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Administrative data

Description of key information

In a sub-chronic dermal toxicity study in rats (similar to OECD guideline 411), local and systemic NOAELs of 100 mg/kg bw/day (corresponding to 0.8 mg/cm2) and 750 mg/kg bw/day were established, respectively. 

Key value for chemical safety assessment

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
750 mg/kg bw/day

Additional information

Two short-term (9 days) and one sub-chronic dermal repeated dose studies with rats were available for assessment (Werley et al, 1997).The first 9-day study with undiluted MDEA (260, 1040, and 2080 mg/kg bw/day) produced dose-related skin irritation with related hematological and clinical chemistry changes. Adrenal weights were increased, a common finding in cutaneous irritation studies, and kidney weights were increased but without urinalysis or histological evidence of renal injury. Histopathologic investigation was limited to the skin treatment area. The second 9-day study, using aqueous dilutions of MDEA (100, 500, and 750 mg/kg bw/day) showed local irritation at the mid and high doses with associated clinical chemistry changes and increased adrenal gland weight. There were slight reductions in body weight gain. There were no effects on hematology or urinalysis, and histopathologic findings were limited to the treated skin.

The subchronic study, also with aqueous dilutions (100, 250, and 750 mg/kg bw/day for 6 hours/days, 5 days/week, 13 weeks), showed dose-related irritation in the mid and high dose groups; major histopathological features were acanthosis, hyperkeratosis, parakeratosis, dermatitis, dermal fibrosis, eschar, and ulceration. Low-dose group findings were similar to the controls, and probably a consequence of the wrapping procedure. There were no effects on clinical pathological findings or organ weights, and histopathological findings were limited to treated skin. These studies show that recurrent application of MDEA produces a dose-related irritant effect, but there is no evidence for systemic cumulative or specific target organ or tissue toxicity. Based on the sub-chronic study, local and systemic NOAELs of 100 (corresponding to 0.8 mg/cm2based on an exposed body surface area of 25 cm2and an assumed body weight of 0.2 kg) and 750 mg/kg bw/day were established upon dermal exposure, respectively.

Justification for classification or non-classification

Based on the results of dermal repeated dose toxicity studies, MDEA does not need to be classified according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.