Zinc bis(benzenesulphinate)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction: NOAEL = 400 mg/kg/day, based on changes of no toxicological significance at all dose levels.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A reproduction/developmental toxicity screening test in male and female Wistar rats was run at doses of 50, 200 and 400 mg/kg/day, according to OECD guideline 422.

Males were dosed during pre-mating period, mating period and after mating up to 49 days.

Females were dosed up to day 13 post-parturition.

Doses were selected in a DRFE of 21 days using non pregnant rats dosed at 150, 300, 600 and 1000 mg/kg/day.

No effect on physical growth of parental animals (body weight, body weight increment, food consumption) was seen in any phase of the study (before mating, during mating period, pregnancy and lactation period).  

Slight decrease of absolute and relative weight of epididymides, testes and prostate gland with seminal vesicles at treated males was recorded. Microscopical examination of reproductive organs and pituitary gland did not reveal presence of treatment related changes, only the spontaneous changes were found out.

In males, absolute and relative weight of thyroid gland was increased, at the dose levels 200 and 400 mg/kg/day statistically significantly. Suspected decreased volume of colloid and/or suspected condensation of colloid in thyroid gland was probably caused by the test substance administration. Serum level for thyroid hormone thyroxine was decreased in dose dependent manner, at the dose levels 200 and 400 statistically significantly. However, all findings mentioned above did not have influence to reproduction ability of males.

Microscopic examination of reproductive organs, thyroid gland and pituitary gland in females did not reveal presence of treatment related changes.

Examination of sperm motility and morphology in parental males showed worsened sperm quality in treated males in comparison with the control males, but the ability of males to fertilize the females was not affected.

Numbers of implantations and pups were not influenced by the test substance treatment at any dose level.

Overall, all changes seen in parental males and females at all dose levels were considered as devoid of a toxicological significance.

Effects on developmental toxicity

Description of key information

Developmental toxicity: NOAEL = 200 mg/kg/day, based on cannibalism and macroscopic findings at the dose level of 400 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A reproduction/developmental toxicity screening test in male and female Wistar rats was run at dose levels of 50, 200 and 400 mg/kg/d, according to OECD guideline 422.

In males, the dosing period was 49 -days; in females, the dosing period covered 15 days pre-mating, mating, gestation up to 13 days post-parturition. Doses were selected in a DRFE of 21 days using non pregnant rats dosed at 150, 300, 600 and 1000 mg/kg/day.

At the dose level of 400 mg/kg/day, increased cannibalism of pups was seen as well as macroscopical findings, e.g. malnutrition, empty stomach, marked flatulency of gastrointestinal tract, pink blood and moribund condition. Based on a dose-dependent increase, such effects were taken as possibly related to the treatment.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, adverse effects on development of the offspring and adverse effects on or via lactation.

Substances are classified in Category 1 for reproductive toxicity when they are known to have produced an adverse effect on sexual function and fertility, or on development in humans or when there is evidence from animal studies, possibly supplemented with other information, to provide a strong presumption that the substance has the capacity to interfere with reproduction in humans.

Substances are classified in Category 2 for reproductive toxicity when there is some evidence from humans or experimental animals, possibly supplemented with other information, of an adverse effect on sexual function and fertility, or on development, and where the evidence is not sufficiently convincing to place the substance in Category 1.

In a combined repeated dose and reproductive toxicity study, no significant effects on reproduction parameters of male and female rats were reported. Significant effects on general toxicity of parental animals were seen and led to the identification of a LOAEL at 50 mg/kg/day; a NOAEL of 400 mg/kg/day for reproduction was estabilshed.

Findings in pups were only noted at the dose of 400 mg/kg/day. In particular, it was noted:

- increase in cannibalism likely of unhealthy pups

- flatulency, pink blood, moribund condition, in some pups (not cannibalised).

It was excluded that increase of cannibalism at the dose of 400 mg/kg/day was due to inability of dams, as dams care well for healthy pups at the same dose level. Therefore, cannibalism along with unhealthy condition of some pups were considered as related to the treatment. However, based on available data it could not be excluded that effects on pups were a consequence of effects on dams. For instance, data on amount / quality of milk in lactation was not collected.

Overall, based on findings at 400 mg/kg/day, a NOAEL at 200 mg/kg and a LOAEL at 400 mg/kg were identified.

Based on available data, no classification for reproductive toxicity was applied.