| Front page | | Contents | | Previous | | Next |

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

139     Animal toxicity

139.1     Single dose toxicity

139.1.1     Inhalation

RTECS has reported a lowest lethal concentration (LC_Lo) of 1000 ppm (equivalent to 4830 mg/m³) in rats exposed for 4 hours (NTIS –quoted from RTECS 2001).

A saturated vapour concentration (approximately equivalent to 6165 mg/m³) was tolerated by rats for 8 hours without mortalities (Smyth Jr. and Carpenter 1948).

A concentration of 2100 ppm (equivalent to 10143 mg/m³) in rats, mice, rabbits and cats first caused excitability, then somnolence. In rabbits, injury of the kidney was reported. No further details are given in the reference. (Von Oettingen 1943).

139.1.2     Oral intake

LD₅₀-values of 4000 mg/kg b.w. (Smyth Jr. and Carpenter 1948) and 2520 mg/kg b.w. (RTECS 2001) in rats, and an LD₅₀-value of 3950 mg/kg b.w. in mice (Union Carbide 1956 – quoted from A&H 1989, IUCLID 2000 and RTECS 2001) have been reported for HMP.

A single gavage dose of 2 ml HMP/kg b.w. (equivalent to 1.86 g/kg b.w.) was administered to 20 rats. Four rats were used as controls. The treatment resulted in decreased haemoglobin and RBC count (approximately 75% of values before treatment), both returning to normal 6 days later. Liver effects including increase in numbers of histiocytes, cloudy swelling, vacuolisation and granulation of the liver cell cytoplasm were also recorded. The effects peaked at 24 hours and were reversible from one week after treatment. No damage was seen at day 35. (Keith 1932).

Four rabbits administered a single gavage dose of 2.4, 4 or 5 ml HMP/kg b.w. (equivalent to 2.2, 3.7 or 4.7 g/kg b.w.) had marked respiratory depression and narcosis. The two rabbits at the top dose died, while the two other animals recovered within 24 and 48 hours, respectively. (Walton et al. 1928).

Keith (1932) reported the maximum tolerated single dose of HMP in rabbits to be of 3 ml/kg b.w. (equivalent 2.79 g/kg b.w.).

139.1.3     Dermal contact

An LD50-value of 14.5 ml/kg b.w. (equivalent to 13750 mg/kg) was reported in rabbits (Smyth Jr. and Carpenter 1948).

139.1.4     Irritation

Exposure to 2100 ppm (equivalent to 10143 mg/m³) HMP was irritating to mucous membranes in rats, mice, rabbits and cats (Von Oettingen 1943).

In an eye irritation test in rabbits, 0.005 ml or 0.02 ml HMP (equivalent to 4.65 mg or 18.6 mg) was applied to the centre of the cornea and examined 24 hours later. The irritation was evaluated to be severe and graded 5 on a 10 grade scale. (Carpenter & Smyth Jr. 1946).

In another eye irritation test using three rabbits performed according to OECD/EU guideline, HMP was reported to be mildly irritating with mean scores of 1.6, 2.0, 0.7 and 1.3 for chemosis and redness of the conjunctiva, iritis and corneal damage, respectively (IUCLID 2000).

Open application of 500 mg of undiluted HMP to rabbit skin produced mild irritation (unpublished data from Shell and Union Carbide 1959 – quoted from IUCLID 2000, RTECS 2001 and Patty’s 1982).

RTECS has reported skin irritation in rabbits following a 24-hour open application of 10 mg HMP (RTECS 2001).

139.1.5     Sensitisation

No data were found.

139.2     Repeated dose toxicity

139.2.1     Inhalation

Groups of 12 female and 12 male Wistar rats were exposed to 0, 50, 225 or 1000 ppm HMP 6 hours/day, 5 days/week for 6 weeks (equivalent to 242, 1087 or 4830 mg/m³). There was no mortality. In the high dose group, slight lethargy during and after exposure, reduction in female body weight gains at week 6 and increased liver and kidney weights were reported. Males of the high dose group had histological changes in the proximal kidney tubules (no details on the type of changes is reported). Animals of the mid dose group had increased liver weights while no effects were reported in the low dose group. (Unpublished study by Shell, 1979 - quoted from IUCLID 2000).

139.2.2     Oral intake

Oral administration to 4 rabbits of 2 ml HMP/day (equivalent to 1.86 g) for 12 days produced narcosis, kidney damage and death of three rabbits (Flury et al 1938 – quoted from Patty’s 1982).

In a range finding test over 30 days, groups of 5 males and 5 female rats were administered 0, 10, 40 and 130 mg HMP/kg b.w. in the drinking water. There was no effect on survival, growth (body weight gain) or water consumption at any dose. Histopathological effects on the liver, the kidney, the spleen and/or the testes were reported at 40 mg/kg. No details on the organ or organs involved or the type of histopathological effects found, and the no report of findings at the high dose were given in the reference. The low dose was reported not to cause any effects. (Smyth Jr. & Carpenter 1948).

139.2.3     Dermal contact

No data were found.

139.3     Toxicity to reproduction

No information was found.

139.4     Mutagenic and genotoxic effects

139.4.1     In vitro studies

HMP was tested in Ames test using the plate incorporation assay in Salmonella typhimurium strains TA 1535, TA1537, TA1538, TA98 and TA100. A reverse mutation assay with Escherichia coli WP₂ and WP₂ uvr A, was also performed. Both assays were conducted with and without metabolic activation with 10% S9 mix. The concentrations tested were up to 4000 mg/plate. Reproducibility was secured by triplicating the assay. No reverse gene mutation was induced in either bacteria. (Brooks et al. 1988).

In a yeast mitotic recombination assay, HMP suspensions at concentrations of 0.01, 0.1, 0.5, 1.0 or 5.0 mg/ml was added to a Saccharomyces cerevisiae JD1 suspension containing 10 x 10⁶ cells/ml with or without S9 mix. No mitotic gene conversion was recorded. (Brooks et al. 1988).

A chromosome aberration assay in rat liver RL₄-cells (epithelial- type cell line) was conducted with HMP concentrations of 750, 1500 2000, 3000 and 4000 mg/ml. No S9 mix was used as these cells are metabolically competent. Small increases in chromatid damage, breaks and acentric fragments were seen at 2000 and 4000 mg/ml but no clastogenic effects were observed at 3000 mg/ml. There was a slight, but not dose-related genotoxic effect of HMP. (Brooks et al. 1988).

HMP has been reported to reduce the number of mutants caused by [6]-gingerol (Nkamura and Yamamoto 1983 – quoted from A&H 1989).

139.4.2     In vivo studies

No studies were found.

139.5     Carcinogenic effects

No information was found.

| Front page | | Contents | | Previous | | Next | | Top |