Registration Dossier
Registration Dossier
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EC number: 227-873-2 | CAS number: 6018-92-4
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Additional information
There are no reproduction studies for Trinickel dicitrate. However, extensive data exist for the read-across substance nickel sulphate.
The data are taken from the EU-RAR for nickel sulphate, dated 2008.
Two oral multi-generation reproduction studies and a range-finding one-generation study of nickel sulphate hexahydrate are available (Ambrose et al. 1976, SLI 2000a, SLI 2000b). No effects on fertility have been found in these studies following oral administration; no data are available for inhalation and dermal contact. The 3-generation study by Ambrose et al. (1976) and the one-generation range-finding study (SLI 2000a) indicate NOAELs of 1000 ppm and 500 ppm, respectively. However, the Ambrose et al. study has a limited reporting of data and the range-finding study uses only a limited number of animals (8 per group). Therefore, the most reliable NOAEL is from the recent OECD TG 416 two-generation study (SLI 2000b) where the NOAEL is the highest dose investigated, i.e. 10 mg nickel sulphate hexahydrate/kg bw/day. Effects on male sex organs in rats and mice have been reported in limited studies after oral (Waltschewa et al. 1972, Sobti and Gill 1989), inhalation (Benson et al. 1988) or subcutaneous (Hoey 1966) administration. These studies indicate a possible LOAEL and LOAEC for oral and inhalation exposure of 25 mg nickel sulphate/kg bw/day and 1.6 mg Ni/m3, respectively. A repeated dose toxicity study provides a NOAEL for effects on sperm and oestrus cyclicity of 2.0 mg nickel sulphate/m3after inhalation exposure (Dunnick et al. 1989). No effects on male sex organs including sperm quality were found in the recent oral OECD TG 416 two-generation study (SLI 2000b) and the NOAEL is therefore the highest dose studied, i.e. is 10 mg nickel sulphate hexahydrate/kg bw/day.
References:
Benson JM, Burt DG, Carpenter RL, Eidson AF, Hahn FF, Haley PJ, Hanson RL, Hobbs CH, Pickrell JA, Dunnick JK (1988): Comparative inhalation toxicity of nickel sulphate to F344/N rats and B6C3F1 mice exposed for 12 days. Fundam Appl Toxicology 10: 164-178.
Hoey MJ (1966): The effects of metallic salts on the histology of functioning of the rat testis. J Reprod Fertil 12: 461-471.
SLI (2000a): An oral (gavage) 1-generation reproduction study of nickel sulfate hexahydrate in rats. Study No. 3472.1 carried out for NiPERA. Springborn Laboratories, Inc. Spencerville, Ohio, USA.
SLI (2000b): An oral (gavage) two-generation reproduction toxicity study in Sprague-Dawley rats with nickel sulphate hexahydrate. Study No. 3472.2 carried out for NiPERA. Springborn Laboratories, Inc. Spencerville, Ohio, USA.
Sobti RC, Gill RK, (1989): Incidence of micronuclei and abnormalities in the head of spermatozoa caused by the salts of a heavy metal nickel. Cytologica 54: 249-254.
Short description of key information:
Oral:
LOAEL = 17.5 mg/kg bw/d Trinickel dicitrate
Inhalation:
NOAEC = 1.423 mg/m3 Trinickel dicitrate
LOAEC = 5.03 mg/m3 Trinickel dicitrate
Effects on developmental toxicity
Description of key information
LOAEL = 39.58 mg/kg bw/d Trinickel dicitrate
Additional information
There are no reproduction studies for Trinickel dicitrate. However, extensive data exist for the read-across substance nickel sulphate.
The data are taken from the EU-RAR for nickel sulphate, dated 2008.
Developmental toxicity / teratogenicity
A 3-generation reproduction study in Wistar rats was briefly described by Ambrose et al. (1976). Groups of 30 weanling rats per sex per group were fed 0, 250, 500, or 1000 ppm nickel as nickel sulphate hexahydrate for 11 weeks. Body weights of the F0 rats were decreased only at the high dose, with an average decrease of 8% reported for females. The number of pups born dead was increased at all nickel doses in the F1a generation and at 500 ppm and 1000 ppm in the F1b generation, but there was no effect on pup mortality in later generations. There was a clear and consistent decrease averaging 27% in mean weanling body weight at 1000 ppm in all generations. The study authors state that there was no evidence of teratogenicity, based on gross examinations, and no histopathologic effects on the F3b generation, but present no supporting data. Evaluation of this study is complicated by the lack of statistical analyses and the reporting of results using pups rather than litters as the unit. Statistical analysis of the number of pups born dead show that the increased numbers at all doses levels in F1a and at 500 and 1000 ppm in F1b is statistically significant.Justification for classification or non-classification
Based on the available data, Trinickel dicitrate needs to be classified:
EU: Reproduction category 2, R61
CLP: Category 1B reproductive toxicity
Additional information
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