction, the
conviction was quashed and the Crown were refused leave for a
second prosecution [49]. The prosecution pathologist was criticised for not advising the trial court that his failure to detect any
smell of chloroform at post-mortem on opening the stomach and
the absence of noteworthy changes to the inside of the mouth and
oesophagus of the deceased did not rule out the ingestion of
chloroform and that the presence of a gastritis, although an
entirely non-specic nding, could have resulted from the
ingestion of chloroform. Having had the opportunity to consider
these criticisms, the prosecution pathologist opined that autopsy
examination revealed the presence of acute haemorrhagic gastritis, while this is a non-specic nding it could have been caused by
ingestion of chloroform, and conceded that chloroform is an
irritant to the lining of the gut, but I was in error to suggest that it is
corrosive in the sense that bleach is corrosive. Hence, it was
acknowledged that ingestion as a route of administration could not
be excluded on the basis of the anatomical ndings.
Somewhat offsetting this concession was an apparently
strengthened view that the marks to the face were the result of
the application of a chloroform-soaked cloth: the marks noted
upon the lips at the initial autopsy, though small are consistent
with chemical induced injury and strongly suggest that at some
stage a cloth soaked with chloroform has been applied to the
mouth and nose. The scientic rationale behind this apparent shift
in opinion was not made clear.
Following inhalation of chloroform, some chloroform can be
expected to be found in the stomach contents if only as a result of
diffusion from the blood into the stomach in life. Additionally,
during inhalation of chloroform the swallowing of air and saliva
contaminated with chloroform will introduce chloroform into the
stomach. There are limited data on the extent to which the
stomach may contain chloroform in cases of presumed chloroform

Table 3
Summary of chloroform analytical data.
Sample

Container

Storage

Opened/thawed
before analysis?

Months before
analysis

[Chloroform]

Blood

Plastic screw-capped
Sterilin vial

10 days, 28 8C,
subsequently 15 to 20 8C
until rst analysis,
thereafter variable

No

17

31 mg/L

Yes

36

22 mg/L (different laboratory)

Vitreous
humour
Liver

Plastic

Yes

17

Not measured

Yes

38

1.06 mg/kg (1064 mg/kg at trial)

Stomach contents

Plastic
screw-capped vial

10 days, 28 8C,
subsequently 15 to 20 8C
10 days, 28 8C,
subsequently 15 to 20 8C
until sent for pesticide
analysis, thereafter variable
10 days, 28 8C,
subsequently 15 to 20 8C

No

86

162 mg/kg

Plastic

94

R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

inhalation, but the available data suggest that the chloroform

concentration in stomach contents may be up to twice that
reported in blood (Table 1). In the present case the concentration
in stomach contents was reported as 162 mg/kg and the
concentration in blood as 31 mg/L, an approximately 5-fold
difference, without attempting to correct for any storage timerelated losses of chloroform.
At appeal defence experts opined that the full analytical results
indicated that there had been ingestion of chloroform. The
available data were, on the one hand consistent with the ingestion
of chloroform without inhalation. On the other hand, a combination of both ingestion and inhalation of chloroform was a
possibility, but inhalation of chloroform alone could be excluded
with reasonable certainty. On the other hand, the prosecution
suggested that any ingestion of chloroform could be accounted for
by coincidental ingestion of chloroform from a soaked pad at the
time of inhalation. The presence of contraction band necrosis in
muscle from the right ventricle was also said to be consistent with
sudden death due to chloroform inhalation, but this phenomenon
is non-specic and has also been observed in metamfetaminerelated deaths, for example [32]. In the event, however, there was
general consensus that the autopsy ndings did not assist in
resolving the issue of whether the chloroform had been inhaled, or
ingested.
If the marks to the face were to be interpreted as being the
result of the application of a chloroform-soaked pad or similar
item, with the inference that there was some inhalation of
chloroform, then their extent did not suggest that there was
vigorous resistance on the part of the deceased. Such vigorous
resistance might be expected to produce orid marks over the face
reecting a combination of abrasion and chemical burn [26]. The
minimal lesions seen in this case would be consistent with
inadvertent contact between a chloroform-soaked cloth and the
face, of a type which was seen when chloroform was used as an
anaesthetic agent. This leaves open the possibilities that any
inhalation of chloroform was voluntary, or alternatively was
achieved through threat of violence or trickery, or when the
deceased was already incapacitated.
3. Discussion
3.1. Analytical considerations
Analyses for solvents and other volatiles in life are normally
performed using either anticoagulated whole blood, or expired air.
Whole blood is preferred to plasma because of its greater lipid
content and also because the simple act of removing plasma
enhances the risk of loss of volatiles. The blood:plasma concentration ratio for chloroform is reported as averaging 4.0 at a blood
chloroform concentration of 75 mg/L [50]. In post-mortem work of
course, use of whole blood is the norm, peripheral blood being the
specimen of choice unless multi-site sampling is an option [51].
Plasma chloroform concentrations in otherwise unexposed
individuals are generally less than 0.1 mg/L, but unexplained
ndings of 1.74 mg/L have been reported in 3 of 25 subjects
studied [52]. In this context, a further possible source of
chloroform on headspace gas chromatography is from thermal
decomposition of trichloroacetic acid at temperatures of the order
of 60 8C [48]. Trichloroacetic acid is a metabolite of several
compounds including the solvent trichloroethylene and the drugs
chloral hydrate, dichloralphenazone, and triclofos. Trichloroacetic
acid has a half-life in blood of 35 days and thus may be detected
for a relatively long time after exposure to, or ingestion of, a
precursor. Trichloroacetic acid plasma concentrations of up to
40 mg/L have been reported after exposure to trichloroethylene
vapour (194 ppm, 5 h) [53].

The widespread presence of chloroform in the environment and

the sensitivity of modern analytical methods mean that measurement of chloroform in all available biological samples (HS-GC,
35 8C unless there is compelling evidence that chloroform is the
only possible analyte) is necessary in order to help establish the
magnitude and possible route of exposure if chloroform poisoning
is suspected. As with all volatile compounds, special precautions
are necessary in the collection, transport, and storage of such
specimens not only to minimise loss of analyte(s), but also to
minimise the risk of cross-contamination with chloroform or other
volatiles [51,54]. Such contamination may arise during sample
transport if products sent for analysis are packaged together with
biological samples, and also during storage in the laboratory.
Chloroform was widely used in analytical laboratories as an
extraction solvent, for example, and although used much less
frequently than in previous years, the possibility of contamination
from this source must be borne in mind, especially if the analysis is
delayed. Chloroform has a signicant vapour pressure at 0 8C
(7.8 kPa) and even at 20 8C (2.4 kPa).
Rie et al. [34] reported total loss of chloroform from blood
stored at room temperature in polyethylene as well as in glass
vessels over 32 days (4 8C, 60% loss in polyethylene vessels and 40%
loss in glass vessels; 20 8C, 40% loss in both types of vessel). They
concluded that most chloroform was lost as a result of opening of
the vessels. Losses may be minimised by opening the vessel when
cold (4 8C) [54]. Gettler and Blume [55] reported an 82% loss of
chloroform from tissue specimens after 42 days, and although glass
vessels will have been used, the paper is silent as regards the
storage conditions, headspace, etc. On the other hand, Allan et al.
[28] reported 60% loss of chloroform after storage of a blood
sample for 1 year (4 8C) in its original glass bottle. In the present
case, re-analysis of the blood sample in a second laboratory 19
months after the initial analysis (36 months after collection, Table
3) revealed an apparent 30% loss of chloroform. However, given the
difculties of assay calibration and quality control inherent in the
analysis of volatiles such as chloroform, when calibration and other
solutions have to be freshly prepared every time an analysis is
performed [54], this difference could well be within the limits of
analytical variation.
The possibilities of loss of analyte on the one hand, and sample
contamination on the other, mean that any analyses for volatiles
should be performed as quickly as possible and with all due
precautions once samples are received in the laboratory [54]. Glass
sample collection vessels with tightly tting closures (preferably
lined with aluminium foil) are ideal, but today health and safety,
cost, and other factors mitigate against the use of glass vessels
routinely. This being said, Gaillard et al. [35] performed sample
collection directly into 30-mL borosilicate glass asks with selfcrimping screw tops that were analysed within 24 h of collection
the blood chloroform concentration is the highest on record in a
chloroform-related death (Table 1).
Plastic containers of course are not ideal for volatiles analysis
since there is the likelihood of loss of analyte by absorption in, or
diffusion through, the walls of the container, especially if storage is
prolonged. Whatever container is used the size of the headspace
above the sample in the container and the temperature at which
the sample is opened are important factors inuencing loss of
volatiles prior to any analysis [54,56]. This being said, solid tissue
such as liver is less likely to lose volatile analyte if stored at 20 8C
than blood because of its higher lipid content. Moreover, an
analysis for volatiles can be performed by transfer of a portion of
frozen tissue into a GC headspace vial, which is then sealed before
the tissue is allowed to thaw, whereas blood normally requires
thawing and mixing prior to sampling.
Given the 1886-month delays in analysing the samples from
the deceased (Table 3), it is likely that blood, vitreous humour,

R.J. Flanagan, D.J. Pounder / Forensic Science International 197 (2010) 8996

liver, and stomach contents all lost chloroform prior to the

analyses. At trial the very high liver chloroform concentration
reported lead to chloroform poisoning being accepted as the cause
of death by all parties. At appeal the revised (1000-fold lower) liver
chloroform concentration was clearly incompatible with the much
higher concentrations found in blood and stomach contents. On
one hand it had been maintained that the liver sample had
remained sealed and then stored at 20 8C until analysed for
chloroform prior to the trial, but it was conrmed that the sample
container was leaking when received originally in the laboratory,
and that the whole sample had been sent to another laboratory for
pesticide analysis (December 2000). Whilst there, it had been
allowed to thaw completely. The liver chloroform concentration
reported at appeal was therefore discounted as unreliable.
In contrast to the liver sample, the blood sample used for
chloroform measurement and the stomach contents had been
stored in plastic containers under similar conditions until the time
of analysis as far as could be ascertained (Table 3), although no
storage records or freezer temperature records were available to
the Court. There are no available scientic data on the relative
losses of chloroform from blood as opposed to stomach content
samples under such conditions. The interval between autopsy and
sample analysis was 5 times greater for the stomach contents than
for the blood, and if, as is reasonably likely, loss of chloroform in
such circumstances is time dependant, then there is an expectation
that any fall in concentration in chloroform in blood would be
mirrored by an even greater fall of concentration of chloroform in
stomach contents, notwithstanding any physical factors such as
the possibility of freezer malfunction during the extended period
of storage.
3.2. Cause of death
Although the acceptance of chloroform poisoning as the cause
of death was rendered less certain by the unreliability attached to
the liver measurement, chloroform poisoning on balance still
seems more likely than the cause of death accepted initially, i.e.
hypothermia associated with amfetamine use. The concentration
of chloroform in the blood of the deceased was within the range
found in chloroform-related fatalities (Table 1). Moreover, (i) there
was no trauma sufcient to account for death, (ii) there was no
natural disease sufcient to account for death, (iii) hypothermia as
a cause of death must necessarily be secondary to some other
incapacitating condition, and (iv) amfetamine intoxication was
only a remote possibility as a cause of death and was entertained
originally because of the absence of any more likely alternative.
It should, however, be noted that the possibility of insulin
poisoning had been mentioned when the possibility of chloroform
poisoning had been raised. This possibility was not pursued since
no injection marks were noted at the post-mortem examination
and of course insulin could not be tested for at that juncture.
Secondly, although cannabis metabolites were detected in blood
from the deceased, quantitation was not performed. There is a
report of cardiovascular fatalities associated with cannabis use
[57]. Thirdly, although the deceased was said not to use alcohol,
she did work as manager of a public house. If ethanol intoxication
had been a contributory cause to her falling unconscious then
ethanol elimination could have continued until death rigor
mortis was just beginning at 11:20 h on the day she was found and
the rectal temperature at 13:25 h was 20 8C. Finally, the use of
poppers (amyl nitrite or other nitrites that can be abused by
inhalation) was mentioned at interview by the accused. No
evidence of use of nitrites by the deceased was available from the
analysis of biological samples, and such deaths as have been
reported in association with these compounds are the result of
ingestion [58].

95

4. General discussion
It is at rst sight surprising that the fact that the death was
possibly chloroform-related was only realised 17 months after the
discovery of the body since a sensitive test to detect exposure to
trichloro-compounds has been available since 1914 (Fujiwara
test). Indeed the availability of simple methodology to detect
exposure to chloroform and to chloral hydrate led to a marked
decline in the use of these compounds for criminal purposes.
Nowadays of course HS-GC provides simple methodology for
detection, identication, and measurement of chloroform and
many other volatile poisons, some more common than others
[14,54]. That such methods are not used in difcult cases as a
matter of course is a consequence of the restructuring of toxicology
laboratories to deal with common problems (alcohol and other
drugs of abuse on the one hand, and drugs commonly used in selfpoisoning on the other) in order to contain costs on the assumption
that the circumstances will always dene the analysis required.
Toseland [59] drew attention to the folly of this approach. Lawler
[60], ironically writing from Manchester, the home of serial
homicidal poisoner Harold Shipman, emphasized the need to keep
an open mind and to pursue toxicological investigation when
confronted with an unascertained cause of death.
Once the presence of the chloroform in the blood sample from the
deceased was conrmed, neglect of the need to promptly analyse all
the remaining samples (HS-GC, 35 8C) in order to provide as much
evidence as possible as to the magnitude and possible route(s) of
exposure led to much debate and difculty. Of course, it now seems
that the value of the liver sample had been compromised before it
was analysed for chloroform prior to the trial. Be this as it may, the
presentation of the erroneous liver measurement at trial (i) diverted
attention from other possible causes of death, and (ii) generated the
entirely erroneous hypothesis that the liver had somehow managed
to concentrate chloroform out of blood after death against a
concentration gradient. This error was compounded by a one-sided
representation of the pathological features to be expected after
ingestion of chloroform.
5. Conclusions
In the case described, the fact that the likely cause of death,
chloroform intoxication, escaped detection initially and then that
the indictment specied forced inhalation as the route of exposure
caused many difculties. The opinions offered at trial that the
autopsy ndings excluded the possibility of ingestion of a toxic dose
of chloroform were incorrect. The chloroform found in the stomach
contents 86 months after collection was irrefutable evidence that
some, if not all, of the chloroform had been ingested. Screening for
volatile poisons should always be considered if a cause of death is not
immediately obvious, especially in young people and in known
substance abusers. If the presence of an unstable or volatile analyte
is suspected then sample collection, transport, and storage must be
performed with the analysis in mind. Quantitative analysis of all
available specimens should proceed forthwith once the presence of
an unstable analyte is established if the cause of death is in doubt or if
prosecution may follow.
Acknowledgement
We thank Mr JD Keegan QC for helpful criticism of the
manuscript.
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