2,3-epoxypropyltrimethylammonium chloride

Carcinogenicity

Description of key information

In a two-year cancer study, EPTAC was applied on CF1 mouse skin (Kr: 2, Doak, 1983): EPTAC is a skin carcinogen, probably; it is also a systemic carcinogen. EPTAC is classified as carcinogen in the Annex VI of the CLP regulation (1272/2008/EC).

Key value for chemical safety assessment

Carcinogenicity: via dermal route

Endpoint conclusion

Dose descriptor:

BMD05

9.7 mg/kg bw/day

Justification for classification or non-classification

Harmonised classification:

EPTAC is classified as carcinogenic Cat.1B, H350 (may cause cancer) in the Annex VI, Table 3.1 of the CLP regulation (1272/2008/EC) and as carcinogenic Cat.2, R45 in the Annex VI, Table 3.2 of the CLP regulation (1272/2008/EC).

No additionnal self-classification is proposed

Additional information

Carcinogenicity: dermal

One study was available, considered as valid (Kr:2) and was used for Harmonised classification (Doak, 1983).

In a two-year cancer study, EPTAC was applied on CF1 mouse skin at concentrations 0.1, 0.3 and 1.0% (w/v) (1% was a nonirritant concentration in a pre-test). Each dose level had 50 male and 50 female mice, except the solvent (ethanol/nonident) which had 100 mice per group and sex. A concentration of 10 mg/ml beta-propiolactone was used to act as the positive control. The test and control substances were applied twice weekly, 0.2 ml at a time, and the treatment continued for up to 104 weeks. Expressed as weight the doses are 0.2, 0.6, 2.0 mg/animal/application. In the absence of data on average animal weight during the exposure (no weight records were available and there is no mention that these data was collected), we use an average weight TGD default assumption of 40 g. Using this assumption, the doses are 5, 15 and 50 mg/kg/application or 10, 30 and 100 mg/kg/week. Based on the in vitro absorption assay with mouse skin, 22.6 to 43.6 % of CHPTAC ((3-chloro-2-hydroxypropyl)trimethylammonium chloride) passed through the skin at this concentration. The clinical observations were made twice daily and detailed records of skin lesions and site were kept. In necropsy, a macroscopical examination was performed and when gross abnormalities were found the organ was sectioned for microscopical preparation. At histological examination, a distinction between malignant and benign tumours was made and the tumours were grouped as either originating from the treated site or from an untreated area.

Decreased survival time were observed especially among females. There was a statistically significant increase of skin tumours when mice where treated topically with 1 % EPTAC (~50 mg/kg/application). In females, there was also a statistically significant increase of lung tumours, mammary gland tumours, lachrymal gland tumours and reticulum cell sarcoma in the 1 % EPTAC treatment group. Of systemic tumours, a statistically significantly increased number of thymic lymphosarcoma in males of the 1 % dose group was reported. Although EPTAC is a genotoxic, the mode of action, which caused the occurrence of the systemic tumours, is somewhat unsure. While authors speculated viral interaction may have been involved, it is also unsure whether EPTAC reaches the body further than the dermis in sufficient quantities to have caused the systemic tumours. Because EPTAC is a mutagen, the mode of action of the tumour formation is presumed not to have a threshold. A BMD0.1 (5d) of 9.7 mg/kg bw (malignant and benign tumours combined) can be used in the risk characterisation.

EPTAC is classified as carcinogenic Cat1B, H350 (May cause cancer) according to the criteria of the CLP regulation (1272/2008/EC) and as carcinogenic, Cat.2, R45according to criteria of the Directive 67/548/EEC.

Carcinogenicity: oral and inhalation routes

No data was available.

Carcinogenicity: via dermal route (target organ): other: skin