Post crystallisation of ammonium sulfate aqueous phase products resulting from ammoniac neutralisation of sulfuric acid waste waters formed during methylmethacrylate synthesis

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

The potential toxic effects of the test item were evaluated in an OECD 421 study following daily oral administration (gavage) to male and female rats from before mating, through mating and, for females, through gestation until day post-partum (p. p.)(Chevalier, 2010). This study should provide information on all aspects of reproduction and development. Three groups of 10 male and 10 female Sprague-Dawley rats received the test item by daily oral (gavage) administration for 15 days before mating, through mating, gestation and the beginning of the lactation period (until day 4post-partum, p. p.). The dose-levels were 62.5, 250 and 1000 mg/kg/day. Another group of 10 males and 10 females received the vehicle, purified water, alone, under the same experimental conditions and acted as a control group. The dosing volume was 5 mL/kg. The concentration of test item in the dosage forms was checked at regular intervals. Clinical signs and mortality were checked daily. Body weight and food consumption were recorded at designated intervals throughout the study. Males were sacrificed after the end of the mating period (at least 5 weeks of treatment in total), females on day 5p. p.The adults were subjected to a macroscopic post-mortem examination of the principal thoracic and abdominal organs. Designated organs from adult animals were weighed. In addition, the numbers of corpora lutea and implantation sites were recorded for each female. A microscopic examination of the reproductive organs (epididymides, ovaries with oviducts and testes) of the control and high-dose animals was performed. The pups were observed daily for clinical signs, sexed and weighed on days 1 and 5p. p.After their sacrifice on day 5p. p.,they were examined to detect gross external abnormalities and a macroscopicpost-mortemexamination was performed.

The test item concentrations in the administered dosage forms were within the acceptable range of -9% to -4% of variation compared to the nominal values. There were no treatment-related clinical signs during the study, soft feces in 1/10 males given 250 or 1000 mg/kg/day and soiled urogenital area in 1/10 males given 1000 mg/kg/day being noted transiently during the pre-mating period. During the pre-mating period (days 1 to 15), males given 250 or 1000 mg/kg/day gained less weight than controls. Since these variations were transient and did not impacted the final body weight, there were not considered to be of toxicological importance. During the rest of the study, the body weight gain was unaffected and food consumption was similar between the test item‑treated male groups and the controls. During gestation, none of the variations of body weight gain recorded were statistically significantly different from the control values. Food consumption of test item-treated females was not affected during the study. There were no effects of treatment on mating at any dose-level. The male and female fertility indices were unaffected by treatment; all pregnant females had live pups. The duration of gestation was similar in the control and test item-treated groups and close to the normal value of 21 days. There were no effects of treatment on the mean number of live born pups or on pup death after birth. There were no gross external pup abnormalities in the control or test item-treated groups. The high pre-implantation losses recorded in a single female at 1000 mg/kg/day (which delivered only three pups) was considered to be isolated, and thus a relationship to treatment with the test item was unlikely. No differences of toxicological importance were noted in the male and female pup body weight gains. No relevant macroscopic findings were observed in the pups sacrificed on day 5 post‑partum. No treatment-related changes were observed in the testes or epididymides weights. There were no necropsy findings that could be ascribed to the test item treatment. At microscopic examination, there were no treatment-related changes in epididymides, testes or ovaries from treated animals when compared with controls. The test item was administered to male and female Sprague-Dawley rats by oral route (gavage), under the above detailed experimental conditions, at dose-levels of 62.5, 250 or 1000 mg/kg/day. At 1000 mg/kg/day during the pre-mating period, there were no treatment-related clinical signs, and the body weight gain of males was transiently lower than in controls in week 2 without consequences on the terminal body weight of males. There were no statistically significantly differences in the body weight of test item-treated females when compared to control mean values. One out of ten females from the high‑dose group had a low number of corpora lutea, high pre‑implantation loss and delivered only three pups, but this observation was not considered to be treatment-related. There were no substance-induced effects on male or female reproductive performance or on the progeny of the parental rats at any dose-level. Daily oral administration of the test item at the dose-level of 1000 mg/kg/day in the conditions of the study did not induce any treatment-related changes in the examined testes and epididymides in males or in ovaries in females. Based on the experimental conditions of this study and the isolated findings recorded at 1000 mg/kg/day, the dose-level of 1000 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and for reproductive performance (mating and fertility).

Short description of key information:
The potential toxic effects were evaluated in a reproduction/developmental toxicity screening test by oral route (gavage) in rats. The dose-level of 1000 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and developmental toxicity.

Effects on developmental toxicity

Description of key information

The potential toxic effects were evaluated in a reproduction/developmental toxicity screening test by oral route (gavage) in rats. The dose-level of 1000 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and developmental toxicity.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

See discussion "effects on fertility"

Justification for classification or non-classification

No classification is warranted for reproductive toxicity under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.