Toxicologic Information About Insecticides
Used for Eradicating Mosquitoes
(West Nile Virus Control)
April 2005
Phenothrin, also known as sumithrin, is a synthetic pyrethroid. It is an insecticide registered for use against mosquitoes in swamps, and recreational areas. Phenothrin can be used to kill pests in aircrafts, ships, railroad cars and truck trailers, and for institutional non-food use. It can be used in homes, gardens, greenhouses and on pets (EPA 2005). Phenothrin is also formulated in powders, shampoos, and lotions to control human lice. In addition, it is used to protect stored grains. Racemic phenothrin was first synthesized in 1969 and is a mixture of four stereoisomers. d-Phenothrin is the 1:4 mixture of the [1R, cis] and [1R, trans] isomers and has been in use since 1977. d-Phenothrin is currently the only technical product commercially available (WHO 1990). Phenothrin breaks down rapidly in the environment and is expected to pose little risk to humans when used at low concentrations for mosquito control (EPA 2005).
Section 1. Environmental Factors
Phenothrin undergoes rapid photodegradation under outdoor conditions, with a half-life of less than 1 day on plants and other surfaces. It is transported to a very minor extent from the site of application on plants and in soils. Limited uptake of radiolabelled products into bean plants took place from soils treated with 14C-phenothrin. When soils were treated with phenothrin, it decomposed rapidly with initial half-lives of 1-2 days, but under flooded conditions the degradation was much slower from 2 weeks to 2 months. Very little movement was observed through soil columns when leaching was started immediately or 14 days after treatment with phenothrin (WHO 1990). If released into water, phenothrin is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Estimated volatilization half-lives for a model river and model lake are 7 and 81 days, respectively. However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column (HSDB 2005). The degradative processes that occur in the environment generally lead to less toxic products (WHO 1990).
When phenothrin was applied to ponds at the rates of 28 or 56 g/ha to control mosquito larvae, mayfly naiads were most affected but no other arthropods were seriously affected. In fish, phenothrin has 96-hour LC50 values of 17-200 µg/liter (WHO 1990).
Section 2. Potential for Exposure
Occupational exposure to phenothrin may occur through inhalation and dermal contact with this compound at workplaces where phenothrin is produced or used. The general population may be exposed to phenothrin via contact with insecticides containing phenothrin (HSDB 2005). Thus, the general population is exposed to phenothrin from conventional household aerosol spraying; when used to control lice; and from residues on stored wheat. Conventional household aerosol spraying is not expected to lead to aerial levels of phenothrin greater than 0.5 mg/m3. Residues of up to 4 mg/kg may be present in stored wheat, but this decreases after milling to 0.8 mg/kg in flour and to 0.6 mg/kg after baking (WHO 1990).
Section 3. Health Effects/Toxicity
Almost all systemic effects resulting from exposures to pyrethroids are related to their action on the nervous system. Pyrethroids exert their profound effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. In rodents, effects such as tremors are induced if the open state is prolonged for brief periods; effects such as sinuous writhing (choreoathetosis) and salivation occur if the open state is prolonged for longer periods. Neurologic signs typically result from acute toxicity. Low-level chronic exposures to pyrethroids usually do not cause neurologic signs in mammals, largely because of rapid metabolism and elimination. Data from animal studies do not indicate that pyrethroids significantly affect end points other than the nervous system, although changes in liver weight and metabolism of chemicals sometimes have been used as an index of adverse effect levels for pyrethroids. A few recent animal studies indicate the potential for adverse neurodevelopmental, reproductive, and immunologic effects at exposure levels below those expected to result in overt signs of neurotoxicity. Data do not indicate that pyrethroids should be considered a carcinogenic concern to humans. No data in humans are available regarding the potential for pyrethroids to cross the placental barrier and enter a developing fetus. Limited data from animals indicate that transfer of pyrethroids across the placenta to the fetus may result in persistent effects on neurotransmitters later in life. Although pyrethroids have not been identified in human breast milk, very low levels of pyrethroids (<1% of an orally administered dose) are excreted into milk of lactating animals (ATSDR 2001).
Phenothrin has been used for many years and no toxic effects or cases of poisoning have been reported. In one human study by Hashimoto et al. (1980), phenothrin in a talc powder formulation was applied to the head hair and pudenda hair of 8 male human volunteers 3 times at intervals of 3 days at a dose of 32 mg/person per administration (0.44 to 0.67 mg/kg/day). Phenothrin powder was washed off 1 hour after application. There were no significant abnormalities observed in terms of dermal irritation, clinical signs, or blood biochemical and hematological parameters. The blood levels of phenothrin were below the detection limit of 0.006 mg/kg (WHO 1990).
Studies in laboratory animals exposed to phenothrin dermally, orally, or by inhalation are summarized in Table 1, with no-observed-adverse-effect levels (NOAELs) and lowest-observedadverse- effect levels (LOAELs) indicated.
The acute toxicity of phenothrin is extremely low. The dermal LD50 for phenothrin is >5,000 mg/kg in the rat and mouse. Oral LD50 values for phenothrin in rats range from >500 to >10,000 mg/kg. The oral LD50 for mice also range from >500 to >10,000 mg/kg. When phenothrin was given to Sprague Dawley rats orally for 5 consecutive days at 5,000 mg/kg/day, the authors concluded that phenothrin does not lead to the neurotoxic effects observed with several other pyrethroids (Okuno et al., 1978 in WHO 1990). The 4-hour inhalation LC50 for phenothrin in rats ranged from >1,210 to 3,760 mg/m3 and from >1,210 to >1,180 mg/m3 in mice (WHO 1990). No adverse toxicological effects were observed when rats were exposed by inhalation to phenothrin at concentrations up to 210 mg/m3 (Kohda et al. 1979).
Several longer term studies of phenothrin have been conducted in rats and mice with exposure periods of 6 months (Murakami et al. 1981) to 2 years (Amyes et al. 1987; Hiromori et al. 19; Martin et al. 1987; Murakami et al. 1980,1981). The no-observed-effect levels from these studies were 300- 1,000 mg/kg diet (approximately 40-160 mg/kg/day). A slight increase in liver weight and a significant difference in some clinical chemistry parameters from those of controls were observed at high doses in these studies. In the 2-year studies, phenothrin was not oncogenic to rats or mice at dietary levels of up to 3,000 mg/kg. Similar results were seen in two dog feeding studies with exposure periods of 26-52 weeks at doses of 100-3,000 mg/kg diet with a no-observed-effect level of 300 mg/kg diet (7-8 mg/kg/day) (Cox et al. 1987; Pence et al. 1981). Again, no tumorigenicity related to phenothrin was detected in these dog studies.
Table 1. Health Effect Levels of Phenothrin in Laboratory Animals
(PDF Version 67k)
Neither teratogenicity nor embryotoxicity was observed in fetuses of rabbits and mice orally administered phenothrin at up to 1,000 and 3,000 mg/kg, respectively (Ladd et al. 1976; Rutter 1974; Nakamoto et al. 1973). In a 3-generation rat reproduction study, no reproductive effects were seen at 2,000 mg/kg (Takasuka et al. 1980). In a 2-generation rat reproduction study, the no-observed-effect level was 1,000 mg/kg diet, with a slight increase in relative liver weights observed at 3,000 mg/kg (Tesh et al. 1978)..
Phenothrin did not exhibit any mutagenic properties or cause chromosomal or DNA damage in a variety of in vivo and in vitro test systems (WHO 1990).
There have been a number of studies showing that after rats were given single or repeated oral exposure or dermal treatment with radiolabelled phenothrin, the radiolabel was rapidly and almost completely excreted in urine and feces within 3-7 days. The major metabolic pathways of phenothrin in rats were ester cleavage and oxidation at the 4’-position of the alcohol moiety or the isobutenyl group of the acid moiety (WHO 1990).
Section 5. Standards and Guidelines for Protecting Human Health
Regulatory standards and guidance values are summarized in Table 2.
An acceptable daily intake (ADI) of 0-0.07 mg/kg body weight has been established by WHO (1990).
| Table 2. Regulatory Standards and Guidance Values for Phenothrin | ||
| Standard/Guidance | Value | Reference |
| World Health Organization acceptable daily intake (ADI) | 0-0.07 mg/kg | WHO 1990 |
Amyes SJ, Martin PA, Ashby R, et al. 1987. Sumithrin: Oncogenicity and toxicity study in mice. Suffolk, United Kingdom, Life Science Research. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Cox RH, Sutherland JD, Boelker RW, et al. 1987. Chronic toxicity study in dogs with Sumithrin technical grade. Vienna, Virginia, Hazleton Laboratories Inc. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
EPA. 2005. Pesticides: Topical and Chemical Fact Sheets. Pesticides and Mosquito Control. US Environmental Protection Agency. Available at http://www.epa.gov/pesticides/factsheets/mosquitocontrol.htm.
Hashimoto T, Koyama Y, Okuno Y, et al. 1980. Human volunteer study with phenothrin and d-phenothrin powder. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Hiromori T, Koyama Y, Okun Y, et al. 1980. Two year chronic toxicity study of S-2539 in rats. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
HSDB. 2005. Hazardous Substances Data Bank, National Library of Medicine. National Toxicology Program. Accessed March 15, 2005.
Kohda H, Nishimoto K, Kodota K, Miyamoto J. 1979. Acute and subacute inhalation toxicity studies of S-2539 Forte in rats and mice. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Ladd R, Smith PS, Jenkins DH, et al. 1976. Teratogenic study with S-2539 in albino rabbits. Northbrook, Illinois, Industrial Bio-test Laboratories. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Martin PA, Amyes SJ, Ashby R, et al. 1987. Sumithrin: Combined toxicity and oncogenicity study in rats. Suffolk, United Kingdom, Life Science Research. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Murakami M, Hiromori T, Ito S, Hosokawa S. 1981. Six month oral toxicity study of S2539 Forte (Sumithrin (R)) in rats. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Murakami J, Ito S, Okuno Y, et al. 1980. Eighteen month chronic oral toxicity and tumorigenicity study of S-2539 in mice. Northbrook, Illinois, Industrial Bio-test Laboratories. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Nakamoto N, Kato T, Miyamoto J. 1973. Teratogenicity study of S-2539 Forte in mice. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Okuno Y, Kadota T, Miyamoto J. 1978. Neurotoxicity study of d-phenothrin in rats by repeated oral administration. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Pence DH, Hagen WH, Wilsaker RD, et al. 1981. Subchronic toxicity study of S2539-F in dogs. Vienna, Virginia, Hazleton Laboratories Inc. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Rutter HA. 1974. Teratogenicity study in rabbits: S-2539 Forte. Vienna, Virginia, Hazleton Laboratories Inc. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Takatsuka M, Okuno Y, Suzuki T, et al. 1980. Three-generation reproduction study of S-2539 in rats. Northbrook, , Illinois, Industrial Bio-test Laboratories. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
Tesh JM, Willoughby CR, Fowler JSL. 1987. Sumithrin: Effects upon reproductive performance of rats treated continuously throughout two successive generations. Suffolk, United Kingdom, Life Science Research. Unpublished report submitted to WHO by Sumitomo Chemical Co. (Cited in WHO 1990)
WHO. 1990. Environmental Health Criteria 96: d-Phenothrin. International Programme on Chemical Safety. Genevia: World Health Organization.
« Naled |
Permethrin »
Table of Contents
