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Key value for chemical safety assessment

Justification for classification or non-classification

The test substance is classified according to Annex I of the Directive 67/548/EEC with Carc. Cat. 3, R 40.

Additional information

NTP (1988) reported a toxicity and carcinogenity study using male and female rats. Vapour concentrations (whole body exposure) used were 200 and 400 ppm. The study duration was 103 weeks; the frequency of treatment was 6 hours per day and 5 days per week. With respect to the benign nasal tumours observed in this study, these showed no sign of progression to malignancy and must be seen against the background of extensive non-neoplastic lesions at this dose level (400 ppm). These tumours are likely to be a direct consequence of the irritant properties of 1,2-epoxybutane leading to stimulation of cell proliferation. It is, therefore, highly unlikely that these tumours occur at dose levels which do not produce chronic tissue irritation. A small but statistically significant incidence of lung tumours (carcinomas and adenomas combined) was confined to the male rat and to the top dose level of 400 ppm. These tumours occurred late in the study and showed no evidence of metastasis. The increase in malignant lung tumours alone was not statistically significant. It required the combination of benign and malignant tumours to obtain the statistical significance to enable NTP to classify 1,2-epoxybutane as "clear evidence of carcinogenic activity". Furthermore, one could question whether a practical maximum Tolerated Dose was exceeded in the NTP study in view of the significant upper respiratory tract irritation. NTP categorized the results obtained with female rats as "equivocal evidence of carcinogenic activity", demonstrated by studies that are interpreted as showing a marginal increase of neoplasms that may be chemically related. Two high dose (400 ppm) females developed benign nasal cavity tumours and 1 female developed a benign alveolar/bronchiolar tumour. on the other hand, one female control developed a malignant alveolar/bronciolar tumour. On this basis it is highly questionable as to whether or not the treated females could be considered to "show a marginal increase of neoplasms that may be chemically related".

Male and female mice did not show tumours in any organ at either dose level in a 102-week inhalation vapour study (whole body). Concentrations used were 50 and 100 ppm; study duration: 102 weeks; frequency of treatment: 6 hours per day, 5 days per week (NTP, 1988).