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Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information
A reproduction/developmental screening study was conducted on MV31 by the oral route of exposure.  The result of the study was: 
The parental reproduction and developmental No Observed Adverse Effect Level (NOAEL) was 1000 mg/kg/day.
Additional information

The reproductive and developmental toxicity potential of MTDID 9580 (Clear colorless liquid, Purity 97.8%, Batch 113F1114 (E27136)) was evaluated in Wistar Han rats. METHODS: The study was conducted in compliance with OECD GLP (1997) regulations. The test method was based on OECD 421 (1995) and OPTS 870.3550 Reproduction/Developmental Toxicity Screening Test (2000). The test article in polyethylene glycol 400 was administered via oral gavage at 0 (vehicle), 150, 450, or 1000 mg/kg/day to 10 animals/sex/group at a dose volume of 5 mL/kg body weight. Males were exposed for 2 weeks prior to mating, during mating, and up to termination (for 28 days). The females were exposed for 2 weeks prior to mating, during mating, during post-coitum, and at least 4 days of lactation (for 40-44 days). For the parental animals, mortality/viability (at least twice daily), clinical signs (daily), body weights (Males: Day 1 of exposure, and weekly thereafter. Females: Days 0, 4, 7, 11, 14, 17, and 20 post coitum and lactation Days 1 and 4) food consumption (weekly), and general reproduction data (at post-coitum day 0 and birthing for mothers) were noted. For pups, mortality/viability (daily), clinical signs (at least once daily), body weights (Day 1 and 4 of lactation), sex determination (Day 1 and 4 of lactation), and external examination (at sacrifice) were noted. Parental animals were subject to gross necropsy and the ovaries, testes, epididymides of animals in the control and 1000 mg/kg/day groups were collected and examined by a histopathologist. RESULTS: In parental animals, no mortality occurred during the study period. No toxicologically relevant clinical signs, changes in body weights or body weight gains, or food consumption were noted during the study. Upon macroscopic examination, no toxicologically relevant alterations were observed. The testes, epididymides weights and terminal body weights of treated males were similar to those of control animals. Upon microscopic examination of the selected tissues, histologic changes were considered to be incidental findings. There was no test article-related alteration in the prevalence, severity, or histologic character of those incidental tissue alterations. No toxicologically relevant effects on reproductive parameters were noted. Mating, fertility and conception indices, precoital time, and number of corpea lutea and implantation sites were unaffected by treatment. Two females at 150 mg/kg/day failed to deliver healthy offspring (these did not mate and/or did not become pregnant). Since the incidence of infertile animals showed not dose-response relationship, the findings were considered incidental. No toxicologically relevant effects on gestation index and duration, parturition, maternal care and early postnatal pup development (mortality, clinical signs, body weight and macroscopy) were observed. CONCLUSION: Based on the results of the study, the parental reproduction and developmental No Observed Adverse Effect Level (NOAEL) was 1000 mg/kg/day.

Justification for classification or non-classification

The results of the test do not meet the requirements to classify MV31 as a reproductive toxicant.