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2778098 
Technical Report 
Resmethrins-Resmethrin, Bioresmethrin, Cisresmethrin 
Who working group 
1989 
RISKLINE/1990010041 
92 
1989 
English 
Physical and Chemical Properties Technical grade resmethrin is a colourless waxy solid with a melting point of 43-48 �C and a boiling point of 180 �C at 0.01 mmHg. The specific gravity is 1.050 at 20 �C. The vapour pressure is 1.1 x 10-8 mmHg at 30 �C. It is insoluble in water ( and lt; 1 mg/litre at 30 �C), but soluble in organic solvents, such as hexane, kerosene, and xylene. It is not stable in air, light, or in alkaline media. The n-octanol/water partition coefficient is 2.9 x 10 3 for resmethrin and 6.2 x 10 4 for bioresmethrin. Environmental Fate Resmethrin is rapidly photodegraded on silica gel plates, as a thin film on glass plates. and in aqueous solution. In sunlight, aqueous solutions have a half-life of 47 min (pure water) and 20 min (sea water). A range of photoproducts is formed from ester cleavage and oxidation reactions. Resmethrin is also very rapidly degraded in soil. 2% of the applied parent compound remaining after 16 days. Complete mineralization to carbon dioxide is a very important degradation process (38% after 16 days). Rapid degradation occurs on plants (tomato. lettuce. and wheat). After 5 days. no resmethrin is detected on plants and a very complex mixture of. at least. 31 break-down products is formed. The alcohol formed by ester cleavage, benzaldehyde, phenylacetic acid, benzoic acid, and benzyl alcohol were identified as break-down products, each being present at low levels (3% of the total residue). Effects on Experimental Animals and In Vitro Test Systems Resmethrin and bioresmethrin were weakly toxic for animals when examined by various routes of exposure (the oral LD50 of resmethrin ranged from 690 mg/kg for the mouse to and gt;5 000 mg/kg for the rat). The oral LD50s for bioresmethrin were 225 mg/kg for the rabbit, 480-10 000 mg/kg for the mouse, and 8800 mg/kg for the rat. Cismethrin was moderately toxic for the mouse (oral LD50: 152-160 mg/kg), Signs of poisoning were tremors, hyperactivity, and convulsion (T-syndrome). Resmethrin belongs to the Type pyrethroid group. The acute toxicity (oral and intraperitoneal) of the metabolites (e.g., CA, BFA, BFCA) was examined in mice and rats; CA and BFA were more toxic than the parent compound in mice though toxic signs were different. The acute toxicity (oral LD50) of the metabolites in rats ranged from 997 mg/kg to and gt; 4640 mg/kg, which is within the same range of acute toxicity as the parent compound, While technical grade resmethrin was found to be a slight irritant to the skin, it did not cause sensitization and photochemical irritation in guinea-pigs and New Zealand White rabbits. Resmethrin was applied twice weekly, for 3 weeks, to the skin of New Zealand White rabbits by fixing a piece of cotton cloth treated with resmethrin (0.247 mg/cm2) over skin that had been pre-treated with liquid, imitating sweat, or with resmethrin (10 g), or had not been pre-treated. No significant changes were noted in body weight and organ weight ratios on day 24 or in the clinical chemistry in any of the groups up to day 24. No significant compound-related dermal effects were observed. When Sprague-Dawley or Long-Evans rats were fed resmethrin in the diet at levels of up to 6000 mg/kg for 14 days, mortality was observed at the highest dose level, and tremor and reduced body weight and food consumption were noted at levels of 1500 mg/kg or more. The maximum no-observed-adverse-effect dietary level was 188 mg/kg for Long-Evans rats. When Long-Evans rats were given resmethrin in the diet at levels of up to 750 mg/kg (male) and up to 2400 mg/kg (female) for 90 days, all females died at 2400 mg/kg and tremor and reduced body weight were noted at 750 mg/kg. The maximum noobserved-adverse-effect dietary level was 75 mg/kg for both female and male rats. When rats were fed bioresmethrin in the diet at levels of up to 8000 mg/kg for 91 days, body weight was reduced at the highest level, and was accompanied by changes in blood chemistry indicating liver dysfunction. The no-observed-adverse-effect level in this study was 400 mg/kg diet, which corresponds to 32,8 mg/kg body weight and 36,1 mg/kg body weight for males and females, respectively. Dogs (males and females) were administered bioresmethrin at levels of up to 500 mg/kg body weight for 90 days. A noobserved-adverse-effect level was observed of 80 mg/kg body weight. Technical resmethrin was administered via inhalation to Wistar rats for 6 h/day on 5 days of each week, for a period of 90 days, at nominal exposure levels of 0.1, 0.3, or 1.0 g/m3. The no-observed-adverse-effect level was at 0.1 g/m3. Rats and rabbits inhaled aerosolized resmethrin formulations for 5 h/day on 5 consecutive days at levels of 2.9-3.2 mg active ingredient/litre of air. Though clinical signs including rapid breathing and nasal discharge were observed, there were no compound-related effects on body weight and histopathological findings, immediately and 7 and 14 days after exposure. No indication of toxic effects other than irritation were observed in any of the tests. No oncogenic effects were seen when CD-1 mice were fed 0 250, 500, or 1000 mg resmethrin/kg basal diet for 85 weeks. Wistar rats fed resmethrin at levels of 0, 500, 2500, or 5000 mg/kg basal diet for 112 weeks did not show any signs of oncogenicity and a no-observed-adverse-effect level of 500 mg/kg was established for chronic toxicity. When resmethrin was administered to Sprague-Dawley rats at dietary levels of 500, 1500, or 5000 mg/kg for 24 weeks, tremors decreased body weight, and increased liver and kidney weights were observed at 5000 mg/kg. A no-observed-adverse-effect level of 1500 mg/kg was established. Dogs fed resmethrin for 6 months showed increased liver weights at 30 mg/kg body weight per day, but did not show any adverse effects at 10 mg/kg body weight per day. Resmethrin, bioresmethrin, and cismethrin were tested for mutagenicity and/or chromosomal effects in several short-term test systems, such as Escherichia coli and Salmonella reverse mutation tests, primary DNA damage tests in eukaryotes and prokaryotes, and chromosomal effects in Chinese hamster cells or mouse bone marrow cells. Negative results were obtained with all tests. In a teratogenicity study, pregnant Long-Evans rats were administered resmethrin in the diet at levels of 188 or 1500 mg/kg, from day 6 to day 16 of gestation. Though mortality, tremor, and decreased food and water consumption were noted in the dams at 1500 mg/kg, gross abnormalities of the fetal skeleton and soft tissues were not observed in the treated animals. Resmethrin was administered orally (by gavage in corn oil) at levels of 0. 20, 40, or 80 mg/kg body weight to female Sprague-Dawley rats during the period of major organogenesis. Resmethrin was not teratogenic at levels up to and including 80 mg/kg. The no-observed-adverse-effect level for fetotoxicity was 40 mg/kg. ICR mice were given (+),-[trans, cis]-resmethrin orally at levels up to 100 mg/kg body weight. Sprague-Dawley rats received levels up to 50 mg/kg body weight during the period of major organogenesis. Embryo- and fetotoxicity and teratogenicity were not observed in this study. In another study, resmethrin was administered to New Zealand White rabbits by oral intubation at dose levels of 0, 10. 30, or 100 mg/kg body weight on day 6 to day 18 of gestation. Resmethrin was not teratogenic including the 100 mg/kg dose. In a 3-generation reproduction study, Sprague-Dawley rats were fed resmethrin in the basal diet at 0, 500, 800, or 1250 mg/kg. A decrease in pup weight and a slight increase in the number of pups cast dead were observed at the 500 mg/kg. Effects on the Environment In laboratory studies, resmethrin is highly toxic for fish with 96-h LC50 values of 0.3-5.5 ug/litre. Among the isomers, cismethrin is the most toxic for fish. However, under field conditions, it has been shown that the hazard is significantly reduced because of the rapid degradation and low water solubility of the compound. Resmethrin is less toxic for arthropods with 48-h LC50 values of 2-25 ug/litre. Both bioresmethrin and cismethrin are harmless for birds, (14-d LC50 and gt;5000). (Shortened)