efsa-opinion-chromium-food-drinking-water

Chromium in food and bottled water
Table J13: Chronic inflammation of the liver in female rats. The benchmark dose (BMD 10 ) and the
95 % benchmark dose lower confidence limit (BMDL 10 ) values are given for a BMR of 10 % extra risk
with characteristics of the model fit. The model with lowest BMDL 10 is highlighted in bold.
Data Dose 0 0.24 0.94 2.4 7.0
Response 12/50 21/50 28/50 35/50 39/50
Models
Restriction
N of
parameters
Minus
Loglikelihood
P-
value
Accepted
BMD 10
(mg/kg
b.w. per
day)
Full model na 5 152.7 – – – –
Null (reduced) model na 1 172.5 - - - -
BMDL 10
(mg/kg
b.w. per
day)
Probit na 2 158.9 0.006 no 0.88 0.70
LogProbit none 3 1.52.9 0.91 yes 0.052 0.0031
Logistic na 2 1.58.7 0.008 no 0.84 0.65
LogLogistic none 3 1.52.8 0.92 yes 0.043 0.0021
Quantal-Linear (QL) na 2 157.0 0.04 no 0.51 0.37
Multistage Cancer na 1 157.0 0.04 no 0.52 0.37
Multistage none 3 153.4 0.51 yes 0.20 0.14
Weibull none 2 153.0 0.82 yes 0.021 0.0005
Gamma none 2 153.1 0.72 yes 0.0096 0.00005
b.w.: body weight; na: not applicable; if: invalid fit.
Multistage Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL
Weibull Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL
0.9
Multistage
BMD Lower Bound
0.9
Weibull
BMD Lower Bound
0.8
0.8
0.7
0.7
Fraction Affected
0.6
0.5
0.4
Fraction Affected
0.6
0.5
0.4
0.3
0.3
0.2
0.2
0.1
09:17 01/21 2014
BMDL BMD
0 1 2 3 4 5 6 7
dose
0.1
BMDLBMD
0 1 2 3 4 5 6 7
dose
09:15 01/21 2014
Figure J13: Fits of the Multistage model (left) and Weibull model (right) to the dose-response data on
chronic liver inflammation in female rats.
J 2.2.
Diffuse epithelial hyperplasia in the duodenum in male mice
For the dose-response analysis of the incidence of diffuse epithelial hyperplasia in the duodenum in
male mice only one non-restricted model (multistage) showed an acceptable fit (p > 0.05) which
resulted in a BMDL 10 = 0.11 mg/kg b.w. per day . Using a different modelling approach, not following
EFSA (2009), ADTSR reported a BMDL 10 of 0.13 mg/kg b.w. per day. Two graphs in Figure J14 show
the fit of the unrestricted Multistage model and Weibull model.
EFSA Journal 2014;12(3):3595 244