Dimethyl sulphate

Endpoint summary

Additional information

All studies available for repeated dose toxicity are considered to be of low reliability (RL 3 or RL 4), and no NOAEL could be derived. However, a short communation of citations found and evaluated during the literature search is made available in section 13 of this technical dossier.

According to the EU risk assessment, 2002 the following on repeated dose toxicity, inhalation is stated:

In a carcinogenicity study, rats and mice were exposed to 2.6 mg/m3 DMS (6 hr/d, 2d/wk) or 10.5 mg/m3 (once every two weeks) or a sublethal dose of 175.35 mg/m3 (every 3 months) for about 15 months (Schlögel, 1972: see 7.5.3). It is considered not suitable for evaluation as repeated dose study according to the guidelines, because no haematology, no clinical biochemistry and very limited histopathological examinations were performed.

After exposure, the behaviour of exposed animals was affected: animals were apathic, eyes were half-open or closed and breathing problems were apparent. These effects clearly showed a concentration dependency in severity, total duration and time of onset. Body weight gain in DMS-exposed rats and mice was distinctly lower than in control animals. In general, survival in groups exposed to DMS was lower than in controls, but the mean survival time varied considerably between the various groups. A remarkable finding was the very low survival time in male and female rats of the 2.6 mg/m3 group which was distinctly lower than the survival time in rats of the control or the 10.5 mg/m3 group. The same phenomenon was seen in mice although less pronounced. The lower survival time in the 2.6 mg/m3 group is probably due to the initial high exposure regimen applied to this exposure group. An increase in the incidence of inflammation of the lungs was reported in DMS-exposed animals in all species. Bronchiopneumonia occurred to about the same degree in control and DMS exposed animals.

Justification for classification or non-classification

The available data are considered as insufficient to derive a NOAEL for repeated exposure. Amongst others the study of Schlögel is considered not suitable for evaluation as repeated dose study according to the guidelines, because no haematology, no clinical biochemistry and very limited histopathological examinations were performed. The data submitted do not fulfil the basic requirements for classification and labelling of the substance in accordance to regulation (EC) 1272/2008. However, according to the EU risk assessment report, 2002 it is noted that the carcinogenic activity of DMS, i.e., the cancer incidence per mg/m3 under occupational conditions of exposure, points to very low acceptable exposure levels with regard to the carcinogenic effects. It is expected that compliance to these low exposure levels will prevent effects other than carcinogenic effects to occur.

Since the substance fulfills the requirements under regulation (EC) 1907/2006 article 18(4) a-f it is not foreseen to initiate a further repeated dose toxicity study.