Phenylhydrazine

Endpoint summary

Description of key information

Exposure to phenylhydrazine may cause damage to red blood cells, potentially resulting in anaemia and consequential secondary involvement of other tissues, such as the spleen and liver. 

Additional information

Non-human data:

Data on the oral repeated dose toxicity of phenylhydrazine were available for different species.

Kelly et al. (1969) administered phenylhydrazine hydrochloride to 21 mice by oral gavage once weekly for 8 weeks, at an estimated dose of 85 mg/kg bw/week. There were 10 saline-treated controls. There was 30 % mortality in treated mice compared with none in controls. Further the report described only tumour-related findings.

Haematological changes were reported in four dogs administered 60 mg phenylhydrazine/kg body weight, either as a single dose or as 2, 3, or 10 equal doses on consecutive days (Giffin & Allen, 1928). There was a marked reduction in erythrocyte count that was comparable in magnitude in all dogs at the end of 10 days, but that occurred at a faster rate after a single high dose compared with repeated lower doses.

In another dog study, 60 mg phenylhydrazine/kg body weight was administered daily to three dogs for 5 days (Allen & Giffin, 1928). One animal was moribund at sacrifice on the fifth day and one animal died on the fifth day, although it is not specified that death was treatment related. Full necropsy was performed on only one animal, in which it was found that the blood was brown and did not coagulate readily. Several organs, including the liver and kidneys, were darkly coloured, and several organs contained capillaries engorged with blood. Blood pigment and partially destroyed erythrocytes were found in the spleen. Hepatic cell atrophy was noted, and there was an increase in the iron content of the liver. Similar liver effects were seen in the two other dogs.

Bolton (1935) briefly reported the effect of repeated oral administration of 14 mg phenylhydrazine hydrochloride/ kg body weight to one dog on 4 consecutive days. There was a reduction in erythrocyte count and haemoglobin concentration, whereas white cell count gradually increased. These parameters had returned towards pretreatment values 12 days after the last dose. Pathological findings were reported to be non conclusive.

Overall, the frequency, duration, and level of exposure often varied throughout the studies reported above, so that interpretation of results is difficult. In all studies, phenylhydrazine as phenylhydrazine hydrochloride was administered either by stomach tube or by subcutaneous injection. The authors report that similar findings were obtained regardless of route. There were no control animals. None of the treated animals showed clinical signs of toxicity, and there was no excessive weight loss or gain reported. There were a number of studies available that investigate the effect of short-term repeated parenteral administration of phenylhydrazine (Bodansky, 1923; von Oettingen & Deichmann-Gruebler, 1936; Säterborg, 1974; Ades & Cascarano, 1979; Jain & Hochstein, 1979; Goldstein et al., 1980; Nishida et al., 1982; Dornfest et al.,1986). These studies confirm the ability of phenylhydrazine to damage red blood cells but otherwise do not provide any other information in relation to the toxicity of phenylhydrazine administered by occupationally relevant routes of exposure.

Human data:

No data available.

Justification for classification or non-classification

Based on the results of repeated toxicity testing, phenylhydrazine was not classified according to Regulation 1272/2008/EC (CLP) and Directive 67/548/EC (DSD).