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

94     Evaluation

Most of the available toxicological data on 1-methoxy-2-propanol (2PG1ME) relate to the commercial compound methoxy-propanol (PGME), which consists of 95-99% 2PG1ME and less than 5% 2-methoxy-1-propanol (1PG2ME). On the basis of these data, it appears that 2PG1ME is of low systemic toxicity; irritation of the eyes, the mucous membranes and the respiratory tract as the critical effects. The substance is also a CNS-depressant.

2PG1ME appears to be absorbed by all routes of exposure. It is primarily metabolised via demethylation and oxidised to CO2, a minor part being excreted through the urine in conjugated form. The toxic metabolite methoxyacetic acid is not formed by 2PG1ME, but only by its  b-isomer 2PG1ME.

PGME is of low acute toxicity. No poisoning cases in humans were found. LC50-values in animals were approximately 54600 mg/m3 following 4 hours exposure in rats and10 hour exposure in  Guinea pigs, and higher in rabbits and monkeys. Oral LD50-values of 5000-10800 mg/kg b.w. were reported for rats, mice, rabbits and dogs. The dermal LD50 –value for rabbits was around 13000 mg/kg b.w.

PGME caused dizziness and headache in human volunteers from 1125 mg/m3, and one case of loss of ability to balance is reported at 3750 mg/m3.

CNS-depression was also the major symptom reported from acute studies in rats, mice, Guinea pigs, rabbits and monkeys from 25500 mg/m3. Oral and dermal exposure at sublethal doses also resulted in CNS depression in rats, rabbits and dogs.

In humans. The substance was irritating to the eyes, nose and throat at 938 mg/m3.

In animals, the substance was reported to be irritating to the respiratory tract of rats from 37500 mg/m3. PGME was not irritating or mildly irritating to the eyes of rabbits. No information on skin irritation in humans were available, and no or slight irritation occurred in rabbits following exposure to PGME. The substance was not sensitising in Guinea pigs.

No human data were available on effects of repeated exposure to PGME.

Animal data showed increased liver weights, hypertrophy of the liver and occasional slight non-fatty degeneration and granulation of the liver of rats, mice, guinea pigs, rabbits following repeated exposure to 5450 to 21800 mg/m3up to 6 months. In a two-year inhalation study in rats and exposed to 1125-11250 mg/m3, the liver weights and the incidence of eosinophilic hepatocellular foci were increased in the high dose animals.

Development of glomerulonephritis was significantly increased in male rats exposed to 11250 mg/m3 over 24 months compared to controls. There was no increase in tumour incidence. No increase was seen in females. The mechanism of nephrotoxicity in males was probably related to the measured increased levels of a2u-globulin, which is specific to male F344-rats and considered not to be a relevant mechanism for humans.

No effect on testis resulted from inhalation exposure of rats up to 2250 mg/m3 PGME or oral exposure of mice to 2.5 g/kg b.w.. Dogs treated orally with 462 mg/kg b.w. had macrophages in the testes and epididymis. The finding was so scarcely described in the reference that it cannot be evaluated. However, as no similar pathological change were found in any other study, it is not considered to be toxicologically significant.

No foetotoxicity was seen from exposure by gavage of mice or rabbits during gestation at doses of 1848, respective 924 mg/kg b.w. Delayed ossification of the sternebrae and the skull occurred in pups of rats dosed 11250 mg/m3 by inhalation and orally to 739 mg/kg b.w., respectively. Maternal toxicity was seen in rabbits and rats at these levels. In a continuous breeding study in mice where PGME was given in the drinking water, reduced birth weights, epididymis and prostate weights were seen at 3.3 g/kg b.w. PGME while no effects were seen in the dams. On this basis, PGME is considered not to have any adverse effect on fertility or to cause developmental toxicity.

 

PGME was negative in three different in vitro mutagenicity tests. No in vivo tests were available.

No increased incidence of tumours was found in a 2-year inhalation study in rats and mice exposed up to 11250 mg/m3.

In conclusion, 2PG1ME is considered to be of low systemic toxicity and its critical effects  being irritative effects to the eyes, the mucous membranes and the respiratory tract and depression of the central nervous system.

 

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