efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
and female mice, histiocytic cellular infiltration in the liver in female mice and acinus, cytoplasmic
alteration in pancreas in female mice as the most relevant endpoints for the risk assessment of Cr(VI)
see also ADTSR (2012). A dose response analysis was therefore performed using the default BMR of
10 % extra risk for the incidence of the aforementioned non-neoplastic lesions, and the BMD 10 and its
95 % lower confidence limit BMDL 10 were calculated (see Appendix J.2 for details). The CONTAM
Panel noted that several dose-response data were not suitable for a BMD analysis since the
BMD/BMDL ratios and the range of the BMDL values of the acceptable models were larger than one
order of magnitude such that a BMDL 10 value would either extrapolate orders of magnitude below the
observed dose range or it would depend highly on the model chosen. Therefore no BMDL 10 values for
some of these endpoints could be identified from these data according to guidance given by EFSA
(2009). The BMDL 10 values for endpoints which could be evaluated varied from 0.27 mg Cr(VI)/kg
b.w. per day for acinus, cytoplasmic alterations in pancreas to 0.011 mg Cr(VI)/kg b.w. per day for
histiocytic cellular infiltration in liver in female mice. For male mice the BMD approach was only
applicable to the data of diffuse epithelial hyperplasia in duodenum and resulted in a BMDL 10 of
0.11 mg Cr(VI)/kg b.w. per day (see Table 22).
Table 22: BMD analysis of the data on non-neoplastic effects in the 2-year-studies of the NTP
(2007, 2008) on sodium dichromate dihydrate in male and female F344/N rats and in male and female
B6C3F1 mice. Presence or absence of lesions (i.e. a quantal effect) had been reported in the
publications. For details see Appendix J2.
Effect/
species/sex
liver chronic inflammation
female rats
BMD 10
(mg/kg b.w. per day)
No BMDL could be determined (a)
BMDL 10
(mg/kg b.w. per day)
histiocytic cellular infiltration in liver
female mice 0.067 0.011
diffuse epithelial hyperplasia in duodenum
male mice 0.14 0.11
female mice
No BMDL could be determined (a)
histiocytic cellular infiltration in mesenteric lymph node
male mice
female mice
No BMDL could be determined (a)
No BMDL could be determined (a)
acinus, cytoplasmic alteration in pancreas
female mice 0.61 0.26
(a): No BMDL could be determined since the BMD/BMDL ratios and the range of the BMDL values of the acceptable
models were larger than one order of magnitude such that a BMDL 10 value would either extrapolate orders of magnitude
below the observed dose range or it would depend highly on the model chosen.
Regarding haematological effects the CONTAM Panel noted that several parameters measured in the
2-year NTP study on male rats at day 4, 22, and months 3, 6 and 12 exhibited a statistically significant
change compared to controls and identified the effects on haematocrit, haemoglobin, MCV and MVH
at day 22 after start of treatment with sodium dichromate dihydrate as critical effects, describing the
haematotoxcity of Cr(VI), see also ADTSR (2012). The CONTAM Panel noted that the four data sets
of means and standard errors available for the controls and each of the four dose groups can be
modelled as continuous data. Using the default BMR of 5 %, in the absence of statistical or
toxicological considerations supporting a deviation, the PROAST software was applied and the best
fitting models of the nested Exponential and the Hill family was identified, respectively. The BMD/L
values for the four haematological endpoints are listed in Table 23. The lowest BMDL 05 of 0.2 mg
Cr(VI)/kg b.w. per day was calculated for decreased haematocrit in male rats.
EFSA Journal 2014;12(3):3595 113