Benzaldehyde

Endpoint summary

Additional information

Numerous studies on the repeated-dose toxicity of benzaldehyde are mentioned in the German MAK report on benzaldehyde (1998). In the following, only the most relevant studies for hazard assessment are presented.

Inhalation

In a short-term inhalation study, groups of 14 Sprague-Dawley rats per sex and group were exposed in whole anirnal exposure chambers on 14 consecutive days, for 6 hours a day, to benzaldehyde vapour in concentrations of 0, 500, 750 and 1000 mL/m3 (about 2200, 3300 and 4400 mg/m3). During the experiment 11 animals from the 1000 mL/m3 group died (10 females, 1 male) and 3 female animals from the 750 mL/m3 group. In all animals exposed to benzaldehyde, tremor, piloerection, diuresis, decreased respiration rates, hypothennia, reduced motor activity and concentration-dependent symptoms of eye and nose irritation occurred in the first week of the experiment. Body weight gains were significantly reduced in all male animals. In the animals of the 1000 mL/m3 group there were severe effects on the central nervaus system, characterised by abnormal posture and frequent seizures. In all dose groups the aspartate-aminotransferase activity in the serum was increased. Only in the female animals were the cholinesterase activity and the alburnin and total protein levels decreased, and the monocyte count and liver weights increased. In the male animals of the 1 000 mL/m3 group the haemoglobin levels, the packed cell volume, the MCH (mean absolute haemoglobin coefficient) and MCHC (mean haemoglobin concentration of the individual erythrocytes) were decreased, and in the female animals the erythrocyte count. The leukocyte count was increased in the male animals of this group. Histopathological examination revealed in the 500 and 1000 mL/m 3 groups slight (male animals) to minimal (female animals) goblet cell metaplasia, mainly in the region of the nasal septa. Inflammatory or degenerative changes in the nasal mucosa and changes in other argans and tissues were not detected. Because effects occurred even at the lowest benzaldehyde concentration of 500 mL/m3, this study did not yield a NOEL (Laham et al. 1991). In albino rats exposed over a period of 4 months for 5 hours a day to benzaldehyde concentrations of 26 mglm3 (about 6.0 mL/m3 ) under dynamic conditions, 3 months after the beginning of the experiment changes were detected in haematological parameters (hypoglobulinaemia, erythrocytosis, leukocytosis, initiallymphocytosis followed by lymphopenia) and delays in body weight gain. At the end of the experiment all the parameters were within the normal range. Exposure to benzaldehyde concentrations of 6 mg/m3 (about 1.4 mL/m3) under otherwise identical conditions was tolerated by albino rats without symptoms (no further details) (Peresedov 1974). Because of the only very incomplete description of the experiment and results, this study can be validated only in part and is not suitab\e for evaluating a MAK value.

Oral

Groups of 10 male and 10 female F344 rats were given gavage doses of benzaldehyde of 50, 100, 200, 400 and 800 mg/kg body weight (dissolved in corn oil) on 5 days/week for a period of 13 weeks. The symptoms of intoxication observed in the animals of the 800 mg/kg group were increased activity, trembling or periodic inactivity. 6 males and 3 females of this group and 1 female animal of the 400 mg/kg group and the control group died in the second half of the experiment. In the male animals of the 800 mg/kg group, body weight gains and the absolute and relative weights (relative to the brain weight) of the thymus and testes were reduced. The female animals of this group were found to have slightly increased liver, kidney, thymus and heart weights. At the end of the experiment the body weights of the male animals of the 800 mg/kg group were reduced by 26 % relative to those of the vehicle controls. In the histopathological examination, damage to the kidneys (weak to moderate degeneration and regeneration of the epithelium in the region of the proximal tubule convolution) and the brain (minimal to marked focal to multifocal degeneration and necrosis of the granular cells and Purkin cells in the cerebellum, and necrosis in the hippocarnpus) were found only in the animals of the 800 mg/kg group. In most of the animals of the 800 mg/kg group and 2 males of the 400 mg/kg group, slight hyperplasia and hyperkeratosis of the forestarnach epithelium, accompanied by increased mitotic activity in the basement membrane, were detected. For the other dose groups gross pathological and microscopic examinations were not carried out. This study therefore yielded a NOEL for female rats of 400 mg/kg body weight and day and for male rats, as a result of the slight darnage to the forestomach, of 200 mg/kg body weight and day (Kluwe et al. 1983, NTP 1990). A study with the same design was also carried out with male and female B6C3F1 mice given benzaldehyde doses of 75, 150, 300, 600 or 1200 mg/kg body weight and day. No clinical symptoms of intoxication were observed. All male animals and one female from the 1200 mg/kg group died during the first 4 weeks of the experiment. The body weight gains were reduced in the female animals after doses of 1200 mg/kg and in the male animals after doses as low as 600 mg/kg. At the end of the experiment the body weights of the male animals of the 600 mg/kg group were reduced by 9 % relative to those of the controls. The organ weights did not differ from the control values. In the gross pathological and microscopic examinations, weak to moderate degeneration of the renal tubules was detected in all male animals of the 1200 mg/kg group and one male of the 600 mg/kg group. This study therefore yielded a NOEL for male mice of 300 mg/kg body weight and day and for female mice of 600 mg/kg body weight and day (Kluwe et a/. 1983, NTP 1990).

Justification for classification or non-classification

Based on the above given information and the derived (no) effect levels, classification of benzaldehyde for repeated-dose-toxicity is not warranted, according to Regulation (EU) 1272/2008 and Directive 67/548/EEC, respectively.