Maleic acid dimethylester: evaluation of dermal toxicity and genotoxicity.
Maleic acid dimethylester (MAD) was investigated in acute and subacute dermal toxicity studies, for sensitization potential, and for in vivo and in vitro genotoxicity. The acute dermal toxicity in rats was low (LD50 greater than 2000 mg/kg body weight). Only local effects, erythema and necrosis, occurred at the site of application. Corresponding dose-related effects were observed in a 28-day repeated dermal toxicity study in rats. Treatment-related systemic alterations were observed in feed consumption, body weights, haematology and clinical chemistry at 170 and 500 mg MAD/kg body weight. Based on the results of this study, the no-toxic-effect level of MAD was considered to be 60 mg/kg body weight/day. However, slight dermal irritative effects were also present at the lowest dose level (60 mg/kg body weight). The primary skin irritation test in rabbits showed only slight erythema and oedema. The results of the maximization test in guinea-pigs indicated a clear sensitizing potential of MAD. In the Ames test, with five strains of Salmonella typhimurium, MAD was not mutagenic up to the highest dose level of 5000 micrograms/plate. In the micronucleus test, in which mice were given 1000 mg MAD/kg body weight by gavage the compound revealed no clastogenic effects.
Heimann
K G
KG
Berufsgenossenschaft der chemischen Industrie, Heidelberg, Germany.
Jung
R
R
Kieczka
H
H
D000279:Administration, Cutaneous; D000818:Animals; D004890:Erythema / Q000139:chemically induced*; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D008298:Maleates / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects*
D008298:Maleates; C004780:dimethyl maleate