efsa-opinion-chromium-food-drinking-water

Chromium in food and bottled water
J 2.7.
Acinus, cytoplasmic alteration in pancreas female mice
For the dose-response analysis of the incidence of acinus,cytoplasmic alteration in pancreas female
mice all non-restricted models, except the probit and logistic model showed an acceptable fit (p > 0.05)
which resulted in BMDL 10 values ranging between 0.72 and 0.26 mg/kg b.w. per day.
The graphs in Figure J19 show the fit of the Gamma and the Weibull model. A BMDL 10 = 0.26 mg/kg
b.w. per day was used to characterize these data.
Using a different modelling approach not following EFSA (2009) ADTSR reported a BMDL 10 of
0.52 mg/kg b.w. per day.
Table J19: Incidence of pancreas acinus cytoplasmic alteration in B6C3D1 female mice exposed to
SDD in drinking water for 2 years. The benchmark dose (BMD -10 ), the 95 % benchmark dose lower
confidence limit (BMDL-10) values for a BMR of 10 % extra risk with characteristics of the model fit.
Data Dose 0 0.38 1.4 3.1 8.7
Response 0/48 6/50 6/49 14/50 32/50
Models
Restriction
BMD
Minus
10 BMDL 10
N of
P-
(mg/kg (mg/kg
Loglikelihood
Accepted
parameters
value
b.w. per b.w. per
day) day)
Full model na 5 99.0 – – – –
Null (reduced) model na 1 134.9 - - - -
Probit na 2 103.6 0.03 no 2.24 1.89
LogProbit none 3 102.2 0.08 yes 0.60 0.30
Logistic na 2 103.9 0.02 no 2.44 2.03
LogLogistic none 3 101.6 0.14 yes 0.64 0.31
Quantal-Linear /QL) na 2 101.4 0.17 yes 0.92 0.72
Multistage Cancer na same as QL
Multistage none 3 101.4 0.08 yes 0.89 0.57
Weibull none 2 100.8 0.25 yes 0.64 0.30
Gamma none 2 100.7 0.30 yes 0.61 0.26
b.w.: body weight; na: not applicable; if: invalid fit.
Weibull Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL
Gamma Multi-Hit Model, with BMR of 10% Extra Risk for the BMD and 0.95 Lower Confidence Limit for the BMDL
0.8
Weibull
BMD Lower Bound
1
Gamma Multi-Hit
BMD Lower Bound
0.7
0.6
0.8
Fraction Affected
0.5
0.4
0.3
Fraction Affected
0.6
0.4
0.2
0.2
0.1
0
0
BMDL
BMD
BMDL BMD
12:33 01/21 2014
0 1 2 3 4 5 6 7 8 9
dose
12:10 01/21 2014
0 1 2 3 4 5 6 7 8 9
dose
Figure J19: Fits of the Weibull model (left) and gamma model (right) to the dose-response data on
acinus, cytoplasmic alteration in pancreas in female mice.
EFSA Journal 2014;12(3):3595 252