Acute and Subchronic Repeated Cutaneous Application of N-Methyldiethanolamine in the Fischer 344 Rat

The potential for local and systemic toxicity by recurrent contamination of the skin with N-methyldiethanolamine (MDEA; CAS No. 105-59-9) was investigated in the Fischer 344 rat. Two short-term repeated studies (9 days, 6 h/day) and one subchronic (65 applications over 13 weeks) were conducted with monitoring for clinical signs, body weight, food and water consumption, hematologic findings, clinical chemistry, urinalysis, gross and microscopic pathology analysis. The first 9 day study with undiluted MDEA (260, 1040, and 2080 mg/kg/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/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/day), 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.