NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 / ( 5 4 1 ) 3 4 4 - 5 0 4 4 JOURNAL OF PESTICIDE REFORM/ SUMMER 2003 • VOL. 23, NO. 2



## 10 ● INSECTICIDE FACTSHEET

Caroline Cox is NCAP’s staff scientist. 

### B Y



### C

AROLINE 

### C OX 

# S umithrin (see Figure 1) is an insecticide in the synthetic pyrethroidpesticide family. It is also called dphenothrin. Marketed as an insecticide since 1977, 1 

### it is sold by many pesticide companies using a variety of brand names, including Raid, Enforcer, Ortho, and Anvil. 2 

### There are about 250 sumithrin-containing pesticide products registered for sale in the U.S. 2 

### Pyrethroid insecticides are related chemically to the insecticidally active compounds called pyrethrins extractedfrom chrysanthemum flowers. Chemists have designed the structure of synthetic pyrethroids to make them both potent and stable in sunlight. 3

### Like most synthetic pyrethroid insecticides, sumithrin exists as a mixture of stereoisomers, 1 

### molecules that have the same atoms linked in the same order, but differ in their spatial arrangement. 4 

### Sumithrin is a mixtureof 2 stereoisomers which are both insecticidally active. 1 

### (See Figure 1.) Synthetic pyrethroid insecticides, 

# S UMITHRIN 

# ( D 

# -P HENOTHRIN 

# )

The synthetic pyrethroid insecticide sumithrin is commonly used to kill household insects and mosquitoes. The U.S. Environmental Protection Agency (EPA) estimates that about 100 million applications of sumithrin are made annually in U.S. homes, yards, and gardens.

Sumithrin is a neuropoison. Symptoms of exposure include dizziness, headache, fatigue and diarrhea.

In laboratory tests, sumithrin has damaged the liver and the kidneys. It has also caused anemia and increased the incidence of liver cancer.

In breast cancer cells, sumithrin increases the expression of a gene that is involved with proliferation of cells in the mammary gland. Sumithrin can also mimic certain activities of the sex hormone estrogen and keep another sex hormone from binding to its normal receptors.

Thousands of cat poisonings and some dog poisonings have been reported following the use of some sumithrincontaining flea control products.

Low concentrations of sumithrin (as low as one part per billion) kill fish and other aquatic animals. Sumithrin is also highly toxic to bees.



### Environmental Protection Agency (EPA) survey estimated in 1992 that almost 100 million applications of sumithrin were made annually in U.S. homes, yards, and gardens. About 2/3 of these applications occurred indoors. 6



### How Does Sumithrin Kill Insects? Sumithrin kills insects by disrupting the transmission of nerve impulses along axons, the elongated parts ofnerve cells. Synthetic pyrethroids allow excessive amounts of sodium atoms to enter nerve cells, stimulating the nerve cells and eventually causingparalysis. This mode of action is similar to that of the organochlorine insecticide DDT. 3 

### Pyrethroids’ effects on human nerves are similar to their effects on insect

nerves. 5 

### However, human nerves are generally less susceptible to pyrethroid poisoning. This is because human nerves are intrinsically less sensitive, pyrethroids are less potent at the higher body temperatures in humans, and human nerves recover more quickly from poisoning. 7



### Synergists About a dozen sumithrin products,including sumithrin, “are widely perceived as being safe” 5 

### according toone neurotoxicologist. However, sumithrin poses a variety of hazards for human and environmental health, and those are the focus of this article.

Use Sumithrin is primarily used to kill household insects, insects which pose public health problems (mosquitoes, for example), insects in stored grains, and lice. 1 

### The International Programme on Chemical Safety estimated in 1989 that worldwide use was about 70 to 80 tons per year; 1 

### more recent estimates are not publicly available. A U.S. Figure 1 Sumithrin

3-phenoxybenzyl (1R)- trans-chrysanthemate O

3-phenoxybenzyl (1R)- cis-chrysanthemate COO—CH 2

O COO—CH 2NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 / ( 5 4 1 ) 3 4 4 - 5 0 4 4 JOURNAL OF PESTICIDE REFORM/ SUMMER 2003 • VOL. 23, NO.2



## 11 including the Anvil products used tokill mosquitoes, contain piperonyl butoxide. 8 

### This chemical is used tosynergize (to make more toxic) sumithrin and other insecticides. Piperonyl butoxide is classified as a carcinogen by EPA, causes atrophied testes, and reduces the activity of importantimmune system components. For detailed information about the hazards of piperonyl butoxide see JPR 22(2):12- 20 or www.pesticide.org.
Inert IngredientsLike most pesticides, sumithrin insecticides contain ingredients in addition to sumithrin. Many of these ingredients, according to U.S. pesticide law, are called “inert.” 9 

### In general, they have not been publicly identified, and are not included in most of the testingrequired in order to register these pesticides. 10 

### “Inert Ingredients” (right) summarizes the hazards of some inert ingredients used in sumithrin products.
Symptoms of ExposureSumithrin and other synthetic pyrethroids are “neuropoisons” and symptoms of exposure are related to their effects on the nervous system. 11 

### According to Medical University of South Carolina physicians, acute (short-term) symptoms of exposure to sumithrinand other synthetic pyrethroids include “dizziness, salivation, headache, fatigue, diarrhea, and irritability to sound and touch.” 12



### Effects on the LiverAccording to a laboratory study submitted to EPA by a manufacturer as part of the registration process,sumithrin damages the liver. In a longterm (two-year) study in which ratswere fed sumithrin, the livers of exposed animals weighed more thanthose of unexposed animals. In addition, concentrations of enzymes that are indicators of liver damage increasedin exposed animals. These effects occurred at the middle and high dose levels tested in this experiment. 13 

### Similar increases in liver weight were found in studies of dogs fedsumithrin and rats breathing sumithrincontaminated air. Both studies were conducted as part of the registration
process. 14,15



### Effects on the Kidneys Two laboratory studies submitted aspart of the registration process suggest that male kidneys may be particularly susceptible to sumithrin. 16,17 

### (See Figure 2.) At all dose levels tested,



# “I NERT 

# ” I NGREDIENTS

Almost 100 sumithrin products contain petroleum distillates as inert ingredients. 1 

### One of these distillates is hydrotreated kerosene (Chemical Abstracts Services (CAS) number 64742-47-8). 2 

### According to the International Agency for Research on Cancer (IARC), exposure to hydrotreated kerosene caused skin tumors in a laboratory study. 3,4 

### Three other petroleum distillates (with CAS numbers 64742-55-8, 64742-56-9, and 64742-94- 5) are used in Anvil mosquito control products. 5,6 

### One of these petroleum distillates causes tremors and difficulty breathing, 7 

### the second caused skin tumors, according to IARC, 8,9 

### and the third contains two hazardous chemicals, naphthalene and trimethyl benzene. 10 

### Naphthalene exposure has caused lung tumors, cataracts, and anemia 11 

### while trimethyl benzene can depress the central nervous system and cause asthmatic bronchitis. 12 

### Many household sumithrin products are sold in aerosol spray cans, and these products often contain “inert” propellants that pose a variety of hazards. These propellants include propane and isobutane. 2 

### Both of these propellants can cause dizziness when inhaled and are “extremely flammable.” 13,14

1. Based on a survey of labels of sumithrin insecticide products conducted during May, 2003. Labels were retrieved from: U.S. EPA and Calif. Dept. of Pesticide Regulation. 2003. USEPA/ OPP chemical ingredients database. www.cdpr.ca.gov/docs/epa/epachem.htm. 2. U.S. EPA. 2002. Response to Freedom of Information Act request 01245-03. 3. National Institute for Occupational Safety and Health (NIOSH). 1997. Registry of Toxic Effects of Chemical Substances: Kerosene (petroleum), hydrotreated. ww.cdc.gov/niosh/rtecs/oa53fc00.html.4. International Agency for Research on Cancer (IARC). 1989. Occupational exposures in petroleum refining. IARC Monographs 45:39. www-cie.iarc.fr/htdocs/monographs/vol45/45-01.htm. 5. Clarke Mosquito Control Products, Inc. 1999. Material safety data sheet: Anvil 2+2 ULV. Rosedale, IL. 6. Clarke Mosquito Control Products, Inc. 1999. Material safety data sheet: Anvil 10+10 ULV. Rosedale, IL.7. NIOSH. 2000. Registry of Toxic Effects of Chemical Substances: Mineral oil, petroleum distillates, solvent - dewaxed light paraffinic (mild or no solvent - refining or hydrotreatment). ww.cdc.gov/niosh/rtecs/py7aa095.html.8. NIOSH. 2000. Registry of Toxic Effects of Chemical Substances: Mineral oil, petroleum distillates, hydrotreated (severe) light paraffinic. ww.cdc.gov/niosh/rtecs/py7aac4c.html.9. IARC. 1987. Mineral oils: Untreated and mildly-treated oils; Highly treated oils. IARC Monographs (Suppl. 7):252. www-cie.iarc.fr/htdocs/monographs/suppl7/mineraloils.html. 10. Shell Chemical Co. 2003. Material safety data sheet: Shellsol ® A150. ww.euapps.shell.com/ MSDS/GotoMsds. 11. IARC. 2002. Naphthalene. IARC Monographs 82:367. www-cie.iarc.fr/htdocs/monographs/vol82/82-06.html. 12. Hazardous Substance Data Bank (HSDB). 2002. 1,2,4-trimethylbenzene. http://toxnet.nlm.nih.gov. 13. HSDB. 2002. Propane. http://toxnet.nlm.nih.gov. 14. HSDB. 2002. Isobutane. http://toxnet.nlm.nih.gov. In male mice, sumithrin reduced kidney weight at all dose levels tested. Figure 2 Sumithrin Damages Kidneys

Source: U.S. EPA. Office of Pesticides and Toxic Substances. 1989. Memo from E.R. Budd, Health Effects Div. to J.M. Tavano, Registration Div. Washington, D.C., Mar. 16. See attached Data Evaluation Report for MRID No. 402764-02. Kidney weight (grams) 1.0

0.8

0.6

Sumithrin dose (100 mg per kg of body weight per day)

012 3 4 5NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 / ( 5 4 1 ) 3 4 4 - 5 0 4 4 JOURNAL OF PESTICIDE REFORM/ SUMMER 2003 • VOL. 23, NO. 2



## 12 on reproduction in laboratory studies. In the two-generation study of rats mentioned in the “Effects on Kidneys”section, the uterus was smaller in female rats exposed to the middle andhigh doses of sumithrin than in unexposed rats. 17

### In a second study of sumithrin’s effects on reproduction submitted during the registration process, pregnant rabbits exposed to sumithrin (at a dose of 500 mg/kg) had more miscarriages than unexposed rabbits. In addition,the sex ratio of the offspring of exposed mothers was different from that of unexposed mothers; more males were born to exposed animals. Also, a brain-related defect occurred in the offspring of rabbits exposed at the doselevel of 500 mg/kg. This defect, hydrocephaly, results in an abnormally large amount of fluid around the brain,leading to an enlarged skull and atrophy of the brain. 22



### Carcinogenicity (Ability to Cause Cancer) Sumithrin’s ability to cause cancer has not yet been evaluated by EPA (as of May 2002). 23 

### However, in two of the laboratory (45-450 milligrams per kilogram of body weight (mg/kg) per day), malemice exposed to sumithrin in a twoyear study developed smaller kidneys than unexposed males. 16 

### A study in which rats were fed sumithrin for two generations also found small kidneys in the first generation males. 17



### Effects on Blood In the study of dogs mentioned on p. 11, sumithrin exposure also caused anemia. In dogs fed sumithrin for one year, both the number of red blood cells and the amount of hemoglobin (the oxygen-carrying molecule in the blood 4 

### ) were decreased. 14 

### Anemia occurred at dose levels of 80 mg/kg per day. This was the highest dose tested in this study. 14



### Effects on HormonesThe impact of environmental contaminants on the functions of human and animal hormone systems has beena significant concern in the last decade. 18 

### Hormones are biologically active molecules that control all responses and functions of the body. Dramatic changes in the activity of cells in humans and other animals “are In laboratory tests, sumithrin disrupts the normal functioning of hormone systems. Figure 3 Sumithrin Mimics the Activity of a Sex Hormone

Source: Go, V. et al. 1999. Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environ. Health Persp. 107:173-177. Relative ability to express the pS2 gene 6

5

4

3

2

1

0

Unexposed Exposed to sumithrin (30 μ M) Figure 4 Sumithrin Displaces a Sex Hormone from its Receptors

Source: Eil, C. and B.C. Nisula. 1990. The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. J. Steroid Biochem. 35:409-414.



### caused by extremely small amounts” of hormones or other chemicals that disrupt this system. 19 

### Sumithrin has these kinds of effects on hormones. Researchers at the Mt. Sinai School of Medicine showed that sumithrin can mimic estrogens, sex hormones, in one of their biological activities. The researchers looked atthe activity of a gene called pS2 because the expression of pS2 is activated by estrogens. They found that in human cells sumithrin (as well asanother synthetic pyrethroid insecticide, fenvalerate) activates the expression in cells of pS2 like estrogens do. 20 

### (See Figure 3.) Sumithrin also keeps androgens, other sex hormones, from binding totheir normal receptors in human tissue. Scientists from Brown University and the National Institutes of Health showed that in genital skin cells sumithrin could displace an androgenfrom its normal receptors. When compared to other synthetic pyrethroids,sumithrin is intermediate in its displacement potency. 21 

### (See Figure 4.)
Effects on Reproduction Sumithrin has a variety of effects Exposed to an estrogen (10 nM) Note: Lines above bars are standard deviations

0 0.2 0.4 0.6 0.8 1.0 Bioallethrin

Fenvalerate

**Sumithrin**

Permethrin

Resmethrin

Relative ability to displace an androgen (Bioallethrin = 1)NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 / ( 5 4 1 ) 3 4 4 - 5 0 4 4 JOURNAL OF PESTICIDE REFORM/ SUMMER 2003 • VOL. 23, NO.2



## 13 carcinogenicity studies submitted in support of sumithrin’s registration, long-term (two-year) exposure to sumithrin increased the incidence of liver cancer. The studies include one done on mice and another done onrats. In the study with mice, liver cancer was relatively common (it occurredin 18 percent of the unexposed animals tested) and sumithrin exposure caused cancer incidence to increase to almost 25 percent. 16 

### In the study with rats, liver cancer was relatively rare (no liver cancer was found in unexposed animals) but increased to an incidence of almost 15 percent in exposed animals. 13 

### (See Figure 5.) In addition, a study from the Mt. Sinai School of Medicine links sumithrin with breast cancer. In this study, physicians used a culture of breast cancer cells. They looked at the expression of a gene that is involvedin the proliferation of mammary tissue, and therefore in the development of breast cancer. Exposure to sumithrin increased the expression of this gene. 24



### Synergy Enzymes called plasma esterases Programme on Chemical Safety,sumithrin is “very toxic to aquatic organisms.” 29 

### In tests submitted as part of sumithrin’s registration, the most sensitive fish species was the rainbow trout. The LC 50 

### (median lethal concentration; the dose that kills half of a test population) for rainbow trout was 1.4 parts per billion (ppb). All LC 50 

### s for fish were less than 100 ppb. 30

### The labels of about 80 sumithrincontaining insecticides contain warning statements about toxicity to fish. 8 

### Sumithrin also bioconcentrates infish. This means that the concentration of sumithrin in fish tissues is greater than the concentration in thewater in which the fish lives. According to a study conducted by Sumitomo Chemical Company, bioconcentration factors in carp range from 210 to 730. 31

### (The bioconcentration factor is the ratio between the concentration of achemical in fish tissues and the concentration in water. 32 

### ) When fish were simultaneously exposed to sumithrin and the synergist piperonyl butoxide (as in Anvil insecticide products), the bioconcentration factor of one form of sumithrin increased dramatically.Bioconcentration factors in this experiment varied from 2400 to 3800. 31



### Effects on Other Aquatic Animals Sumithrin is highly toxic to waterfleas, a species that is used in pesticide testing to represent aquatic animals. In a test submitted to EPA for sumithrin’s registration, concentrations of less than 1 ppb reduced successful egg hatch in water fleas. A slightly higher concentration (2 ppb) reduced the survival of larval water fleas. Sumithrin is even more toxic to shrimp; concentrations of 0.03 ppb killed mysid shrimp. 30



### Effects on Bees Since sumithrin is a broad spectruminsecticide, it is perhaps not surprising that tiny amounts of sumithrin kill bees. In a test submitted to EPA as part of sumithrin’s registration, 0.07 micrograms killed honey bees. 30 

### Thisputs sumithrin into EPA’s highest toxicity group for bee toxicity. This toxicity group includes any pesticides that detoxify pyrethroids in mammals. The activity of these enzymes is inhibited by a common family of insecticides, the organophosphates; this means that“simultaneous exposure to these insecticides will increase the toxicity of pyrethrins and pyrethroids.” 25



### Effects on PetsCats, especially young cats, are particularly susceptible to pyrethroid insecticides, possibly because cats’ livers are relatively slow in detoxifying pyrethroids. 26 

### Two sumithrin flea control products manufactured by Hartz Mountain Corporation have recentlycaused a large number of cat poisonings. EPA estimates that there were thousands of incidents, including somedeaths, between May 2000 and November 2002. At that time Hartz agreed to relabel the two products to reduce cat exposure. 27

### Seizures and death have also occurred after use of sumithrin on dogs, but not in as large numbers as the cat incidents. 28



### Effects on Fish According to the International

15

12

9

6

3

0 Figure 5 Ability of Sumithrin to Cause Cancer

Source: Calif. Environmental Protection Agency. Dept. of Pesticide Regulation. Medical Toxicology Branch. 1996. Summary of toxicology data: Phenothrin, June 20. www.cdpr.ca.gov/ docs/toxsums/toxsumlist.htm Percentage of animals with liver cancer

In a laboratory study of rats, sumithrin increased the incidence of liver cancer. 0 200 400 600 800 1000

Dose of sumithrin (milligrams per kilogram of body weight per day)NORTHWEST COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 / ( 5 4 1 ) 3 4 4 - 5 0 4 4 JOURNAL OF PESTICIDE REFORM/ SUMMER 2003 • VOL. 23, NO. 2



## 14 kill bees in amounts of 2 micrograms per bee or less. 33



### Resistance

Insecticide resistance occurs when repeated exposure over generations kills the most susceptible individuals in an insect population. The survivorshave genetically determined characteristics that allow them to survive exposures to the insecticide that would usually be lethal. 34

### Sumithrin resistance has been reported in cockroaches, aphids, mosquitoes and lice. 35-38 

### The resistance ratio, the ratio between the amount ofsumithrin needed to kill a resistant insect and the amount needed to kill a susceptible one, can be over 50 in both cockroaches and lice. 36,39,40 

### The synergist piperonyl butoxide is sometimes used to “negate” resistance, to kill resistant individuals, but is not always successful. 34 

### Sumithrin resistance can be quite common. French physicians found that 60 percent of the lice populations in the Paris elementary school studentsthey studied were resistant to sumithrin. 38 

### Widespread resistance has also been found in lice in the United Kingdom. 41 

### Insects resistant to one pyrethroid insecticide are often resistant to many pyrethroids. This means that insects can develop resistance to sumithrin without actually having been exposed to the insecticide. 42



### References

1. United Nations Environment Programme, International Labour Organization, and World Health Organization. 1989. d-Phenothrin health and safety guide. IPCS International Programme on Chemical Safety. Health and Safety Guide No. 32. www.inchem.org.2. U.S. EPA and Calif. Dept. of Pesticide Regulation. 2003. USEPA/OPP chemical ingredients database. www.cdpr.ca.gov/docs/epa/ epachem.htm. 3. Ware, G.W. 2000. The pesticide book. 5th edition. Fresno CA: Thomson Publications. Pp. 65- 67,177-178. 4. National Library of Medicine. Undated. Medline Plus health information; Medical dictionary. www.nlm.nih.gov/medlineplus/mplusdictionary.html. 5. Soderlund, D.M. 2002. Agents affecting sodium channels. In Handbook of neurotoxicology, vol. 1 , ed. E.J. Massaro. Totowa NJ: Humana Press Inc. Pp. 47-68. 6. Whitmore, R.W., J.E. Kelly, and P.L. Reading. 1992. National home and garden pesticide use survey. Final report, vol. 1: Executive summary,results, and recommendations. Table G.1. Research Triangle Park NC: Research Triangle Institute.7. Narahashi, T. et al. 1998. ion channels as targets for insecticides. NeuroToxicology 19:581- 590.8. Based on a survey of labels of sumithrin insecticide products conducted during May, 2003. Labels were retrieved from: U.S. EPA and Calif. Dept. of Pesticide Regulation. 2003. USEPA/ OPP chemical ingredients database. www.cdpr.ca.gov/docs/epa/epachem.htm. 9. Federal Insecticide, Fungicide and Rodenticide Act § 2(a) and 2(m). 10. 40 Code of Federal Regulations § 158.340.11. United Nations Environment Programme, International Labour Organization, and World Health Organization (WHO). 1990. d-Phenothrin . Environmental Health Criteria 96. Geneva, Switzerland: WHO. Pp. 9-10. 12. Reigart, J.R. and J.R. Roberts. 1999. Recognition and management of pesticide poisonings. Fifth edition. Washington, D.C.: U.S. EPA. Pp. 87-88. www.epa.gov/pesticides/safety/ healthcare. 13. Calif. Environmental Protection Agency. Dept. of Pesticide Regulation. Medical Toxicology Branch. 1996. Summary of toxicology data: Phenothrin, June 20. www.cdpr.ca.gov/docs/ toxsums/toxsumlist.htm14. U.S. EPA. Office of Pesticides and Toxic Substances. 1989. Sumithrin (d-phenothrin) - reviewof toxicity studies submitted by Sumitomo Chemical Company in support of EAP#1H45283 and EPA Registration No. 10308-6. Memo from E.R.Budd, Health Effects Div. to J.M. Tavano, Registration Div. Washington, D.C., Mar. 16. See attached Data Evaluation Report for MRID No. 402764-01. 15. U.S. EPA. Office of Prevention, Pesticides, and Toxic Substances. 1995. D-phenothirin (sumithrin) -submission of a 90-day inhalationtoxicity study in rats. (EPA ID 06905). Washington, DC, June 13.16. U.S. EPA. Office of Pesticides and Toxic Substances. 1989. Sumithrin (d-phenothrin) - reviewof toxicity studies submitted by Sumitomo Chemical Company in support of EAP#1H45283 and EPA Registration No. 10308-6. Memo from E.R.Budd, Health Effects Div. to J.M. Tavano, Registration Div. Washington, D.C., Mar. 16. See attached Data Evaluation Report for MRID No. 402764-02.17. U.S. EPA. Office of Pesticides and Toxic Substances. 1989. Sumithirin (d-phenothrin - review of rat reproduction study. Memo from W. Dykstra, Health Effects Div. to J. Tavano, Registration Div. Washington, D.C., Jul. 27. 18. National Research Council. Commission on the Life Sciences. Board on Environmental Studiesand Toxicology. Committee on Hormonally Active Agents in the Environment. 1999. Hormonally active agents in the environment. Washington, D.C.: National Academy Press, p. 10. 19. Eubanks, M.W. 1997. Hormones and health. Environ. Health. Persp. 105:482-487.20. Go, V. et al. 1999. Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environ. Health Persp. 107:173-177.21. Eil, C. and B.C. Nisula. 1990. The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. J. Steroid Biochem . 35:409-414.22. U.S. EPA. Office of Pesticides and Toxic Substances. 1991. Sumithrin. Review of developmental toxicity in rabbits. Memo from P.M. Hurley, Health Effects Div., to R. King, Reregistration Div. Washington, D.C., Nov. 7.23. U.S. EPA. Office of Pesticide Programs. Science Information Management Branch. HealthEffects Division. 2002. List of chemicals evaluated for carcinogenic potential. Unpublished document dated May 22.24. Kasat, K., V. Go, V., and B.G. Pogo. 2002. Effects of pyrethroid insecticides and estrogen on WNT10B proto-oncogene expression. Environ. Int. 28:429-432. 25. Campbell, A. and M. Chapman. 2000. Handbook of poisoning in dogs and cats. Malden MA: Blackwell Science. Pp. 44. 26. Ref. # 25, pp. 42-45. 27. U.S. EPA. Undated. Questions and answers:Label instructions tightened on flea & tick control products for pets. www.epa.gov/pesticides/ factsheets/hartzq_a.htm. 28. U.S. EPA. Office of Prevention, Pesticides and Toxic Substances. Undated. Review of incidentdata for four Hartz Mountain flea and tick control products (2596-146, -147, -148, -150). Memo from V.A. Dobozy, Health Effects Div. to A. Layne, Registration Div. and others. 29. International Programme on Chemical Safety and the Commission of European Communities. 2001. d-Phenothrin. ICSC:0313. www.inchem.org/documents/icsc/icsc/ eics0313.htm. 30. U.S. EPA. Office of Pesticide Programs. 2003. Pesticide ecotoxicity database. Unpublished. Received from EPA on May 13. 31. Miyamoto, M. et al. 1992. Effect of metabolismon bioconcentration of geometric isomers of dphenothrin in fish. Chemosphere 24:2001-2007. 32. BioTech Resources and Indiana Univ. 1995-98. BioTech life science dictionary. http:// biotech.icmb.utexas.edu/search/dict-search.html.33. U.S. EPA. Office of Pesticide Programs. Undated. Label review manual. Chap. 9. Environmental hazards. www.epa.gov/oppfead1/labeling/ lrm/chap-09.htm.34. Cochran, D.G. 1995. Insect resistance to pyrethrins and pyrethroids. In J.E. Casida and G.B. Quistad, eds. Pyrethrum flowers: Production, chemistry, toxicology, and uses. New York NY: Oxford Univ. Press. p. 234-248. 35. Michigan State Univ. Center for Integrated Plant Systems. Undated. The database of arthropodsresistant to pesticides. www.cips.msu.edu/resistance. (See entries for both sumithrin and phenothrin.) 36. Picollo, M.I. et al. 1998. Laboratory studies of susceptibility and resistance to insecticides in Pediculus capitis (Anoplura; Pediculidae). J. Med. Entomol. 35:814-817.37. Picollo, M.I. et al. 2000. Resistance to insecticides and effect of synergists on permethrin toxicity in Pediculus capitis (Anoplura: Pediculidae) from Buenos Aires. J. Med. Entomol. 37:721- 725. 38. Chosidow, O. et al. 1994. Controlled study of malathion and d-phenothrin lotions for Pediculus humanus var capitis -infested schoolchildren. The Lancet 344:1724-1727. 39. Cochran, D.G. 1989. Monitoring for insecticideresistance in field-collected strains of the German cockroach (Dictyoptera:Blatellidae). J. Econ. Entomol. 82:336-341. 40. Lee, C.Y. et al. 1996. Insecticide resistance and synergism in field collected German cockroaches (Dictyoptera:Blatellidae) in peninsular Malaysia. Bull. Entomol. Res. 86:675-682.41. Downs, A.M.R. et al. 2002. Widespread insecticide resistance in head lice to the over-thecounter pediculocides in England, and the emergence of carbaryl resistance. Br. J. Dermatol. 146:88-93.42. Cochran, D.G. 1987. Selection for pyrethroid resistance in the German cockroach (Dictyoptera:Blattellidae). J. Econ. Entomol. 80:1117-1121.