Pyrazole

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

no data available

Effects on developmental toxicity

Description of key information

oral
rat, gavage: NOAEL maternal toxicity = 1 mg/kg bw/d; NOAEL fetotoxicity = 5 mg/kg bw/d; NOAEL teratogenicity 15 mg/kg bw/d (GLP; TSCATS OTS0519140, 1989)
rat, gavage, range finder: LOAEL maternal/ fetotoxicity/ teratogenicity = 25 mg/kg bw (GLP; Holson, 1989)

Additional information

In a GLP conform oral developmental study in rats, the test substance (purity 98.0%; in corn oil) was administered to groups of 8 Sprague-Dawley rats in doses of 0, 1, 5, 10, 15 or 20 mg/kg/day during gestation day 6 to 15 per gavage. The test substance causes developmental as well as maternal toxicity in rats at dose levels >= 10 mg/kg/day. No mortality occurred at any dose level. Substantial body weight losses were noted at 15 and 20 mg/kg/day. Slight to moderate mean body weight effects occurred at 10 and possibly 5 mg/kg/day, primarily during the first 3 days of dosing. A dose related decrease in mean fetal weights was apparent at >= 10 mg/kg/day. The only external malformations observed were cleft palate in 6 fetuses from 2 litters at 20 mg/kg/day. The NOAEL for maternal toxicity was identified as 1 mg/kg/day, the NOAEL for fetotoxicity as 5 mg/kg/day and the NOAEL for teratogenicity as 15 mg/kg bw (TSCATS OTS0519140, 1989).

In a GLP conform range finding study for an oral developmental study in rats, the test substance (purity 98.0; in corn oil) was administered to groups of 8 Sprague-Dawley rats in doses of 25, 100, 175 and 225 mg/kg/day during gestation day 6 to 18 per gavage. All dose levels examined were considered excessive for a definitive developmental toxicity study in rats with the test substance based on the strong maternal (lowest dose with multiple clinical signs; two highest doses with 100% mortality) and fetal toxicity (postimplantation loss and reduced fetal weight in the lowest dose) expressed at these dose levels. The NOAEL for both the maternal and the developmental toxicity is identified as < 25 mg/kg bw/day (Holson, 1989).

In an oral developmental study in rats with inconvenient study design, the test substance (purity unknown; in saline) was administered to two Sprague-Dawley rats in a dose of 100 mg/kg/day on gestation day 6, 9 and 12 per gavage. The test substance, a potent inhibitor of alcohol dehydrogenase, induced a high incidence of ocular and urinary bladder anomalies in the offspring of rats following treatment on gestational day 9. A single moderate dose of ethanol potentiated the teratogenic action of the test substance, but alone did not affect embryonic development (Varma et al., 1979).

In an intaperitoneal developmental study in mice with an inconvenient study design, the test substance (purity unknown; in saline) was administered to Swiss Webster in a dose of 6 mg/kg/day on gestation days 8, 10, 12 and 14. In order to learn more about the possible metabolic determinants of the fetal alcohol syndrome, the effects of inhibitors of alcohol dehydrogenase on the transplacental embryotoxicity and teratogenicity of ethanol were studied. Both ethanol and test substance administered separately had embryocidal effects but the test substance was the more potent compound. Ethanol and pyrazole administered together were less embryocidal than the test substance alone; both reduced fetal weight when administered alone but had no effect when injected jointly. The test substance derivatives were not embryocidal in the dose of 6mg/kg. Combined treatment of pregnant dams with ethanol and either of the two the test substance derivatives resulted in increased fetal mortality. Neither of the two the test substance derivatives when given alone affected the fetal weight. When given together with ethanol, both derivatives reduced the fetal weight (Giknis et al., 1982).

In a developmental study in hens with an inconvenient study design, the test substance (purity unknown; in saline) was injected into 15 eggs of hens in a dose of 0.1 mg/egg. All embryos survived, but 6 % showed hemorrhages and everted viscera. The test substance did not significantly influence the development of the chick embryo (Gilani et al., 1986).

Justification for classification or non-classification

According to the conditions of the available results, there is no indication given for developmental toxicity in doses below maternal toxic doses. Therefore, pyrazole has not to be classified according to 67/548/EEC and GHS requirements (EG 1272/2008), respectively.