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

141     Summary

141.1     Description

4-Hydroxy-4-methyl-2-pentanone (HMP) is a colourless liquid organic solvent with a sweetish odour. It is soluble in water and organic solvents, and moderately volatile.

141.2     Toxicokinetics

It appears from toxicological data, that HMP is absorbed both by inhalation and by oral intake. Intraperitoneal administration of HMP to mice resulted in similar levels in the blood and the brain. The substance is expected to be eliminated in urine as conjugates, to enter the intermediary metabolism, or to be incorporated in the tissues.

141.3     Human toxicity

HMP was found to be irritating to eyes, nose and throat following exposure to concentrations from 483 mg/m³ for 15 minutes. At this level, the odour was also objectionable.

A case study has reported glomerulonephritis following exposure over three days to paint containing HMP and ethanol.

Repeated exposure to high concentrations HMP has been reported to be defatting to the skin; however, no details are available.

No information was found on toxicity to reproduction, mutagenic and genotoxic effects, or carcinogenic effects of HMP.

141.4     Animal toxicity

141.4.1     Single dose toxicity

An LC_LO of 4830 mg/m³ over 4 hours was reported in rats. A saturated vapour concentration was tolerated by rats for 8 hours. No deaths were reported following acute inhalation exposure of rats, mice, rabbits or cats up to concentrations of 10143 mg/m³, which is higher than the saturated vapour concentration. However, no details were available in any of these reports.

Oral LD₅₀-values were reported to be 2520 or 4000 mg/kg b.w. in rats and 3950 mg/kg b.w. in mice. In rats, a sub-lethal dose of 1860 mg/kg b.w. was reported to cause decrease in haemoglobin and RBC count, and liver cell vacuolisation and granulation. In rabbits, an oral dose of 4.7 g/kg b.w. was lethal, while 2.2 and 3.7 mg/kg b.w. caused respiratory depression and narcosis.

A dermal LD₅₀-value in rabbits of 13750 mg/kg b.w. was reported.

HMP was reported to be irritating to the mucous membranes in rats, mice, rabbits and cats at concentrations of 10143 mg/m³. Eye irritation reports are conflicting as HMP was reported to cause severe irritation in an elder range-finding test but only mild irritation in another test, conducted according to OECD/EU guideline.

HMP has been reported to be a mild irritant to rabbits skin in one reference and to be skin irritating in another.

No data were available on the sensitising potential of the substance.

141.4.2     Repeated dose toxicity

Inhalation exposure of rats from 242 to 4830 mg/m³ HMP (HMP) for 6 weeks resulted in slight lethargy, increased liver and kidney weights, and unspecified histological changes in the proximal renal tubules of male rats at the high dose, while only liver weights increase was reported at the mid dose and no effects were seen at the low dose.

Rats exposed to 40 mg HMP/kg b.w. in the drinking water for 30 days were reported to have histopathological changes in either the liver, the kidney, the spleen or the testes, while 10 mg/kg did not induce any changes.

141.4.3     Toxicity to reproduction

No information was found.

141.4.4     Mutagenic and genotoxic effects

HMP was negative in reverse mutation assays in Salmonella typhimurium and Escherichia coli strains with and without metabolic activation and did not induce mitotic gene conversion in a yeast recombination assay.

A slight increase in chromatid damage, breaks and fragments was seen in a chromosome aberration test in rat liver cells in vitro, but no dose-response relationship was established; HMP was concluded by the authors to be slightly clastogenic.

No in vivo data were found.

141.4.5     Carcinogenic effects

No information was found.

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