Dimethyl sulphate

Carcinogenicity

Justification for classification or non-classification

IARC concluded that DMS produces mainly local tumours in rats following inhalation or subcutaneous injection and that there is sufficient evidence to classify DMS as an animal carcinogen. Given the results of the mutagenicity studies, it is assumed that DMS acts via a genotoxic mechanism.

Hence, it could be stated that due to the study published by Schlögel et al (1972), which was used as weight of evidence DMS should be classified as "Carc. 1B"; H350: May cause cancer via inhalation.

Additional information

Oral:

No data on carcinogenic properties of DMS after oral administration are reported.

Dermal:

Dermal application of 0.1 mg DMS in 0.1 ml acetone 3 times per week for a period of 385 or 475 days in ICR/Ha Swiss mice (n=20) did not lead to papillomas or carcinomas. Even when DMS was combined with the tumour promotor phorbol myristate acetate (2.5 μg/0.1 ml acetone (n=20)) the number of papillomas and carcinomas did not exceed that in controls. The number of animals in these studies was limited and only one dose was tested. No findings on non-neoplastic changes were reported. The study cannot be evaluated with regard to carcinogenic potential of DMS after dermal exposure and was rated with RL3 but will be used for weight of evidence.

Inhalation (according to the EU risk assessment report, 2002):

Male and female rats (Wistar) and mice (NMRI) were exposed to 2.6 mg/m3 DMS (6 hr/d, 2d/wk), to 10.5 mg/m3 (6hr/d, 1d/2wk), or to a sublethal concentration (4 times per year for 1 hour, 175 mg/m3 (rats) for about 15 months (Schlögel, 1972). Animals were observed for at least 30 months after start of exposure. Examinations included clinical signs, mortality, body weights, lung weights, macroscopy and histopathology. Histopathological examination was restricted to lungs and trachea. When gross examination revealed a tumour in other tissues/organs, this tissue/organ was included for histopathological examination.

DMS exposure resulted in an increased incidence of malignant tumours in the respiratory tract (nose and lungs). Rats were most sensitive to the tumour inducing activity of DMS. In all two animal species, females appeared more sensitive than males. In female rats of the 10.5 mg/m3 group, the incidence of lung adenomas was slightly higher than in control females. There were no indications that DMS exposure induced an increase in subcutaneous fibromas. The highest incidence of animals with treatment-related malignant respiratory tract tumours was found in rats exposed to 10.5 mg/m3 group. The incidence in the 2.6 mg/m3 group was distinctly lower although the total dose in the low dose group was comparable or higher than that in the 10.5 mg/m3 group. This lower incidence might be related to the lower mean survival time in the 2.6 mg/m3 group, which in its turn may be a consequence of the initially high exposure scheme applied to this group. Exposure to the sublethal DMS concentrations induced treatment-related tumours in rats only. In this context it must be realised that the exposure scheme applied for the sublethal concentrations leads to a lower total dose than that used with the 2.6 and 10.5 mg/m3 groups. Moreover, most animals of the sublethal groups have been exposed four times only. The study design does not fulfill to the requirements of OECD 451. However, the results of this study can be used to give an indication on the carcinogenic potential of DMS.