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EC number: 229-175-3 | CAS number: 6422-83-9
- Reproduction / developmental toxicity screening test, oral (gavage), rat (Crl:WI(Han)) m/f (OECD TG 421; GLP), dose levels: 0, 10, 30, 60 mg/kg bw/d: parental NOAEL: 60 mg/kg; fertility NOAEL, females: 60 mg/kg; developmental NOAEL: 60 mg/kg bw
In a Reproduction/Developmental Toxicity Screening Test according to OECD guideline 421 (adopted July 2015) 2,4-Bismaleimidotoluene (100% a.i.) was administered to groups of 10 Wistar rats/sex/dose by gavage at dose levels of 0, 30 and 60 mg/kg bw/d.
The mean number of corpora lutea was not significantly different from that in the dose groups compared with the control animals. However, a slightly reduced fertility index (number of females pregnant / number of females copulated X 100) of 80 % in the MD group compared to 90 % in all other groups. In the absence of dose response dependency, the finding was not considered to be of toxicological relevance.
During the treatment period of this study, few mortalities/moribund sacrifice were observed. Histopathologically, the cause of death/morbidity in two animals was considered to be due to gavaging error (tracheal inflammation, thymic inflammation with plant particles). The cause of death/morbidity could not be established for the other animals. The deaths were considered not treatment related.
Diarrhoea and moving the bedding as predominant clinical signs were observed in males and females. Other observed clinical signs were also present in the control group and, thus, considered incidental. Moving the bedding was observed transiently after dosing in the MD and HD and therefore considered to be a sign of discomfort due to local reaction to the test item rather than a systemic adverse effect.
No test item related or statistically significant effect on food consumption was observed in males and females during the whole study period, except for a statistically significant increase in group mean food consumption in female MD group observed during premating day 7-14 when compared with the controls. Due to lack of dose dependency and consistency, this statistically significant effect on female food consumption was considered to be incidental and not related to the treatment with test item.
There were no effects on the survival of the pups from PND 1 through PND 13 in the dose groups when compared to the control group. A marginally higher mean mortality of pups between PND 4 and PND 13 was observed in the HD group (1.01%) compared to the control group (0.00%).However, this effect did not achieve statistical significance. There were also few mortalities/missing pups observed from LD and MD group, and as a result a higher mean mortality of pups between PND 0 and PND 4 was observed in the LD and MD groups (2.81 and 0.89 %, respectively) compared to the control group (0.00%). Due to lack of dose dependency and consistency, this effect in LD and MD group was not considered to be treatment related.
No treatment-related changes were noted in any of the remaining parameters investigated in this study (i.e. body weight development, estrous cycle, litter data [ total number of pups born, number of male pups, number of female pups, sex ratio, number of live pups, still births and runts on PND 0 as well as number of male pups, number of female pups, number of live pups and sex ratio on PND 4 and PND 13], litter weight, precoital interval and duration of gestation, pre- and post-natal data [ number of corpora lutea, number of implantation sites, number of live pups (PND 0, PND 4 and PND 13) and percentage of pre- and post-implantation loss], thyroid hormone analysis, macroscopic changes, organ weights, gross lesions).
Based on these results, the following NOAELs were derived:
parental NOAEL: 60 mg/kg
fertility NOAEL, females: 60 mg/kg
developmental NOAEL: 60 mg/kg
Based on the results of the existing relevant study with 2,4 -Bismaleimidotoluene does not need to be classified for toxicity to reproduction, developmental toxicity and teratogenicity according to the criteria given in regulation (EC) 1272/2008. Therefore labelling is not necessary.
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