Phenylhydrazine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Non-human data:

One study assessing the effects on fertility of phenylhydrazine was available. In this study each of three dogs (one dog per dose group) received 20, 30, or 40 mg phenylhydrazine/kg body weight in saline by subcutaneous injection on 2 consecutive days (Witchett, 1975). Two control animals were not injected. At necropsy, performed on all three animals within a few days of dosing, a “striking” reduction in spermatogenesis was reported, with an absence of sperm in the epididymis. However, the validity of this result was not clear, given the apparent extreme rapidity of the effect.

Human data:

No data available

Short description of key information:
One study was available assessing potential toxicity effects of phenylhydrazine on fertility.

Effects on developmental toxicity

Description of key information

Three studies were available assessing potential developmental toxicity effects by phenylhydrazine. Phenylhydrazine was not conclusively considered teratogenic.

Additional information

Non-human data:

In a teratogenicity study groups of 8–12 pregnant Wistar rats were given an intraperitoneal injection of 7.5 mg phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on days 17, 18, and 19 of gestation; or 15 mg phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on days 18 and 19 of gestation (Tamaki et al., 1974). Control animals were not treated. There was no reporting of maternal toxicity or of the effect of treatment on gestation or pup viability. Toxicity of the pups was reported only insofar as there was incidence of jaundice and/or anaemia among the offspring of treated animals. Twelve male offspring with severe jaundice and anaemia, selected from treated dams, and nine males from control dams were assessed at 9–22 weeks of age for functional and behavioural status. Although the authors reported that experimental animals showed statistically significant differences from controls in some tests, these findings are not considered to be reliable because of the small numbers of animals used and the exclusion of a control animal from the analysis. In addition, it is noted that only a brief part of the gestation period was covered by the treatment regime (days 17–19); no explanation is available for this choice of dosing regime. 

In a second teratogenicity study intraperitoneal injection of pregnant rats with 15 mg phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on days 18 and 19 of gestation produced hyperbilirubinaemia (resulting from haemolysis) in foetuses and newborns were reported (Yamamura et al., 1973). 

In a third teratogenicity study to investigate behavioural changes on the rats from the dam treated with phenylhydrazine during pregnancy, groups of pregnant Wistar rats were given an intraperitoneal injection of 10 mg phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on days 17, 18, and 19 of gestation; or 20 mg phenylhydrazine/kg body weight as phenylhydrazine hydrochloride on days 18 and 19 of gestation (Kiyono et al., 1974). Results showed no consistent difference between the experimental and control animals. However, the mean duration of the epoch of paradoxical sleep showed a significant decrease in several experimental rats, suggesting that this might be a sensitive indicator to detect the long-lasting functional disturbance caused by the toxic drug during the perinatal period.

 

Human data:

No data available

Justification for classification or non-classification

Based on available of results for reproductive and developmental toxicity, phenylhydrazine was not classified and labelled according to Directive 677548/EEC (DSD) and to Regulation 1272/2008/EC (CLP).