Dichromium nitride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No information on the in vitro genotoxicity of chromium nitride is available. Therefore, a conservative read-across to the soluble chromium(III) salts category is applied as detailed in the read-across document attached to IUCLID section 13.

Soluble chromium(III) substances were assessed in a number of in vitro genotoxicity assays showing no genotoxic potential, clastogenic or aneugenic potency. Consequently, soluble chromium (III) salts are considered non genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No information on the in in vivo genotoxicity of chromium nitride is available. Therefore, a conservative read-across to the soluble chromium(III) salts category is applied as detailed in the read-across document attached to IUCLID section 13.

Soluble chromium(III) substances were assessed in a number of in vivo genotoxicity assays showing no genotoxic potential. Consequently, soluble chromium (III) salts are considered non genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

No information on the genotoxicity of chromium nitride is available. Therefore, a conservative read-across to the soluble chromium(III) salts category is applied.

in vitro studies

In two NTP studies (NTP, 2010) chromium picolinate was evaluated for bacterial mutagenicity in strains of Salmonella typhimurium (TA98, TA100, TA1535, TA97, TA102, TA104 and TA100, TA98, E. coli WP2 uvrA/pKM101) using the pre-incubation method. Five concentrations were tested in triplicate in the absence and presence of S9 in 2 independent experiments. Chromium picolinate (up to 10,000 μg/plate) gave a negative response in all strains in the presence and absence of S9 activation mix.

 

Whittaker et al. (2005) tested chromium(III) chloride at 100, 333, 1000, 3333 and 10000 µg/plate with and without metabolic activation in Salmonella typhimurium TA98, TA100 and TA1535 in triplicate cultures using the pre-incubation method. Chromium(III) chloride gave a negative response in all strains in the presence and absence of S9 activation mix.

 

Chromium(III) chloride has been tested for induction of tk mutations in mouse lymphoma L5178Y cells (Whittaker 2005). Treatments were for 4 hr hrs in the absence and presence of S9. Chromium chloride was negative in the in vitro mouse lymphoma assay (tk mutation) in L5178Y cells, when tested up to cytotoxic concentrations (RTG <20%) in the absence and presence of metabolic activation. A slight but not statistically significant increase in the mutant frequency was seen in the highest dose tested with metabolic activation. Since this increased mutation frequency was seen only at the highest dose with severe cytotoxicty, it is regarded as not biologically relevant. Consequently chromium(III) chloride is considered negative in the in vitro mouse lymphoma assay.

 

Slesinski, R.S. et al. (2005) assessed the mutagenic potential of chromium(III) chloride. Duplicate cultures of exponentially growing CHO–K1 cells were exposed for 5 hours to concentrations of chromium(III) chloride and control materials with and without S9 activation. In both the non-activated and S9-activated systems, 100 cells/plate, from cultures treated with concentrations of 15.6, 31.3, 62.5, 125, 250, and 500 µg/mL of the test item, were cloned in medium without 6-TG to determine concurrent cytotoxicity. Visible precipitate was visible only at 500 µg/mL. The lowest relative cloning efficiency was 25% at 500 µg/mL. No mutant frequencies of greater than 40 mutants/10E6 clonable cells were observed at any dose level and all increases above the concurrent solvent control values were within the normal range of variation seen in this test system. No increase mutation frequency was seen when tested up to precipitating concentrations with and without metabolic activation.

 

 

in vivo studies

In a 13 week (5 days per week) oral repeated dose toxicity study with 5 different doses of chromium picolinate, the MN frequency was measured in the peripheral blood of mice (NTP, 2010) . The frequency of micronucleated cells in 1000 normochromatic erythrocytes (NCEs) in each of 10 animals per exposure group was determined. No increase in the frequency of micronucleated normochromatic erythrocytes was observed in male B6C3F1 mice administered chromium picolinate monohydrate in feed for 3 months, indicating no potential for inducation of chromosomal alterations. In female mice, however, the small increase in micronucleated normochromatic erythrocytes noted in the highest exposure concentration group (50,000 ppm) was not significant at P=0.0396. There were no clinical findings in male or female animals, related to exposure to chromium picolinate monohydrate; reddish-colored faeces of 50000 ppm animals were believed to be due to excretion of the test article and were not considered a sign of toxicity. All mice survived to the end of the study. Consequently, chromium picolinate is considered non clastogenic and non aneugenic in this in vivo assay.

 

Five male rats were treated with chromium picolinate three times during 72 hrs orally and sacrificed 24 hrs after final treatment. 2000 polychromatic erythrocytes were scored for the frequency of micronucleated cells in each of five rats per dose group. No induction of micronucleated polychromatic erythrocytes was observed in bone marrow of male F344/N rats treated with chromium picolinate (156 to 2,500 mg/kg) by oral gavage three times at 24-hour intervals, and no significant alterations in the percentage of polychromatic erythrocytes among total erythrocytes was observed in dosed rats, indicating that these doses of chromium picolinate did not induce bone marrow toxicity. Consequently, chromium picolinate is considered non clastogenic and non aneugenic in this in vivo assay.

 

In an in vivo chromosome aberration assay in bone marrow, male and female SD rats were treated once with chromium picolinate orally via gavage at concentrations of 33, 250 and 2000 mg/kg bw. Animals were sacrificed 18 and 42 hrs after dosing. In all test item-treated groups there were no differences in frequency of chromosomal aberrations when compared to vehicle controls. The rats treated with the test item presented no significant differences in mean mitotic index compared with the vehicle control group. The mean total number of chromosomal aberrations in test item groups treated rats displayed no significant differences. The positive control, induced a significant amount of chromosomal damage in both males (30%) and females (37%) that were statistically different from all test item doses and from the vehicle control. Consequently, chromium picolinate is considered non clastogenic in this in vivo assay.

 

Conclusion

The available data on genetic toxicity allow a conclusive statement on the genetic toxicity for the soluble chromium(III) salts category. There is no convincing evidence that the chromium(III) salts category induce gene, chromosome or genome mutations either in bacterial or in mammalian cells let alone in in vivo systems. Overall, there is no consistent evidence of induction of genetic toxicity with relevance to humans for the soluble chromium(III) salts category.

Justification for classification or non-classification

In consideration of the negative test results in highly reliable genotoxicity assays with the soluble chromium(III) salts category, no genotoxicity needs to be expected from exposure to the target substance chromium nitride. In consequence, no classification is required.