| Front page | | Contents | | Previous | | Next |
Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants
109 Summary
109.1 Description
109.2 Toxicokinetics
109.3 Human toxicity
109.3.1 Single dose toxicity
109.3.2 Repeated dose toxicity
109.3.3 Toxicity to reproduction
109.3.4 Mutagenic and genotoxic effects
109.3.5 Carcinogenic effects
109.4 Animal toxicity
109.4.1 Single dose toxicity
109.4.2 Repeated dose toxicity
109.4.3 Toxicity to reproduction
109.4.4 Mutagenic and genotoxic effects
109.4.5 Carcinogenic effects
109.1 Description
Dipropylene glycol monomethyl ether (DPGME) is a colourless liquid with ether odour. It is an organic solvent with a relatively low vapour pressure of 0.37 hPa. It is completely miscible with water and a large number of organic solvents.
109.2 Toxicokinetics
DPGME is readily absorbed through all routes of exposure. The substance is a mixture of 4 isomers, two primary and two secondary alcohols. The secondary alcohols are metabolised via the P-cytochrome oxidase of the liver by O-demethylation and excreted as propylene glycol or dipropylene glycol in the urine or further oxidised to carbon dioxide. Sulphate and glucuronide conjugation also occurs. For the primary alcohols metabolism includes dehydrogenation and formation of the teratogenic metabolite methoxypropionic acid (MPA). However, only very small amounts of these isomers are present in commercial DPGME. MPA was not detected in rat urine.
109.3 Human toxicity
109.3.1 Single dose toxicity
Reversible eye irritation has been reported following application of 0.04 ml of a 20% solution of DPGME (7.5 mg). Irritation by inhalation has been reported following exposure to 456 mg/m3.
109.3.2 Repeated dose toxicity
Neither irritation nor sensitisation occurred following repeated occluded dermal exposure to DPGME.
Bone marrow depression was reported in one study following occupational exposure to DPGME in mixed exposure with a number of other solvents.
109.3.3 Toxicity to reproduction
No data were found.
109.3.4 Mutagenic and genotoxic effects
No data were found.
109.3.5 Carcinogenic effects
No data were found.
109.4 Animal toxicity
109.4.1 Single dose toxicity
Inhalation exposure of rats to a vapour and aerosol concentration of 3080 mg/m3 DPGME for 7 hours caused narcosis. Reported oral LD50-values range from 5000 to 7500 mg/kg b.w. in rodents and dogs and dermal LD50-values in rabbits range from 9.4 to over 19 g/kg b.w.
The substance is reported not to be a skin irritant following open application. Eye irritation studies in rabbits indicate that the substance is a reversible eye irritant.
109.4.2 Repeated dose toxicity
Nine days inhalation exposure of rats and mice to up to 2033 mg/m3 DPGME resulted in increased relative liver weights in male rats and female mice, but no pathological changes were found.
Rats exposed for 90 days to up to 1232 mg/m3 DPGME were not affected by treatment.
Rabbits exposed for 90 days to up to 1232 mg/m3 of the substance showed increase in relative kidney weight within the range for historic controls and without pathological findings in the organ.
Transient CNS depression was reported and the liver was affected (slight granulation of the cytoplasm in the central area and vacuolisation) in rabbits, guinea pigs and monkeys following inhalation exposure to the maximal attainable vapour concentration of 1848 mg/m3 for 6 to 8 months.
In a 28-day dermal rat study under both occluded and open application of up to 1000 mg/kg b.w./day, only non-significant effects on haematological parameters were seen. No pathological or histopathological changes were recorded in the liver or on the bone marrow.
In a 90-day dermal rabbit study with application under occluded patch of doses up to 9.4 g/kg b.w./day, the majority of the animals of the high dose group died following symptoms of narcosis and body weight loss. Haemorrhagic areas were observed in the gastric mucosa. There were no other treatment related findings in clinical chemistry or histopathology.
109.4.3 Toxicity to reproduction
No studies on fertility were found. However, a 90-day study by dermal contact in rats and rabbits with up to 1000 mg/kg b.w. and a 2-week inhalation study in rats and mice with up to 200 ppm (1232mg/m3) showed no effects on testes.
No treatment related effects on development have been reported following inhalation exposure to up to 1756 mg/m3 of rats from day 6-15, and rabbits day 7-19 of gestation. The low number of malformations observed did not exceed the number observed in the controls.
109.4.4 Mutagenic and genotoxic effects
The substance was negative with and without metabolic activation in an Ames test, a CHO-cell metaphase analysis test and a UDS test in rat hepatocytes. No in vivo studies were found.
109.4.5 Carcinogenic effects
No studies were found.
| Front page | | Contents | | Previous | | Next | | Top |
|