Dichromium nitride

Carcinogenicity

Description of key information

Although not being a required endpoint for a registration in the tonnage band 10 -100 tons per year, a review of the existing data on the carcinogenicity of inorganic chromium(III) substances is provided here.

The EFSA concluded in its recent evaluation of chromium in food and drinking water (2014):

"Cr(III) carcinogenicity has been recently addressed by the NTP in their study on Cr picolinate monohydrate (Stout et al., 2009; NTP, 2010) which contains Cr(III) chelated with three molecules of picolinic acid in order to increase the absorption of Cr(III). Chromium picolinate is widely used as dietary supplement. Chromium picolinate monohydrate studies included a 3-month toxicity study to select exposure concentrations for the 2-year studies. These studies are described below.

The study was conducted in 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations from 2000 to 50000 mg/kg for 2 years. A maximal concentration of 50000 mg/kg feed of chromium picolinate monohydrate was selected in order to prevent alteration of the nutritional content of the diet. There were no biologically significant changes in survival, body weight, feed consumption or the occurrence of non-neoplastic lesions in rats or mice in the 2-year studies at concentrations up to 50000 mg/kg feed. This corresponds to average daily doses of 286.2 and 313.7 mg Cr(III)/kg b.w. per day for male and female rats, respectively, and of 783.0 and 727.5 mg Cr(III)/kg b.w. per day for male and female mice, respectively. In male rats, a statistically significant increase in the incidence of preputial gland adenomas at 10000 mg/kg feed (corresponding to 54.9 mg Cr(III)/kg b.w. per day) was reported. However, the incidence of preputial gland hyperplasia was not increased at any exposure dose, neither preputial gland carcinomas were observed in exposed males. There were no increases in the incidence of clitoral gland adenomas or hyperplasia in exposed females (the clitoral gland is the female counterpart of the preputial gland). On the basis of these data the CONTAM Panel concluded that Cr(III) is not carcinogenic in experimental animals."

This conclusion is supported by the also recent ATSDR toxicological profile for chromium (2012) which concluded:

“Chronic-duration studies on oral exposure of humans to chromium(III) compounds were not identified. Several animals studies show no adverse effects associated with chronic-duration oral exposure to chromium(III) compounds (chromium acetate, chromium chloride, chromium nicotinate, chromium oxide, chromium picolinate) (Ivankovic and Preussmann 1975; Mackenzie et al. 1958; Schroeder et al. 1965; Shara et al. 2007), even at very high daily doses. Thus, in the absence of data showing adverse effects of chronic oral exposure, a chronic-duration oral MRL for chromium(III) compounds was not derived.”

The oral carcinogenicity study with chromium(III) picolinate is summarised in the repeated dose toxicity section of the dossier.

These conclusions underline the overall findings in repeated dose toxicity studies, showing no systemic effects (neoplastic or non-neoplastic) after lifetime oral exposure. It is therefore concluded that chromium(III) substances are void of any carcinogenic potential and do not require a classification in accordance with regulation (EC) 1272/2008.