efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
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Chromium in <strong>food</strong> and <strong>drinking</strong> <strong>water</strong><br />
As recommended for substances which are both genotoxic and carcinogenic, the CONTAM Panel<br />
adopted a margin of exposure (MOE) approach for the risk characterisation of neoplastic effects of<br />
Cr(VI). To this end, lower 95 % confidence limit for a benchmark response of 10 % extra risk<br />
(BMDL 10 ) values were derived from the 2-year carcinogenicity study of the NTP investigating oral<br />
intake of Cr(VI) (as sodium dichromate dihydrate) via <strong>drinking</strong> <strong>water</strong> in male and female rats and<br />
mice. In this study increased incidence of tumours of the squamous epithelium of the oral cavity and<br />
of epithelial tissues of the small intestine was reported in male and female rats and mice, respectively.<br />
In a conservative approach, the CONTAM Panel selected a lowest BMDL 10 of 1.0 mg Cr(VI)/kg b.w.<br />
per day for combined adenomas and carcinomas of the small intestine in male and female mice as<br />
reference point (RP) for estimation of MOEs for neoplastic effects.<br />
The EFSA Scientific Committee has concluded that for substances that are both genotoxic and<br />
carcinogenic, an MOE of 10 000 or higher, based on a BMDL 10 from an animal study, is of low<br />
concern from a public health point of view.<br />
The MOEs calculated for all age groups on the basis of the mean chronic exposure to Cr(VI) via<br />
consumption of <strong>drinking</strong> <strong>water</strong> indicated a low concern (MOE values > 10 000) for all age groups with<br />
the exception of infants at UB exposure estimates (maximum UB - minimum LB, 6 300 - 71 000).<br />
When considering the 95 th percentile exposure, MOE values below 10 000 were found at UB exposure<br />
estimates, particularly for ‘Infants’ (maximum UB - minimum LB, 3 100 - 21 000), ‘Toddlers’<br />
(maximum UB - minimum LB, 4 200 - 62 000), and ‘Other children’ (maximum UB - minimum LB,<br />
6 600 - 360 000).<br />
Similarly to the risk characterization carried out for all types of <strong>drinking</strong> <strong>water</strong>, in the case of exposure<br />
to Cr(VI) through the consumption of bottled <strong>water</strong> MOEs values below 10 000 were mainly found at<br />
UB estimates when considering the 95 th percentile exposure in the youngest populations (‘Infants’,<br />
‘Toddlers’ and ‘Other children’).<br />
The CONTAM Panel noted that the MOE values calculated for exposure to Cr(VI) via consumption of<br />
all types of <strong>drinking</strong> <strong>water</strong>, as well as only bottled <strong>water</strong> were highly influenced by the high proportion<br />
of left-censored data. In addition, when interpreting the numerical values of the MOEs, it should be<br />
considered that they were calculated by using as RP the BMDL 10 for the combined incidence of<br />
adenomas and carcinomas in the mouse small intestine. Because of lack of in vivo data on the capacity<br />
and rate of reduction of Cr(VI) in the rodent and human gastrointestinal tract, there is a significant<br />
uncertainty associated with the use of tumour data in mice to estimate risk at doses of Cr(VI) relevant<br />
for human exposure.<br />
Based on the MOE values for neoplastic effects, the CONTAM Panel concluded that the current levels<br />
of exposure to Cr(VI) via the consumption of all types of <strong>drinking</strong> <strong>water</strong> or of bottled <strong>water</strong> only are of<br />
low concern from a public health point of view for the average consumers but there might be a<br />
potential concern for high consumers particularly in ‘Infants’, ‘Toddlers’ and ‘Other children’.<br />
The inclusion of the <strong>water</strong> used in the preparation of specific <strong>food</strong>s (coffee, tea infusions, and infant<br />
dry and follow-on <strong>food</strong>) led to an increase up to two-fold of the exposure to Cr(VI). However, the<br />
CONTAM Panel was not able to consider this additional contribution to the exposure to Cr(VI) when<br />
deriving MOEs since no reliable data to quantify Cr(VI) in <strong>food</strong> exist.<br />
After repeated oral administration of Cr(VI), in addition to the cancer effects, several toxic effects<br />
were identified in rats and mice including microcytic, hypochromic anaemia, and non-neoplastic<br />
lesions of the liver, duodenum, mesenteric and pancreatic lymph nodes and pancreas. BMD analysis<br />
was performed on the suitable dose-response data for non-neoplastic effects. The BMDL 10 values of<br />
0.27, 0.11 and 0.011 mg Cr(VI)/kg b.w. per day were calculated for non-neoplastic lesions in pancreas<br />
(acinus, cytoplasmic alteration), duodenum (diffuse epithelial hyperplasia) and liver (histiocytic<br />
infiltration), respectively. The Panel noted that the biological significance and cause of histiocytic<br />
cellular infiltration are unknown and therefore it cannot be considered a critical adverse effect. The<br />
BMDL 10 value of 0.11 mg Cr(VI)/kg b.w. per day for diffuse epithelial hyperplasia of the duodenum<br />
in male mice was selected as the RP for the estimation of the MOE for non-neoplastic lesions in the<br />
intestine. In the case of haematological effects a BMDL 05 of 0.2 mg Cr(VI)/kg b.w. per day was<br />
EFSA Journal 2014;12(3):3595 5