Dermatotoxicology of BIS[2-(Dimethylamino)Ethyl] Ether

Abstract

The potential for local and systemic toxicity from acute, short-term repeated (9-day), and subchronic (13 weeks) application of bis[2-(dimethylamino)-ethyl] ether (DMAEE) to the skin was investigated in rabbits. By single occluded and unoccluded contact, DMAEE produced severe local dermal inflammation with necrosis. Aqueous dilutions of DMAEE in a concentration range of 2.5–10% (v/v), and applied daily for 9 days, caused a concentration-related and cumulative moderate to severe local dermal inflammation. Subchronic recurrent application of more dilute solutions (0.25–1.98% v/v) also produced a concentration-related mild to moderate local dermal inflammation, which slowly subsided after cessation of treatment. The acute percutaneous LD₅₀ of undiluted DMAEE by 4-hr occluded contact was 0.41 (0.30–0.56) ml/kg in males and 0.63 (0.54–0.74) ml/kg in females; for 24 hr occlusion the LD₅₀ was 0.37 (0.25–0.55) ml/kg in males and 0.37 (0.20–0.67) ml/kg in females. A 20% (v/v) aqueous solution was determined to have an LD₅₀ of 2.14 (1.45–3.17) ml/kg in males and 2.83 (1.68–4.77) ml/kg in females by 24 hr occluded contact. Short-term repeated dermal applications of 1 ml DMAEE in the concentration range 2.5–10.0% (v/v aqueous) did not cause mortality, but produced a concentration-related decrease in food consumption and body weight, with renal tubular epithelial hydropic changes primarily affecting the collecting ducts. Subchronic dermal applications of 1 ml aqueous DMAEE in a concentration range 0.25–1.98% (v/v) produced cumulative dermal irritation, but no biochemical or histologic evidence of nephrotoxicity or other target organ or tissue toxicity. The absence of systemic toxicity by subchronic recurrent dermal application of dilute aqueous solutions of DMAEE could be related to its metabolic transformation. The relatively high potential for local and systemic toxicity from acute and short-term repeated contact with undiluted DMAEE and concentrations in water of 2.5% and higher indicates the need for skin protection when handling the material.