Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

110 Evaluation

The toxicological database on dipropylene glycol monomethyl ether (DPGME) is limited. However, the substance is evaluated from the available data to be of low toxicity, the critical effect being eye and mucous membrane irritation.

Commercial DPGME is a mixture of isomers which only contains small amounts of primary alcohols, which are potentially capable of forming the teratogenic metabolite methoxypropionic acid, MPA. The secondary alcohol isomers are metabolised via dealkylation to carbon dioxide. Metabolism studies on DPGME have not identified MPA in rat urine. The potential of commercial DPGME for causing adverse effect on development is therefore considered to be negligible.

DPGME is of very low acute toxicity to rodents and dogs by inhalation (>3080 mg/m³), oral (5130-7500 mg/kg b.w.), and dermal (9-19 mg/kg b.w.) exposure. Non-specific CNS depression was seen at sub-lethal doses in rodents.

The substance is a moderate irritant to mucous membranes in humans and in animals. Reversible conjunctivitis and keratitis as well as increase in the intraoccular tension have been reported in humans and in rabbits. DPGME is not a skin irritant in animals or humans. No signs of sensitisation of humans have been reported.

Bone marrow depression has been reported from human exposure to DPGME in a dermal and inhalation exposure with concurrent exposure to other solvents. The finding was not confirmed in a subchronic dermal study in rabbits with exposure levels up to 9400 mg/kg b.w. DPGME. On this background, DPGME is evaluated not to have effect on bone marrow. Subchronic inhalation exposure of rats to the maximum obtainable vapour concentration of DPGME of 1848 mg/m³ resulted in transient CNS depression. Slight central area cytoplasm granulation and non-fatty vacuolation of the liver was reported in rabbits, guinea pigs and monkeys treated at 1848 mg/m³for 6-8 months. No liver effects were seen in other subchronic inhalation studies in rats and rabbits with exposure levels of up to 1232 mg/m³ DPGME.

No specific studies on fertility effects were found; however, subchronic studies in rodents reported no effect on testes by inhalation to 1232 mg/m³ or dermal exposure to 1000 mg/kg b.w. Teratogenicity studies in rats and rabbits showed no treatment related developmental toxicity at up to 1756 mg/m³.

DPGME was negative in in vitro genotoxicity tests, but has not been tested in vivo for mutagenicity. The subchronic studies indicate no specific concern for a carcinogenic potential of the substance. However, this effect cannot be evaluated conclusively, as no studies were found on carcinogenicity.

In conclusion, the dipropylene glycol monomethyl ether is found to have a low toxicity, the critical effect being irritation of the eye and the mucous membranes.