Table 3-8Benchmark Dose Estimations of Urinary Cadmium Levels (µg/g Creatinine)

Study
population
Effect
biomarker
Response
criterion
BMD
model
5% BMR10% BMRReference
BMDBMDLBMDBMDL
General population (Sweden)
790 females; 53–64 years old
NAG3.6 U/g creat.
(95% cut-off)a
Profile likelihood method0.640.501.080.83Suwazono et al. 2006
pHC6.8 mg/g creat.
(95% cut-off)a
0.630.491.050.81
Estimated GFR78.5 mL/minute
(95% cut-off)a
1.080.701.801.18
Residents in cadmium-polluted
(1,397 males, 1,706 females) and cadmium nonpolluted areas (Japan) (130 males, 159 females); ≥50 years old
β2M507 µg/g creat. (M)Quantal linear model1.5 (M)1.2 (M)3.1 (M)2.5 (M)Shimizu et al. 2006
400 µg/g creat. (F)
(84% cut-off)b
1.4 (F)1.1 (F)2.9 (F)2.3 (F)
507 µg/g creat. (M)Log-logistic model3.7 (M)2.9 (M)5.1 (M)4.2 (M)
400 µg/g creat. (F)
(84% cut-off)b
2.6 (F)1.5 (F)6.3 (F)2.7 (F)
994 µg/g creat. (M)Quantal linear model2.3 (M)1.8 (M)4.7 (M)3.7 (M)
784 µg/g creat. (F)
(95% cut-off)c
1.7 (F)1.4 (F)3.5 (F)2.9 (F)
994 µg/g creat. (M)Log-logistic model4.8 (M)3.9 (M)6.3 (M)5.5 (M)
784 µg/g creat. (F)
(95% cut-off)c
4.4 (F)3.2 (F)6.4 (F)5.1 (F)
Residents in cadmium-polluted
(1,397 males, 1,706 females)d and cadmium nonpolluted areas (Japan)
(520 males, 700 females); ≥50 years old
β2M915.5 µg/g creat. (M)Profile likelihood method4.0 (M)3.5 (M)Suwazono et al. 2011b
897.1 µg/g creat.
(95% cut-off)e
4.0 (F)(3.7)F)
General population (Japan)
1,114 males, 1,664 females
Protein157 mg/g creat. (M)Log-logistic model3.6 (M)3.1 (M)5.6 (M)4.9 (M)Kobayashi et al. 2006
159 mg/g creat. (F)
(84% cut-off)f
4.8 (F)4.2 (F)7.5 (F)6.6 (F)
309 mg/g creat. (M)10.6 (M)6.8 (M)15.3 (M)9.6 (M)
311 mg/g creat. (F)
(95% cut-off)g
8.7 (F)7.3 (F)12.0 (F)9.9 (F)
β2M507 µg/g creat. (M)2.9 (M)2.4 (M)5.0 (M)4.0 (M)
400 µg/g creat. (F)
(84% cut-off)f
3.8 (F)3.3 (F)6.6 (F)5.5 (F)
994 µg/g creat. (M)6.4 (M)4.5 (M)10.2 (M)7.1 (M)
784 µg/g creat. (F)
(95% cut-off)g
8.7 (F)7.3 (F)12.0 (F)9.9 (F)
NAG8.2 U/g creat. (M)4.8 (M)3.3 (M)8.3 (M)5.7 (M)
8.5 U/g creat. (F)
(84% cut-off)f
4.7 (F)3.7 (F)8.3 (F)6.4 (F)
16.0 U/g creat. (M)12.0 (M)7.7 (M)16.4 (M)10.3 (M)
16.6 U/g creat. (F)
(95% cut-off)g
10.8 (F)8.5 (F)14.8 (F)11.4 (F)
General population (Japan)
1,181 males, 1,748 females
β2M492 µg/g creat. (M)Multiple logistic model3.0 (M)2.7 (M)5.0 (M)4.6 (M)Kobayashi et al. 2008a
407 µg/g creat. (F)
(84% cut-off)h
3.4 (F)3.2 (F)5.7 (F)5.4 (F)
965 µg/g creat. (M)4.9 (M)4.5 (M)7.4 (M)6.8 (M)
798 µg/g creat. (F)
(97.5% cut-off)i
5.9 (F)5.6 (F)8.6 (F)8.1 (F)
1,000 µg/g creat.5.0 (M)4.6 (M)7.5 (M)6.9 (M)
6.7 (F)6.3 (F)9.4 (F)8.9 (F)
General population (Japan)
547 males, 723 females; aged ≥50 years
Protein159 mg/g creat. (M)Profile likelihood method2.6 (M)2.1 (M)Suwazono et al. 2011c
93 mg/g creat. (F)
(95% cut-off)a
1.7 (F)1.5 (M)
β2M708 µg/g creat. (M)3.4 (M)2.6 (M)
415 µg/g creat. (F)
(95% cut-off)e
1.7 (F)1.4 (F)
NAG10.7 IU/g creat. (M)6.3 (M)4.1 (M)
11.1 IU/g creat. (F)
(95% cut-off)j
4.3 (F)3.1 (F)
General population (Japan)
410 males, 418 females; 40–59 years old
Protein70 mg/g creat. (M)Quantal linear model0.9 (M)0.6 (M)1.9 (M)1.2 (M)Uno et al. 2005
70 mg/g creat. (F)
(84% cut-off)k
3.2 (F)1.8 (F)6.6 (F)3.6 (F)
β2M233 µg/g creat. (M)0.5 (M)0.4 (M)1.0 (M)0.7 (M)
274 µg/g creat. (F)
(84% cut-off)k
0.9 (F)0.8 (F)1.8 (F)1.3 (F)
NAG2.4 U/g creat. (M)0.3 (M)0.3 (M)0.7 (M)0.6 (M)
2.5 U/g creat. (F)
(84% cut-off)k
0.8 (F)0.6 (F)1.6 (F)1.2 (F)
General population (Japan)l
209 males, 215 females; 40–49 years old
Protein67.7 mg/g creat. (M)Profile likelihood method1.3 (M)0.9 (M)Suwazono et al. 2011a
94.6 mg/g creat. (F)
(95% cut-off)a
3.2 (F)1.9 (F)
β2M224.5 µg/g creat. (M)0.9 (M)0.7 (M)
298.9 µg/g creat. (F)
(95% cut-off)a
2.2 (F)1.5 (F)
NAG2.2 IU/g creat. (M)0.7 (M)0.6 (M)
2.1 IU/g creat. (F)
(95% cut-off)
1.3 (F)0.6 (F)
General population (Japan)j
201 males, 203 females; 50–59 years
Protein94.5 mg/g creat. (M)Profile likelihood method1.6 (M)1.1 (M)Suwazono et al. 2011a
92.7 mg/g creat. (F)
(95% cut-off)a
5.7 (F)3.4 (F)
β2M322.1 µg/g creat. (M)1.8 (M)1.2 (M)
296.7 µg/g creat. (F)
(95% cut-off)a
2.4 (F)1.8 (F)
NAG2.5 IU/g creat. (M)1.0 (M)0.8 (M)
3.3 IU/g creat. (F)
(95% cut-off)a
3.2 (F)2.3 (F)
Residents in cadmium highly polluted area (China)
123 males, 171 females
NAG15.0 U/g creat.
(95% cut-off)m
Quantal linear logistic regression model6.36 (M)5.83 (M)Jin et al. 2004c
7.74 (F)5.46 (F)
NAG-B4.0 U/g creat.
(95% cut-off)k
4.88 (M)3.98 (M)
4.24 (F)3.70 (F)
β2M800 µg/g creat.
(95% cut-off) m
5.86 (M)4.74 (M)
9.98 (F)8.47 (F)
Residents in cadmium moderately polluted area (China)
81 males, 162 females
RBP0.300 mg/g creat.
(95% cut-off)m
5.99 (M)4.87 (M)
9.03 (F)7.63 (F)
Albumin25.0 mg/g creat.
(95% cut-off)m
16.72 (M)11.18 (M)
14.42 (F)11.31 (F)
a

95th percentile of effect biomarkers on the “hypothetical” control distribution at a urinary cadmium level of zero.

b

84% upper limit values from a group of 424 males and 1,611 females who did not smoke and lived in three different cadmium nonpolluted areas.

c

95% upper limit values from a group of 424 males and 1,611 females who did not smoke and lived in three different cadmium nonpolluted areas.

d

Same population of residents living in polluted area as Shimizu et al. (2006).

e

95th percentile calculated by benchmark model at no cadmium exposure (urinary cadmium equal to zero), adjusted to mean age.

f

84% upper limit value of the target population of people who have not smoked.

g

95% upper limit value of the target population of people who have not smoked.

h

84th percentile level in subjects from nonpolluted areas.

i

97.5th percentile level in subjects from nonpoulluted areas.

j

95th percentile calculated by benchmark model at no cadmium exposure (urinary cadmium equal to zero), adjusted to mean age in females only.

k

84% upper limit value of the target population.

l

Same population as Uno et al. (2005), divided into two age groups.

m

95% upper limit value from a control group 98 males and 155 females living in a cadmium nonpolluted area.

BMD = benchmark dose; BMDL = lower 95% confidence limit on the benchmark dose; BMR = benchmark response; β2M = β2-microglobulin; creat. = creatinine; F = female; M = male; NAG = N-acetyl-β-D-glucosaminidase; NAG-B = N-acetyl-β-D-glucosaminidase’s isoform B; RBP = retinol binding protein

From: 3, HEALTH EFFECTS

Cover of Toxicological Profile for Cadmium
Toxicological Profile for Cadmium.
Faroon O, Ashizawa A, Wright S, et al.

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