Reaction mass of cobalt olivine and crystalline silicon dioxide

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

No studies on the toxicity to reproduction with Reaction mass of cobalt olivine and crystalline silicon dioxide are available, thus the toxicity to reproduction will be addressed with existing data on the relevant toxic unit cobalt. The source information is selected based on the read-across approach implemented by the Cobalt REACH consortium for oral systemic effects. Further details on the read-across approach are given in the report attached to IUCLID section 13.

Additional information

The toxicity to reproduction of Reaction mass of cobalt olivine and crystalline silicon dioxide is addressed with existing data on the source substances identified in the read-across of the cobalt category substances as defined by the Cobalt REACH Consortium.

Based on the approach for oral systemic effects assessment, the pigment Reaction mass of cobalt olivine and crystalline silicon dioxide is placed in the bioavailable cobalt substances group (BCoS) for the oral route. Due to the tonnage band of Reaction mass of cobalt olivine and crystalline silicon dioxide, not all information reported for toxicity to reproduction in the Cobalt REACH Consortium dossier for the cobalt category substances are available. However, the hazard conclusion as concluded for the bioavailable cobalt substances group (BCoS) are adopted for Reaction mass of cobalt olivine and crystalline silicon dioxide (please refer to the section “Justification for classification or non-classification”).

 

In a combined repeated dose toxicity studies with the reproduction/developmental toxicity screening test (according to OECD 422 and under GLP) cobalt was administered orally to rats at dose levels of 30, 100, 300 and 1000 mg/kg bw/day during the pre-mating, mating and post-mating periods to parental males as well as during the pre-mating, mating, gestation and lactation periods until day 3 post-partum (or shortly thereafter) to parental female animals.

Piloerection, reduced motility, soft faeces/diarrhoea and reduced food consumption were noted - in relation to the dose - from a dose level of 100 mg cobalt /kg bw/day onwards. In addition, reductions of body weight were noted from 300 mg cobalt /kg bw/day onwards. Premature deaths occurred in five female rats at 100 mg cobalt /kg bw/day and eight female rats at 300 mg cobalt /kg bw/day. Treatment with 1000 mg cobalt /kg bw/day caused the premature death of nine of ten males and all ten females. Macroscopic inspection revealed changes of the gastro-intestinal tract - mainly in the prematurely deceased animals - from a dose level of 100 mg cobalt/kg bw/day onwards and adrenal changes and pulmonal lesions at 1000 mg cobalt/kg bw/day.

Histopathological inspection did not reveal any pathological changes. No histopathological correlate could be found for the macroscopical lesions noted at necropsy. No test item-related influence was noted on the sperm staging or interstitial cell structure (qualitative examination). Treatment with 300 mg cobalt/kg bw/day resulted in an increase of the post-implantation loss and a decrease in the live birth index. No test item-related influence was noted on mating behaviour, fertility and the gestation length. From 30 mg cobalt/kg bw/day onwards, the mean litter weight of pups was slightly reduced in a dose-related way (not significant at p ≤ 0.01), significant only at 300 mg cobalt/kg bw/day. In order to estimate a possible correlation between maternal toxicity and F1-Generation (pups) findings, the litter weight of pups was compared in dams with clinical signs within each group. Dams were classified based on the severity and occurrence of clinical signs. As a result it appeared that the earlier the clinical signs occurred in the dams a more pronounced weight reduction was noted for the pups of the respective dams. An increased F1-Generation (pups) mortality rate and a slightly decreased viability index were noted from 100 mg cobalt/kg bw/day onwards.

The NO(A)EL for effects on the F0-generation was 30 mg cobalt/kg bw/day, based on mortality, clinical signs of toxicity, effects on food consumption and macroscopic pathological changes observed at and above 100 mg cobalt/kg bw/day and reduced body weight at and above 300 mg cobalt/kg bw/day.

The NO(A)EL for effects on the reproductive toxicity was 30 mg cobalt/kg bw/day, based on an increased F1-Generation (pups) mortality rate and a slightly decreased viability index at 100 mg cobalt/kg bw/day and on post-implantation losses, decreases in the live birth index and significantly reduced litter weights of pups observed at 300 mg cobalt/kg bw/day.

Justification for classification or non-classification

The hazard conclusion for Reaction mass of cobalt olivine and crystalline silicon dioxide for the endpoint toxicity to reproduction is adopted from the bioavailable cobalt substances group (BCoS), based on the read-across approach as outlined in the report attached to section 13.

The current test results for the bioavailable cobalt substances group (BCoS) does not support the identification of any adverse effects towards male reproductive organs for the bioavailable cobalt substances group. However, these is still existing information in the public domain which identified a hazard with regard to male reproduction. Consequently all members of the bioavailable cobalt substances group will be self-classified as toxic for reproduction category 1B (H360F). The available data on the repeated dose toxicity of the bioavailable cobalt substances group is adequate to support a robust risk assessment, by using the point of departure for the most sensitive systemic effect on the haematopoietic system.

The test results with the source substances of the bioavailable cobalt substances group (screening test with cobalt, pre-natal developmental toxicity study with cobalt dichloride in rats and rabbits) does not support the clear identification of adverse effects towards developmental toxicity. However, findings in the pre-natal developmental toxicity study in rabbits manifested as increased early resorptions at presence of some maternal toxicity does not allow to unequivocally conclude on an absence of developmental effects in rabbits. Consequently, cobalt dichloride and subsequently all members of the bioavailable cobalt substances group (BCoS) are self-classified for developmental toxicity Category 2 (H361d).