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

21   Summary

21.1   Description

Dimethyl ether (DME) is a colourless gas at room temperature and with a slight ethereal odour. The substance has a very high vapour pressure, and is soluble in water.

21.2   Toxicokinetics

DME is rapidly taken up after inhalation and distributed to various organs and tissues, where a steady state level is reached within 30 minutes. After end of exposure, the concentration of DME in organs and tissues falls very rapidly again.
The elimination is described as a two-phase process. No tissue storage is seen.No data on absorption, distribution or elimination of DME after oral intake or dermal contact were found.

21.3   Human toxicity

The only effects described after DME exposure to humans originate from very old studies, where human subjects have been exposed to very high acute doses of DME. The target organ after exposure to high concentrations of DME is the central nervous system, covering effects from incoordination, indistinct vision, and inability to do simple tasks and to unconsciousness (exposure levels from 75000 to 200000 ppm - 143000 to 382000 mg/m³).

No information on toxic effects in humans following repeated dose exposure was found. Likewise no information on reproductive or developmental effects, as well as on mutagenic, genotoxic or carcinogenic effects in humans was found.

21.4   Animal toxicity

21.4.1   Single dose toxicity

The LC₅₀-values for DME in mice have been reported to be 490000 ppm (936000 mg/m³) after exposure in 15 minutes and 380000 ppm (726000 mg/m³) after exposure in 30 minutes.
In rats, the LC₅₀-value has been reported to be 164000 ppm (313000 mg/m³) after 4 hours exposure. The effects of DME in rats exposed to sub-lethal doses range from sedation to narcosis.
In dogs exposed to 200000 and 300000 ppm (382000 and 573000 mg/m³), DME has been reported to be a light cardiac sensitiser.

21.4.2   Repeated dose toxicity

Short-term studies (2 weeks) in which rats were exposed to concentrations of DME of 50000 ppm (96000 mg/m³) caused sedation, body weight gain suppression, haematology and organ weight changes, but no histopathological organ changes. All changes were completely reversed after cessation of exposure.In sub-chronic studies (13 or 30 weeks) with exposure of DME up to 20000 ppm (38000 mg/m³) in rats and hamsters, the reported effects focus on changes in haematological parameters (white blood cells) for both rats and hamsters, and an increase of serum SGPT and SGOT values in rats, the last suggesting a possible onset of a hepatotoxic effect of DME. By histopathological examinations, no effects were observed in the liver.
The no-effect level for haematological effects in the 13-week studies was reported to be 10000 ppm (19000 mg/m³) for rats and 5000 ppm (9600 mg/m³) for hamsters. In the 30-week study on rats, the no-effect level for increased levels of SGPT was reported to be 2000 ppm (3800 mg/m³) and for increased levels of SGOT 200 ppm (380 mg/m³).

In a lifetime study in rats exposed to concentrations up to 25000 ppm (48000 mg/m³) of DME, the only effect reported was a decrease in mean survival time for female rats from 10000 ppm (19000 mg/m³) . The decrease was not statistically significant, but different from that seen in the low dose group (2000 ppm - 3800 mg/m³) and the control group. The no-effect level was reported to be 20000 ppm (38000 mg/m³).

21.4.3   Toxicity to reproduction

In a developmental study, female rats were exposed to concentrations of 20000 or 28000 ppm (38000 or 53000 mg/m³) of DME from days 6 to 15 of gestation. The researchers found a statistically significant increase in the number of extra ribs in the foetuses at both dose levels, these findings was not accompanied by maternal toxicity at any of the dose groups. There were no signs of teratogenicity or embryo mortality.

In another developmental study, with exposures of 0, 1250, 5000, 20000, or 40000 ppm (0, 2400, 9600, 38000, or 76000 mg/m³), to female rats from day 6 to 15 of gestation, the female animals showed evidence of narcotic effect from 5000 ppm (9600 mg/m³) and suppressed body weight gain at 40000 ppm (76000 mg/m³). There was no evidence of teratogenic effects or increase in foetal resorptions. Retarded ossification of the rib bones and some of the phalangeal bones in the extremities of the foetuses was considered as variations reflecting developmental delay rather than a specific effect on the foetuses.

21.4.4   Mutagenic and genotoxic effects

DME showed no signs of a mutagenic or genotoxic potential in 3 in vitro and 2 in vivo test systems.

21.4.5   Carcinogenic effects

In a lifetime study in rats exposed to DME at concentrations up to 25000 ppm (48000 mg/m³), there was no increase in cancer in any of the tissues or organs of the animals. 

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