CADMIUM AND INORGANIC COMPOUNDS

CAS number: 7440-43-9 — Elemental cadmium

Empirical formula: Cd — Elemental cadmium

RECOMMENDED BEI®
Determinant Sampling Time BEI Notation
Cadmium in urine Not critical 5 µg/g creatinine B
Cadmium in blood Not critical 5 µg/L B

Properties cadmium or renal tubular dysfunction from other

Cadmium is a soft, silvery, and ductile metal with
a melting point of 321°C and a boiling point of
(1,2)
765°C. Solubility varies widely among the large
(1)
number of cadmium compounds.
Absorption
Cadmium is absorbed via the lungs and the
gastrointestinal tract. In the workplace, the lungs are
the major route of absorption of aerosols, dusts, and
fumes. Gastrointestinal absorption, the major route
of cadmium entry from environmental (nonoccupa-
tional) sources, can contribute significantly to expo-
sure in the workplace if hands and food become
(1,2)
contaminated.
Pulmonary
Pulmonary uptake ranged from 0.1% to 50% of
(3,4)
inhaled cadmium. The degree of absorption
depended upon particle size and solubility of the
cadmium compound.
etiologies resulted in increased renal elimination of
cadmium.
Distribution and Biochemical Interactions
Cadmium in plasma and tissues was bound to
metallothionein, a small protein with a molecular
weight of approximately 6500, and to certain high
molecular-weight proteins.
(1–4)
In blood, cadmium
was present mainly in erythrocytes, bound to metal-
lothionein. At low exposure, 40% to 80% of retained
cadmium was stored in the liver and kidneys and
20% in muscle.
(2–5)
In the kidney, the highest
concentration of cadmium was in the cortex. With
increasing exposure, cadmium retention decreased
in the kidney and increased in the liver.
Metallothionein production was stimulated by
cadmium and other bivalent metals, such as zinc,
copper, and mercury. When an insufficient amount
of metallothionein is available to bind the cadmium,
toxicity may occur, possibly as a result of cadmium
interference with zinc-dependent enzymes.
(2)

Dermal
No human data on dermal absorption of
cadmium were found.
Gastrointestinal
Gastrointestinal absorption in healthy humans
ranged between 3% and 7% of ingested cadmium. It
increased with nutritional deficiencies of calcium,
iron, or protein to as high as 20%.
(1,4)
Elimination
The estimated biological half-life of cadmium is
(2–8)
between 10 and 30 years. The main route of
elimination in humans is renal. Cadmium in feces is
mainly unabsorbed, ingested cadmium; fecal excre-
tion of absorbed cadmium is a minor route of elimi-
(3)
nation in humans. The total daily excretion repre-
sented only about 0.01% to 0.02% of the total body
(2)
burden of cadmium. Renal tubular damage from
2001 © ACGIH
Possible Nonoccupational Exposure
Cadmium is widely spread in nature. It is closely
related to zinc in its chemistry and is present in
(1,2)
nature wherever zinc is found. Cadmium content
(2)
in most foodstuffs is about 0.005 to 0.1 mg/kg.
Oysters and beef kidney contain 0.1 to 0.5 mg of
cadmium/kg. Rice in some areas of Japan may
contain about 1 mg of cadmium/kg, a result of
industrial contamination. Shellfish in Japan, the
United Kingdom, and New Zealand are also rich in
cadmium. In areas without industrial contamination,
an adult ingests 10 to 60 µg of cadmium daily, from
(2)
which 0.5 to 1.5 µg is absorbed. In contaminated
areas of Japan, the average daily intake is as high
as 400 µg.
Smoking is a significant source of cadmium
exposure. Each cigarette contains about 1 to 2 µg
cadmium, of which 25% to 50% is retained in the
(2–4)
lungs.
Cadmium & Compounds BEI – 1
TLV–TWA
® half-life reflects whole-body clearance. Lauwerys
The TLV –TWA for cadmium and its compounds
3
was reduced in 1993 to 0.01 mg/m for total dust
3
and to 0.002 mg/m for its respirable fraction (both
expressed as cadmium). The purpose of this action
was to reduce the potential for lung cancer and
preclinical signs of kidney dysfunction (β2-micro-
(9)
globulin excretion above 290 µg/L).
Summary
Measurement of cadmium in urine is the most
widely used biological measure of chronic exposure
to cadmium. However, it may provide no information
on integrated exposure during the first year of
exposure. Measurements of cadmium in blood are
an indicator of recent exposure to cadmium. Moni-
toring in blood should be preferred during the initial
year of exposure and whenever changes in the
degree of exposure are suspected. Interpretation of
biological monitoring data, particularly for individual
workers, requires a program of periodic biological,
medical, and environmental monitoring.
CADMIUM IN URINE
Analytical Methods
The most widely used method for determination
of cadmium in urine is atomic absorption spectro-
photometry (AAS) with electrothermal atomization
(10–18)
(ETA). Correction for analytical background is
needed due to high nonspecific absorption. Other
methods lack sensitivity or practicality. Measure-
ment of creatinine is required.
Sampling and Storage
The sampling time is not critical because of the
long elimination half-life. Risk of contamination is a
(10)
serious problem, however. Urine specimens
should be collected outside the workplace in acid-
cleaned plastic or glass bottles. Contact with colored
plastic and rubber should be avoided. Samples
stored frozen at –20°C must be mixed thoroughly
(13)
before an aliquot is taken for analysis.
Biological Levels
Without Occupational Exposure
Cadmium concentration in urine is related to
chronic cadmium exposure. It increased with age,
cigarette smoking, and intake from a polluted
(1–4)
environment. In most countries, including the
United States, the average concentration of
cadmium in urine was between 0.5 and 1.0 µg/L,
(19–21)
ranging from 0.02 to 4.5 µg/L.
Kinetics
The estimated elimination half-life of cadmium in
2 – Cadmium & Compounds BEI
human urine was between 10 and 30 years. This
(22)
described three phases of elimination. During the
first phase, cadmium accumulated in the renal
cortex, binding to metallothionein. No saturation of
binding sites occurred and cadmium was excreted in
urine, probably bound to metallothionein. The excre-
tion reflected cadmium levels in the kidney and total
body burden and was affected by past exposures
and possibly by a recent high exposure. The second
phase occurred when integrated exposure resulted
in saturation of binding sites, followed by an
increase of cadmium concentration in urine. The
third phase occurred after the development of renal
tubular dysfunction, which was manifested by
increased urinary excretion of cadmium and
decreased concentration of cadmium in the kidney.
During this phase, cadmium concentrations in urine
were high and were no longer an indicator of the
current exposure.
Factors Affecting Interpretation
of Measurements
Analytical Procedure and Sampling
The results of analysis depend on the method.
Contamination of reagents and loss of cadmium due
to volatilization during analysis are major sources of
error. Implementation of analytical quality assurance
programs is recommended. Creatinine measurement
is required.
Exposure
Nonoccupational exposure to cadmium, in-
cluding cigarette smoking, makes a minor contribu-
tion to cadmium concentrations in urine of exposed
workers. Cadmium concentrations above 5 µg/g of
creatinine may be a result of either long-term accum-
ulation of cadmium or a very high recent exposure,
or of both. It may take more than a year of occupa-
tional exposure to increase the body burden to the
extent that cadmium excretion rises above back-
(20–25)
ground levels.
Population
Renal tubular dysfunction of any etiology may
result in increased urinary excretion of cadmium.
Renal tubular function tests should be performed in
all workers with an elevated cadmium concentration
in urine. Measurements of cadmium in urine speci-
mens obtained from workers with evidence of renal
tubular dysfunction should not be used for evalua-
tion of workplace exposure.
Justification
The previous BEI of 10 µg/g of creatinine,
recommended in 1985, was intended to protect
against renal dysfunction in nearly all workers.
Studies available at that time indicated a low
ACGIH  2001

incidence of renal dysfunction in workers with
cadmium concentrations in urine below 10 µg/g of
creatinine. Moreover, the clinical significance of low-
molecular-weight proteinuria was uncertain.
Relationship Between Cadmium Concentration
in Urine and Renal Function
A number of recently published studies indicate
an increased excretion of markers of renal dysfunc-
tion in workers with cadmium concentrations in urine
between 5 and 10 µg/g of creatinine. The most
commonly studied markers are the low-molecular-
mass proteins, β2-microglobulin (β2M), retinol binding
protein (RBP), and a lysosomal enzyme N-acetyl-β-
D-glucosaminidase (NAG). Alkaline phosphatase
(AP), alanine aminopeptidase (AAP) and γ-glutamyl-
transferase (GGT) have been examined less fre-
quently.
(26,27)
In the absence of a reduced glomerular
filtration rate, increased urinary excretion of β2M is
considered to be a sign of a proximal tubular defect,
which will likely be followed by a progressive loss of
renal parenchyma if exposure to cadmium contin-
(28)
ues. NAG exists as two isoenzymes. Increased
excretion of NAG may represent either functional
enzymuria from accumulation of cadmium (isoen-
zyme A) or lesional enzymuria from damage to
(29)
tubular cells (isoenzyme B). Usually, only total
NAG is measured. For more information, see the
reviews of clinical tests for early detection of renal
dysfunction.
(30,31)
Recent studies of the relationships between
cadmium concentrations in urine and blood and the
excretion of renal tubular function markers are sum-
marized in Table 1. Most studies were a cross sec-
tion of a small number of workers. Definition of
normal renal function and dysfunction varied. The
gender of the workers also varied and often was not
specified. Data were not always analyzed to deter-
mine thresholds for renal effects and long-term fol-
low-up of affected workers was limited. The studies
are reviewed below.
(32)
Elinder et al. examined workers five years
after cessation of exposure to cadmium solder. In
workers excreting cadmium of 5 to 10 µg/g of
creatinine, the incidences of "mild" and "marked"
β2M-uria were 33% and 11%, respectively. In work-
ers excreting cadmium above 10 µg/g of creatinine,
the incidences were 80% (mild) and 60% (marked).
(33)
Liu et al. found tubular dysfunction in 13.8% of
cadmium smelter workers with an average cadmium
concen-tration of 5 µg/g of creatinine (determined
using a voltametric method). The cadmium concen-
tration in urine of nine workers with tubular dysfunc-
tion ranged between 4.9 and 13.5 µg/g of creatinine.
(34)
Smith et al. reported a 38% incidence of mild
β2M-uria in solderers excreting more than 10 µg/g of
creatinine and a 10% incidence in those who ex-
creted less than 10 µg/g of creatinine. A follow-up
study of 19 workers showed decreasing cadmium
excretion but unchanged renal function. Jakubowski
2001 © ACGIH
et al. found that β2M and RBP were elevated in
(35)
about 10% of alkaline battery factory workers ex-
creting cadmium in concentration between 10 and
(36)
15 µg/g of creatinine. Shaikh et al. pooled cad-
mium smelter workers into four groups according to
length of employment. Two groups with a mean
cadmium excretion above 14 µg/g of creatinine
excreted significantly more beta-2-M than the two
groups with mean cadmium concentrations of 3.0
and 5.8 µg/g of creatinine, respectively.
(37)
Verschoor et al. compared men exposed to
cadmium at a pigment plant (n = 19) and in radiator
welding (n = 7) to controls (n = 8). Workers were
divided into three groups: group 1 — urine cadmium
< 3 µg/g of creatinine (n = 22); group 2 — urine
cadmium between 3 and 5 µg/g of creatinine (n = 7);
and group 3 — urine cadmium > 5 µg/g creatinine (n
= 5). β2M excretion was increased in all three
groups. NAG excretion was increased only in group
3. Cadmium concentration in urine correlated better
with beta-2-M concentration than with NAG concen-
tration. Urine protein electrophoresis showed that
workers with cadmium concentrations above 5 µg/g
of creatinine excreted more low-molecular-mass
proteins and less high-molecular-mass proteins than
controls and workers with cadmium concentrations
(38)
below 5 µg/g of creatinine. Christoffersson et al.
observed that nickel cadmium battery workers
(mean cadmium concentration in urine 5.4 µg/g of
creatinine) excreted more β2M in urine than controls
(mean cadmium concentration of 0.8 µg/g of creat-
inine). The increase was statistically significant, but
the measured values did not exceed the normal
levels of β2M.
(39)
Mason et al. compared 75 male copper
cadmium alloy workers (mean cadmium concentra-
tion 7.1 µg/g of creatinine, almost all below 10 µg/g)
with 75 matched controls (mean cadmium concen-
tration 0.8 µg/g of creatinine). The urinary excretion
of β2M, RBP, NAG, AP, GGT, total protein, and
albumin was significantly higher in exposed workers
(40)
than in controls. Mueller et al. examined the
dose–response relationships between urinary
concentrations of cadmium, NAG and AAP in cad-
mium smelter workers. NAG and AAP concentra-
tions in urine were significantly higher in workers
with urinary cadmium concentrations above 2 µg/L
than in those with concentrations below 2 µg/L.
Probit analyses indicated that 10% of NAG values
were elevated in urine of workers excreting cadmium
at 6.3 µg/g of creatinine, while 10% of AAP values
were elevated in urine of workers excreting cadmium
at 5 µg/g of creatinine.
(41)
Kawada et al. studied workers (sex unre-
ported) exposed to relatively low levels of cadmium
pigment dust. Cadmium concentrations in urine were
below 10 µg/g of creatinine (geometric mean 1.2
µg/g of creatinine). Cadmium concentration in urine
correlated better with NAG excretion than with β2M
excretion. The data do not indicate a threshold, but
Cadmium & Compounds BEI – 3
TABLE 1. Studies of Relationships Between Cadmium in Urine and Blood and â2M and NAG in Urine
Avg. Urine Blood Urine NAGC
B
Exposure Age CadmiumC CadmiumC Urine â2M C
(ì /g creat.
Author N SexA (yrs) (yrs) (ì g/g creat.) (ì g/L) (ì g/g creatinine) or other)
Elinder 60 58 M >5 48 2 1/14 > 300
(1985)(32) 2–5 3/12 > 300
(0/12 > 900)
5–10 6/18 > 300
(2/18 > 900)
10–15 4/5 > 300
(3/5 > 900)
Liu 65 47 M 7.8 35.3 5.03 (0.9–42.6) 20.3 224.1 (8 > 420)
(1985)(33)
Smith 21 ? 0–5 28 < 10 (20/21) < 10 (18/21) 2/21 > 220
(1986)(34) 32 ? >5 42 > 10 (31/32) > 10 (28/32) 12/32 > 220
Jakubowski 85 45 M 0 41 1.0 (0.2–4.6) 4.8 (1.3–18.0) 59 (9–380)
(1987)(35) 102 45 M >5 41 > 10 (57/102) > 10 (66/102) 20% > 380
Shaikh 20 M 1.5 27.2 3.0 (1.9–4.8) 82 (5–122)
(1987)(36) 13 M 11.5 47.6 5.8 (3.2–10.4) 86 (28–263)
13 M 18.6 52 13.3 (7.1–25) 586 (145–2354)
7 M 32.4 56.3 14.0 (9.9–20) 523 (170–1607)
Verschoor 22 M 0 45 <3 0.2 100 (63–155) 41 (Mì /L)
(1987)(37) 7 M 8.7 39 3–5 1.2 172 (88–339) 38
5 M 10.3 41 >5 5.7 258 (97–689) 68
Christoffersson 20 M 5.4 (2.5–13) 125 (29–605)
(1987)(38) 20 M 0.8 59 (13–525)
Mason 75 M >1 55 7.1 (± 1.1) 8.8 (± 0.1) 935 (± 12) 9.8 (IU/g)
(1988)(39) 75 M 0 55 0.8 (± 1.1) 1.4 (± 0.1) 156 (± 10) 6.2
Mueller 36 M 0 48.0 < 2.0 (1 ± 1) 2±2 95% < 3.11
(1989)(40) 40 M ? 56.7 > 2.0 (10 ± 7) 10.2 ± 5.4 15% > 3.11
Kawada 53 ? 0 29.9 0.96 (± 1.68) 0.27 245 2.3
(1990)(42) 9 ? 10.4 30.8 0.87 (± 167) 0.71 249 3.3
8 ? 11.3 33.1 0.86 (± 2.29) 1.21 300 2.7
9 ? 14.6 37.4 2.00 (± 3.40) 2.44 197 4.1
Chia 9 F 0 32.7 0.09 0.79 (± 0.44) 95.2 108.6
(1989)(43) (nmol/h/mg Cr)
65 F 3.7 34.6 1.73 (± 3.0) 7.57 (± 5.89) 213.2 218.4
13 <3 2/13 > 200 6/13 > 139
15 3–5 0/15 9/15 > 139
24 5–10 3/24 15/24 > 139
13 >10 5/13 11/13 > 139
Bernard 58 M 10.4 43.5 6.23 (0.87–165) 6.54 (1.6–51) 107 1.3 (0.46–8.76)
(1990)(44) (11.7–136,000)
58 M 0 43.1 0.66 (0.14–2.5) 0.89 (0.3–2.9) 53.3 (4.7–255) 0.96 (0.18–2.84)
61 41.3 <2 0>300
25 45.2 2–55 0>300
15 44.3 5–10 0>300
15 46 > 10 26% > 300
A
M = male; F = female.
B
Average (number) or minimum (<).
C
Average (range) or category.

rather a continuous response of NAG excretion to
increasing cadmium concentrations. This finding was
confirmed in a follow-up study of the same work-
(42) (43)
ers. Chia et al. reported similar results in
female nickel cadmium battery workers. NAG con-
centrations rose continuously with the cadmium
concentration in urine, the increase becoming
statistically significant when cadmium excretion
exceeded 3 µg/g of creatinine. Urinary excretion of
β2M also rose with increasing cadmium concen-

4 – Cadmium & Compounds BEI ACGIH  2001

trations in urine, but the correlation was insignificant.
(44)
Bernard et al. studied 58 cadmium smelter
workers (mean cadmium concentrations 6.23 µg/g)
and 58 matched control workers (mean cadmium
concentration 0.66 µg/g). Mean concentrations of
β2M and NAG, but not RBP, in urine were signifi-
cantly increased in the exposed group compared to
controls. The prevalences of increased concentra-
tions of β2M, NAG, RBP, and protein 1 (an α-micro-
globulin of molecular weight 20,000) were higher in
cadmium workers than in controls. The difference
was, however, statistically insignificant. When the
data were grouped according to cadmium excretion,
the prevalences of increased values for the four
tubular markers were increased only if cadmium
excretion exceeded 10 µg/g of creatinine. Urinary
albumin and transferrin, markers of glomerular
dysfunction, were increased in some workers with
cadmium excretion below 10 µg/g of creatinine. The
authors concluded that subtle defects in glomerular
function in some cadmium-exposed subjects may
precede the onset of tubular impairment.
(45)
Ishizaki et al. compared urinary excretion of
cadmium and β2M in 3178 individuals in the 50-plus
age group residing in cadmium-polluted areas and
294 residents of similar age in nonpolluted areas.
Probit regression lines determined that the cadmium
threshold for increasing β2M-uria is between 3.8 and
4.0 µg/g of creatinine for men and between 3.8 and
4.1 µg/g of creatinine for women.
Significance of Low-Molecular-Weight Proteinuria
(46)
Roels et al. conducted a follow-up study of 23
workers removed from cadmium exposure for at
least 5 years because of increased excretion of low-
molecular-mass proteins. Proteinuria persisted, as
did an increase in serum creatinine and progressive
decrease in glomerular filtration rate (average 31
2
ml/min/1.73 m , which is five times that accounted
for by aging). The authors concluded that early, sub-
clinical renal changes should be regarded as an
adverse effect, predictive of exacerbation of the age-
related decline in glomerular filtration rate. Huang
(47)
and Liu followed up 17 workers removed from
cadmium exposure for 0.5 to 3.7 years. During the
2.5-year follow-up period, the mean β2M concentra-
tion more than doubled, and five workers with
normal β2M values at time of removal developed
abnormal values.
Relationship Between Cadmium Excretion
and Lung Function
(48)
Edling et al. used spirometry to assess the
lung function of 57 male workers previously exposed
to cadmium solder. There were no differences from
controls in spite of the fact that 24 workers (42%)
had β2M-uria. Davison et al. compared carbon
(49)
monoxide transfer coefficient factors and chest
radiographs of 101 male copper cadmium alloy
workers to matched controls; they reported evidence
2001 © ACGIH
of emphysema in workers after five or more years of
exposure to cadmium.
Relationship Between Cadmium Excretion and
Lung Cancer
(50)
Thun et al. updated the cohort study on
mortality among U.S. cadmium production workers
with an increased risk for lung cancer. (This study
was one of the bases for lowering the TLV–TWA for
cadmium.) Cadmium concentration in urine has
been measured periodically since 1948, but on an
average, only two samples were taken per person
(range 0 to 79). The measurements indicate a high
exposure: in 90% of the measurements, median
cadmium concentration was above 10 µg/L, and in
81%, it was above 20 µg/L. This study is not suitable
for determination of a threshold for lung cancer
because the majority of workers rapidly achieved
cadmium concentrations above 10 µg/g of
creatinine.
Summary
Most studies indicated an increase of either
NAG or β2M excretion when the cadmium excretion
exceeded 5 µg/g of creatinine. Although these
changes were subclinical and often within the range
of normal values, there was evidence that they may
have been followed by deterioration of renal
function, which may have persisted after cessation
of exposure. Although this effect of cadmium on the
kidney may not be pathological, the data suggested
that the changes might progress and become
clinically significant when combined with effects
associated with aging. Therefore, it is prudent to
maintain cadmium concentration in urine below 5
µg/g of creatinine.
There is no evidence for adjusting the cadmium
(51,52)
concentration for urine density.
Current Database Available
The amount of information on the relationship
between cadmium concentration in urine and renal
function is adequate to support the BEI.
Recommendation
®
ACGIH recommends monitoring of cadmium in
urine as a specific test for chronic exposure to
cadmium. Cadmium concentration of 5 µg/g of
creatinine is recommended as a BEI. Sampling time
is not critical, but precautions must be taken to avoid
contamination. The BEI is intended to prevent the
potential for renal dysfunction in workers. The BEI of
5 µg/g of creatinine is supported by studies
indicating altered excretion of markers of renal
dysfunction at cadmium excretion above 5 µg/g of
creatinine.
The recommended BEI is equivalent in
International System of Units (SI) to 5 µmol/mol of
creatinine.
Cadmium & Compounds BEI – 5
 CADMIUM IN BLOOD
Analytical Methods
The most widely used method for determination
of cadmium in blood is atomic absorption spectro-
photometry (AAS) with an electrothermal atomization
(4,9,10)
detector (ETA). Procedures for preparation of
quality control samples of bovine blood spiked with
cadmium nitrate and reference analysis by isotope
(17)
dilution mass spectrometry has been described.
Although no certified reference standards are
available, freeze-dried blood reference samples are
commercially available in Germany.
(10,16)
Sampling and Storage
Samples should be collected in acid-cleaned
heparinized glass or plastic tubes free from heavy
(10)
metal contamination. Samples should be
analyzed on the same day as collected or kept
refrigerated if analyzed on the next day.
Biological Levels
Without Occupational Exposure
Cadmium concentrations in blood increase with
age, cigarette smoking, and intake from environ-
(19) (19)
mental pollution. Elinder reviewed a number of
studies measuring cadmium concentration in blood
of nonoccupationally exposed persons and con-
cluded that, in countries where dietary intake is
between 10 and 20 µg/day, nonsmokers have a
median cadmium concentration in blood between
0.4 and 1.0 µg/L, and smokers have median concen-
tration between 1.4 and 4.5 µg/L. The influence of
sex and age on cadmium concentration in blood
appears to be overshadowed by the impact of
smoking. There is a dose-related increase in
cadmium concentration in blood and number of
cigarettes smoked per day.
Kinetics
At least 70% to 80% of the cadmium in blood is
present in erythrocytes, from which approximately
(2–4)
60% is bound to metallothionein. Cadmium in
plasma is bound to at least two different proteins,
probably metallothionein and albumin.
Two studies have examined the rise in cadmium
concentration in blood during occupational expo-
sure. In the blood of four new employees exposed to
3 (25)
110 at 2125 µg Cd/m , Lauwerys et al. observed a
linear increase of cadmium concentration up to 120
days of exposure, followed by a plateau. A similar
(24)
observation was made by Kjellstrom in 17 new
employees exposed at a cadmium concentration of
3
50 µg/m .
(53)
Jarup et al. studied five workers for 15 years
after cessation of cadmium exposure. The elimina-
tion was biphasic with half-lives of 75 to 130 days
6 – Cadmium & Compounds BEI
and 7.4 to 16 years (11–16 years without renal
dysfunction).
Factors Affecting Interpretation
of Measurements
Analytical Procedure and Sampling
The results of analysis depend on the analytical
method. Contamination of reagents and loss of
cadmium due to volatilization during analysis are
major sources of error. Analytical quality assurance
programs should be implemented.
Exposure
The contribution of tobacco smoking to cadmium
concentrations in blood may be significant, particu-
larly at low occupational exposure when the cadmi-
um concentration in blood is below 5 µg/L. Cadmium
concentration in blood is partly related to body
burden, partly to the recent exposure. Regular
monitoring of cadmium in blood was suggested for
(53–57)
the estimation of cumulative dose of cadmium.
Population
No population characteristics influencing cad-
mium concentrations in blood have been identified.
Justification
The previously recommended BEI of 10 µg/L for
cadmium in blood was based on a number of studies
suggesting a low incidence of renal dysfunction in
workers whose cadmium concentration in blood
(25–27,55,58,59)
consistently remained below 10 µg/L. In
one study of subacute intoxication in jewelry
workers, an estimated threshold concentration of
(57)
cadmium in blood was between 5 and 10 µg/L.
However, these studies were not conclusive.
Relationship Between Cadmium Concentration
in Blood and Renal Function
Several studies indicated higher incidence of
renal dysfunction in workers with cumulative cadmi-
um concentration in blood below 10 µg/L than previ-
ously estimated (Table 1). Dose–response relation-
(35)
ship reported by Jakubowski et al. indicates an
increase of low-molecular-mass protein excretion in
about 10% of workers having cadmium concentra-
tion in blood equal to 10 µg/L for 30 to 40 years.
(39)
Mason et al. observed changes in markers of
renal function (urinary β2M, RBP, NAG, AP, GGT,
total protein, and albumin) in workers with a mean
cadmium concentration in blood equal to 8.8 µg/L
(43)
(mostly below 10 µg/L). Chia et al. studied female
workers exposed to cadmium. Mean urinary NAG
excretion started to rise when cadmium in blood
reached a concentration of 1 µg/L, leveled off at
cadmium concentrations between 3 and 10 µg/L,
and then rose sharply. β2M did not start to rise until
cadmium concentrations in blood exceeded 10 µg/L.
ACGIH  2001
 (44)
Bernard et al. reported the absence of tubular
effects and the presence of subtle glomerular
dysfunction (increased albumin excretion measured
by a very sensitive assay) in workers with a
cadmium concentration below 10 µg/L.
(56)
Jarup et al. examined 440 workers (326 men
and 114 women) exposed to cadmium oxide dust in
battery manufacturing. Cumulative cadmium concen-
trations in blood were calculated from an average of
seven measurements per worker taken over 15
years. The measure of tubular proteinuria was β2M
excretion exceeding a concentration of 35 µg/mmol
(311 µg/g) of creatinine. A dose–response
relationship between the prevalence of tubular pro-
teinuria and cumulative cadmium concentration in
blood predicted that the 5%, 10%, and 16% preval-
ence of tubular proteinuria appeared at concentra-
tions of 2.8, 5.6, and 10 µg/L, respectively. This thor-
ough study indicates that the prevalence of tubular
proteinuria may become significant even if cadmium
concentrations in blood remain for many years at 5
µg/L. Although the observed changes were subclini-
cal, there is evidence that they persist and may be
followed by deterioration of renal function, even after
the cessation of the exposure. Therefore, it is
prudent to maintain an average cadmium
concentration in blood below 5 µg/L.
Current Database Available
The information on blood cadmium is scant
compared with the information available on urinary
cadmium. It is, nevertheless, adequate to
recommend a BEI of 5 µg/L.
Recommendation
reflect chronic exposure. The BEI is intended to pre-
vent the potential for renal dysfunction in workers.
The BEI of 5 µg/L is supported by recent studies
indicating altered excretion of markers of renal
dysfunction at concentrations below 10 µg/L.
The recommended BEI is equivalent in SI units
to 0.044 µmol/L.
Other Reference Values
(60)
The World Health Organization in 1980 recom-
mended that cadmium concentrations should not be al-
lowed to exceed 10 µg/g of creatinine or 10 µg/L of
blood. Control measures should be applied if a measure-
ment exceeds 5 µg/g of creatinine or 5 µg/L of blood.
In 1990, the U.S. Occupational Safety and Health
Administration proposed annual monitoring of cadmium
in blood and urine and of protein in urine of all workers
(61)
exposed to cadmium. When cadmium concentrations
exceeded 5 µg/g of creatinine, exposure and work
practices should be reassessed and appropriate
measures taken to reduce the exposure.
The German Commission for the Investigation of
Health Hazards of Chemical Compounds in the Work
Area recommends the following Biological Tolerance
(54)
Values (BATs): 15 µg Cd/L blood and 15 µg Cd/L
urine. These BAT values are strictly for nephrotoxic
effects.
Other Indicators of Exposure
Metallothionein in urine appears to correlate with
cadmium concentration in urine, offering the
advantage of a specific assay without interference
by contamination. Reviews of a metallothionein test
revealed that the data were inadequate to
recommend a BEI.
(62–66)

ACGIH recommends monitoring of cadmium in
blood as a specific indicator of the recent exposure
to cadmium. Cadmium concentration of 5 µg/L is
recommended as a BEI for the monitoring of
cadmium exposure. The sampling time is discretion-
ary. Precautions must be taken to avoid contamin-
ation. Cadmium concentration in blood primarily
reflects recent exposure and is complementary to
the cadmium measurements in urine, which primarily
Cadmium in liver and kidney can be determined
(67,68)
in vivo by neutron activation analysis (NAA). A
(69)
transportable unit has been developed. Due to
limitations in the availability of equipment, the BEI
Committee does not recommend monitoring
cadmium in liver or kidney.
The BEI Committee does not recommend
monitoring for cadmium in hair because the
concentration correlates poorly with body burden,

Historical BEIs
Date Action Determinant Sampling Time BEI Notation
1986 Proposed Cadmium in urine Not critical 10 µg/g creatinine †
Cadmium in blood Not critical 10 µg/L †
1987 Proposed Cadmium in urine Not critical 10 µg/g creatinine B
Cadmium in blood Not critical 10 µg/L B
1988 Adopted Cadmium in urine Not critical 10 µg/g creatinine B
Cadmium in blood Not critical 10 µg/L B
1991 Proposed Cadmium in urine Not critical 5 µg/g creatinine B
Cadmium in blood Not critical 5 µg/L B
1993 Adopted Cadmium in urine Not critical 5 µg/g creatinine B
Cadmium in blood Not critical 5 µg/L B

2001 © ACGIH Cadmium & Compounds BEI – 7

and distinction between endogenous and exogenous
(2–4,26,70)
cadmium is not always possible.
A number of tests indicating effects of cadmium
on organ function are included in a complete pro-
ram of medical monitoring. Tests for renal function
include β2M, RBP, NAG. AP, AAP, GGT, total
protein, albumin, protein electrophoresis, amino
acids, glucose, and clearance of creatinine, calcium,
and phosphate. Tests for lung function include
pulmonary function tests, chest X-rays, and diffusing
capacity measurements. These tests relate to health
effects of cadmium rather than to cadmium
exposure; therefore, these determinants are not
recommended.
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2001 © ACGIH
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ACGIH  2001