Tricobalt dicitrate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No reliable data available.

Additional information

There are no data available on toxicity to reproduction of Tricobalt dicitrate. However, there are reliable data available for structurally related cobalt compounds. Thus, read-across was conducted based on structural analogues.

Groups of rats and mice were exposed to cobalt(II)sulfate heptahydrate aerosols by inhalation at concentrations of 0, 3, 10, 30 mg/m3 (calculated as the anhydrous salt; equivalent to 3.6, 11.9, 35.7 mg/m3 Tricobalt dicitrate)

6 hours/day, 5 days/week, for 13 weeks (Bucher, 1991).

In rats, no significant effects on the male or female reproductive systems were observed. The NOAEC was determined to be 30 mg/m3 corresponding to 35.7 mg/m3 Tricobalt dicitrate (recalculated value).

2/10 male mice exposed to 30 mg/m3 died before termination of the study. At 30 mg/m3, significant atrophy of the testes was found. A significant decrease in sperm motility was observed at 3, 10 and 30 mg/m3 and the number of abnormal sperm was significantly increased in male mice exposed to 30 mg/m3. In female mice, the length of the estrous cycle was significantly increased at 30 mg/m3. No NOAEC for toxicity to reproduction was identified. The local LOAEC was determined to be 3 mg/m3 (equivalent to 3.6 mg/m3 Tricobalt dicitrate).

In addition, numerous animal data also show reproductive toxicity: both rats and mice exposed to soluble cobalt salts via drinking-water or diet exhibited testicular degeneration and atrophy (for example Nation et al., 1983; Domingo et al., 1984; Pedigo et al., 1988; Anderson et al., 1992, 1993).

References:

Nation, JR et al., 1983, The effects of chronic cobalt exposure on behaviour and metallothionein levels in the adult rat. Neurobehavioral Toxicology and Teratology, 5: 9 -15

Domingo, JL et al., 1984, A study of the effects of cobalt administered orally to rats. Archivos de Farmacologia y Toxicologia, 10: 13 -20

Pedigo, NG et al., 1988. Effects of acute and chronic exposure to cobalt in male reproduction in mice. Reproductive Toxicology, 2: 45 -53

Anderson, MB et al., 1992, Histopathology of testes from mice chronically treated with cobalt. Reproductive Toxicology, 6: 41 -50

Anderson, MB et al., 1993, Protective action of zinc against cobalt-induced testicular damage in the mouse. Reproductive Toxicology, 7: 49 -54

Short description of key information:
NOAEC (local, rat): 35.7 mg/m3 (Tricobalt dicitrate; recalculated value)
NOAEC (local, mouse): no NOAEC was identified
LOAEC (local, mouse): 3.6 mg/m3 (Tricobalt dicitrate/L; recalculated value)

Effects on developmental toxicity

Description of key information

The available data on developmental toxicity/teratogenicity are inconclusive and not sufficient for classification.

Additional information

There are no data available on toxicity to reproduction of Tricobalt dicitrate. However, there are reliable data available for structurally related cobalt compounds. Thus, read-across was conducted based on structural analogues.

The study of Szakmary et al. (2001) showed that exposure of pregnant rats to cobalt(II)sulfate heptahydrate at ≤ 100 mg/kg bw/day (calculated as the anhydrous salt; equivalent to 119 mg/kg bw/day Tricobalt dicitrate) did not affect fetal death rates, maternal body weight gain, average litter size, or average fetal and placental weights. However, a dose-related increase was noted in the percentage of fetuses with retarded body weights. The NOAEL for embryotoxicity/teratogenicity was determined to be 25 mg/kg bw/day corresponding to 30 mg/kg bw/day Tricobalt dicitrate. Based on significantly altered haematological parameters, the NOAEL for maternal toxicity was 50 mg/kg bw/day corresponding to 59 mg/kg bw/day Tricobalt dicitrate. It is concluded that cobalt sulfate exposure decreases the perinatal viability of the fetuses, but the functions of the surviving fetuses with perinatal retardation become compensated by postnatal week 2-3. The development of fetuses is undisturbed thereafter.

In contrast, Paternain et al. (1988) found no effects on fetal growth or survival after exposing rats to cobalt(II)chloride during gestation days 6 -15. Oral exposure of female rats to cobalt(II)chloride from gestation day 14 to lactation day 21 caused newborn pups to exhibit stunted growth and decreased survival. However, these effects occured at exposures that also caused maternal toxicity (reduced body weight and altered haemtological parameters). No teratogenic effects were observed (Domingo et al., 1985).

Exposure of pregnant mice to cobalt(II)sulfate heptahydrate at 50 mg/kg bw/day (calculated as the anhydrous salt; equivalent to 59 mg/kg bw/day Tricobalt dicitrate) also did not affect litter size, postimplantation loss, or average fetal and placental weights (Szakmary et al., 2001). Rabbits exposed to cobalt(II)sulfate heptahydrate at doses of ≥ 100 mg/kg bw/day (calculated as the anhydrous salt; equivalent to 119 mg/kg bw/day Tricobalt dicitrate) exhibited complete maternal lethality and fetal loss. At 20 mg/kg bw/day (calculated as the anhydrous salt; equivalent to 24 mg/kg bw/day Tricobalt dicitrate), rabbits had increased mortality, fetal resorption, and number of fetuses with retarded body weight (Szakmary et al., 2001).

References:

Paternain JL et al., 1988, Developmental toxicity of cobalt in the rat. Journal of Toxicology and Environmental Health, 24: 193 -200

Domingo JL et al., 1985, Effects of cobalt on postnatal development and late gestation in rats upon oral administration. Revista Espanola de Fisiologia, 41: 293 -298

Toxicity to reproduction: other studies

Additional information

No reliable data available.

Justification for classification or non-classification

There are no data available on toxicity to reproduction of Tricobalt dicitrate. However, there are reliable data available for structurally related cobalt compounds. Thus, read-across was conducted based on structural analogues.

DSD: Reproductive toxicity category 2; R60

CLP: Reproductive toxicity category 1B