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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Additional information

Reproductive/developmental toxicity

Reproductive toxicity

[SIDS data] Oral toxicity study was performed in SD (Crj: CD) rats by an OECD combined repeated dose and reproductive/developmental toxicity screening test (OECD TG 422). Administration was conducted by gavage at doses of 10, 30 and 100 mg/kg/day from 14 days before mating to 14 days after mating in males and from 14 days before mating to day 3 of lactation in females. (MHW, Japan: 1997)

The fertility index (number of delivered animals/ number of mated animals) decreased significantly at 100 mg/kg. There were no effects on the estrous cycle, copulation index, or gestation length. No significant changes in the numbers of corpora lutea, implants, pups born and live pups as well as the implantation and delivery indices were observed. There were no significant differences in the gestation index, live birth index or viability index on day 4. Histopathological analysis of the gonads showed no significant effect considered to cause infertility in all treatment groups. No change in the number of gonocyte per Sertoli cell was observed in epithelium of seminiferous tubule (stage VIII) of all survival males at 100 mg/kg. No abnormalities attributable to the administration of this chemical were noted in the body weights of live pups or on necropsy of pups in any treated group. Therefore, NOAELs for reproductive performance of parents and pup development were considered to be 30 mg/kg/day and 100 mg/kg/day, respectively. This key study was used for the derivation of the fertility DNEL.

Male mice injected i.p. with 5 consecutive daily doses of 0, 25, 50 or 100 mg/kg/day showed an increase in the percentage of abnormal sperm and decrease in the number of sperm (Xie et al.: 1990). These results were confirmed in a subsequent study where mice were dosed i.p. with 0, 5, 25 or 100 mg/kg for five consecutive days (Vedula et al., 1994). At 100 mg/kg, mice had decreased caudal epididymal weights, slightly lower testicular weights, decreased sperm counts and increased abnormal sperm. Mice given 25 mg/kg/day showed decreased sperm counts and increased abnormal sperm. These results might support the decreased fertility index of rat study at 100 mg/kg/day.

Developmental toxicity

Glycidyl methacrylate was administered by gavage to rats during day 5 to day 15 of gestation at doses of 5.38, 10.76, 21.52 and 108.0 mg/kg/day. The animals were sacrificed on day 19 of pregnancy. (OuYang et al.: 1988)

As maternal toxicity, there was significant decrease in body weight gain at 108.0 mg/kg. There was a statistically significant increase in the fetal resorption rate at the 108.0 mg/kg. The percentage of pups stillborn was somewhat higher than control at all dose levels. However, because this change was not dose-dependent and statistically significant change was only at 10.76 mg/kg, this was not considered to be chemical-related change. Neither birth defects nor fetal abnormalities were noted in rats treated with this chemical. There was also no significant difference in fetal body weight from the control. Therefore, NOAELs were considered to be 21.52 mg/kg/day for maternal toxicity and 108.0 mg/kg/day for teratogenicity.

There were two inhalation tests on developmental toxicity.

Rabbits were exposed to glycidyl methacrylate at concentrations of 29.1, 58.2 and 291 mg/m3, 6 hours/day, daily during day 7 to day 19 of gestation (Vedula et al.: 1995). Daily intake is calculated as 2.62, 5.24 and 26.2 mg/kg/day. Respiratory distress and decrease in feed consumption was observed at 291 mg/m3. Less severe signs of ocular and respiratory irritation consisting of reddened eyes, wet muzzle and sneezing after exposure were observed at 58.2 mg/m3. Treatment-related histopathologic alterations of the nasal tissues (hyperplasia, necrosis, etc.) were present in all animals treated with this chemical. Because of respiratory distress, animals at 291 mg/m3 were removed early from study after the third exposure. Therefore, evaluation of reproductive and embryonal/fetal parameter was precluded. There was no adverse effect on any reproductive and embryo/fetal parameter at 29.1 and 58.2 mg/m3. LOAEL for maternal toxicity was 29.1 mg/m3 (2.62 mg/kg/day) and NOAEL for teratogenicity was 58.2 mg/m3 (5.24 mg/kg/day).

Rabbits were also exposed to glycidyl methacrylate at concentrations of 2.91, 11.6 and 58.2 mg/m3, 7 hours/day, daily during day 7 to day 19 of gestation (Vedula et al.: 1995). Daily intake is calculated as 0.31, 1.22, 6.11 mg/kg/day. The principal indication of maternal toxicity was inflammation of the nasal olfactory and respiratory epithelium at the 11.6 and 58.2 mg/m3. There was no adverse effect on any reproductive and embryo/fetal parameter at any doses. Therefore, NOAEL for maternal toxicity was 2.91 mg/m3 (0.31 mg/kg/day) and NOAEL for teratogenicity was 58.2 mg/m3 (6.11 mg/kg/day).

As three reliable developmental studies by two different routes, oral and inhalation, indicated no teratogenicity even at the highest doses which showed the maternal toxicity, glycidyl methacrylate is not considered to have developmental toxicity.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
108 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
58.2 mg/m³

Justification for classification or non-classification

Based on the available studies classification under REACH and CLP of glycidyl methacrylate for developmental toxicity is not required.

However based on the same studies the substance must be classified under these Regulations as Toxic to Reproduction Category 1B (H360F), the cause probably being its metabolism to glycidol.

Additional information

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