Safety of pesticides used to control adult mosquitoes

SAFETY OF PESTICIDES USED TO CONTROL ADULT MOSQUITOES
(Pyrethrins, Pyrethroids, and Piperonyl Butoxide)
Questions and Answers for Public Health Professionals
Division of Environmental and Occupational Disease Control
Division of Communicable Disease Control
California Department of Health Services

1. What is the primary method used to control West Nile virus?

Mosquito control is the most effective means of reducing the risk of people becoming
infected with West Nile virus (WNV). Mosquito control targets both the aquatic,
immature stages of the mosquito and the adult stage (CDHS, 2005a).

Larval control
Control of larval mosquitoes is the backbone of most mosquito control programs in
California. Pesticides added to the water to kill mosquito larvae are called larvicides.
These products may be applied by hand, with a power backpack, from all terrain
vehicles (ATV’s) or trucks, and in very large or inaccessible areas with helicopters and
airplanes. Pesticides used for larviciding include, bacterial products (Bacillus
thuringiensis var. israelensis (Bti) and B. sphaericus (Bs)); surface agents (highly
refined mineral oils or monomolecular films that spread across the surface of the water);
and insect growth regulators methoprene and dimilin (chemicals that are added to the
water to disrupt the normal maturation process of mosquito larvae). For more
information on larvicidal agents, please refer to the fact sheet titled “Pesticides and
Mosquito Control” (US EPA, 2002).
Adult mosquito control
Adult mosquito control is a means to rapidly knockdown biting adult mosquitoes. This
can become necessary when larval control measures are insufficient or not feasible.
Adulticiding may be initiated when there is evidence of significant WNV transmission in
a region. The most common method of adult mosquito control (adulticiding) is ultra-low
volume (ULV) spraying. ULV spraying (also occasionally called cold fogging) is the
process of putting very small amounts of liquid (typically 4 ounces per acre or less) into
the air as a fine mist of droplets. These droplets float on the air currents and quickly kill
mosquitoes that come into contact with them. ULV adulticides are applied when
mosquitoes are most active – typically early evening or pre-dawn.
ULV spraying is usually done over geographic areas consisting of several acres to
many square miles. Unlike agricultural or structural pesticide applications where the
chemical is applied directly to a crop or structure, a ULV formulation is sprayed into the
air column where it can contact and kill active mosquitoes. Aerial movement of the ULV
product is an essential part of the application. ULV applications are only done during
environmental conditions that ensure desirable product movement.
2. What pesticides are used to control mosquitoes that carry West Nile virus?
In California, two classes of pesticides, each combined with a synergist chemical, are
commonly used for adult mosquito control.
Pyrethrins are the active ingredients in pyrethrum, an extract of the African flower
Chrysanthemum cineriaefolium. Pyrethrins are natural insecticides that act by blocking
chemical signals at nerve junctions.

Pyrethroids are synthetic pesticides that are very similar to pyrethrins in their chemical
structure and mode of action. Permethrin, resmethrin, sumithrin, and deltamethrin are
pyrethroid insecticides that may be used for adulticiding. D-phenothrin is another
pyrethroid pesticide that has been used for ULV spraying, but not in California.
Pyrethroids are more light-stable and have a longer duration of activity against insects
than pyrethrins.
Piperonyl butoxide (PBO) is a synergist that is usually incorporated with pyrethrins and
pyrethroids. PBO enhances the effect of these insecticides by inhibiting cytochrome
P450, a class of enzymes that break the down the pesticides. This allows the
insecticides to be effective with less active ingredient than would otherwise be required.
In addition, as with all pesticide formulations, the pesticides used for adulticiding contain
inactive ingredients, typically petroleum distillates.
Pyrethrins, pyrethroids, and PBO are widely used for home, garden, agricultural and
structural (building) pesticide applications. They are also found in products to control
head lice or the fleas on pet animals.
3. How do these pesticides work?

Both pyrethrins and pyrethroids act on the nervous system of insects by inactivating
sodium channels in the insect nervous system. Because mammals rapidly detoxify
these compounds, humans are less susceptible to systemic effects by this mode of
action.
4. Who approves the use of these pesticides?

US EPA approves the use of pesticides nationally and the California Department of
Pesticide Regulation (CDPR) approves their use in California. Before pesticides are
registered by US EPA or CDPR, they must undergo laboratory testing for acute and
chronic health effects. In these tests, laboratory animals are purposely fed a pesticide
at high doses (usually the pure or technical material) for an extended period of time
specifically to see if toxic effects occur. These tests help scientists judge how these
chemicals might affect humans, domestic animals, and wildlife in the case of exposure.
The US EPA has guidelines that require testing of pesticides for their potential to cause
cancer. These studies involve feeding laboratory animals large daily doses of the
pesticide over most of the lifetime of the animals. Based on these tests, as well as any
other available information, EPA gives the pesticide a rating for its potential to cause
cancer in humans.
5. What are the potential health effects of pyrethrins and pyrethroids?

Acute

Pyrethrins
In acute oral dosing studies with pyrethrins, rats exhibited difficulty breathing, lack of
coordination, sprawling of limbs, tremors, aggression, sensitivity to external stimuli,
twitching and exhaustion (Litchfield, 1985).
In humans, dermatitis is the most common health effect reported following direct contact
with pyrethrins. Descriptions range from local erythema to vesicular eruptions
(Ecobichon, 1990). These dermal effects may be due to allergenic or irritant effects of
pyrethrins, or to irritation caused by PBO or by petroleum distillates used in the
formulation process (O’Malley, 2001).
Allergic rhinitis, conjunctivitis, and asthma have been reported following human
exposure to pyrethrins. Rare but potentially severe reactions following direct dermal or
respiratory exposure to pyrethrins include hypersensitivity pneumonitis, nonfatal and
fatal anaphylactic reactions (Carlson, 1977; CDC, 2000; Wagner, 1994; Wagner, 2000;
Wax, 1994).
The chief allergen in unpurified pyrethrins is a lactone compound, pyrethrosin (Penagos
et al., 2001). Current pyrethrin formulations are purified and theoretically do not contain
the lactone sensitizer. Sensitization reactions to purified pyrethrin products have not
been well documented in the recent literature (Penagos et al., 2001).
Pyrethroids
Although allergic contact dermatitis and asthma due to pyrethroids have been alleged,
they have not been well documented (Kolmodin-Hedman, 1982; Wagner, 1994;
Penagos et al., 2001). Unique skin paresthesias, manifested by numbness, itching,
burning, tingling, and warmth, and often described as a sensation of insects crawling on
the skin, have been described following exposure to certain pyrethroids. The
paresthesias are due to the effects on sodium channels of the nerve terminals in skin
(Penagos et al., 2001).
Based on occupational studies, mild acute exposure may result in dizziness, headache,
nausea, anorexia and fatigue. At high doses, such as when workers have been soaked
with concentrated pyrethroids, or after intentional ingestion, the following symptoms
have been reported: muscular fasciculations, convulsions, pulmonary edema, and coma
(He et al., 1989)
Piperonyl Butoxide
PBO causes skin irritation in laboratory animals, but no skin irritation was observed in
human studies (NPTN, 2000; Penagos et al., 2001). No other acute health effects due
to PBO alone have been reported. This may be partly due to the fact that it is not used
alone but in conjunction with other pesticides.
Petroleum Distillates
The term “petroleum distillate” encompasses a wide variety of petroleum-based
compounds. In general, this class of compounds may produce eye, skin, and respiratory
irritation, and symptoms of CNS depression, such as headache, dizziness, nausea, and
vomiting. Since the components of petroleum compounds are “volatile”, they will
“evaporate” from any solid surface within hours.
Chronic

Pyrethrins
The data on reproductive toxicity of pyrethrins in animals varies by species. Rabbits fed
moderate doses (up to 90 mg/kg) of pyrethrins during a sensitive period of pregnancy had
normal litters. There were no birth defects in rabbit litters exposed to pyrethrins. Rats fed
very high doses (5,000 mg/kg) of pyrethrins for three weeks before their first mating
produced a low birth weight litter (CDPR, 2005). As is typical for many chemicals, human
data on reproductive toxicity on pyrethrins are lacking.
US EPA classified pyrethins as “likely to be carcinogenic to humans by the oral route” in
1999 (US EPA, 1999). This evaluation was based on results from standard two-year
carcinogenicity studies where rats and mice were exposed to high-dose pyrethrins in
their diet. In those studies, the incidence of thyroid tumors was greater in male and
female rats exposed to pyrethrins than in untreated control rats. In addition, pyrethrin-
treated female rats developed benign liver tumors. US EPA re-evaluated pyrethrins in
2004 and classified pyrethrins in the group: “Suggestive evidence of carcinogenicity but
not sufficient to assess human carcinogenic potential” (US EPA, 2004). This category
is described as one “which raises a concern for carcinogenic effects but is judged not
sufficient for a conclusion as to human carcinogenic potential.” Researchers found that
farmers exposed to pyrethrins used for pest control on livestock had an increased risk of
developing leukemia (Brown et al., 1990). Because farmers are exposed to multiple
chemicals, these results require further study to evaluate the specific effects of
pyrethrins.
Pyrethroids
Rats fed high doses of resmethrin had litters with decreased viability and body weight
gain at the high dose in rats; rabbits fed high doses of resmethrin showed an increase in
abortions and fetal resorptions (CDPR, 2005). In one animal study, permethrin impeded
fertility but was not teratogenic. Permethrin and resmethrin are not mutagenic.
Specific pyrethroids have been evaluated for their potential to cause cancer.
Permethrin has been classified by US EPA in the category “Suggestive evidence of
carcinogenicity, but not sufficient to assess human carcinogenic potential.” Other
pyrethroids are classified as possible human carcinogens (Group C) where US EPA
concluded that there was limited evidence of carcinogenicity in animals. This category
is similar to the “suggestive evidence of carcinogenicity” category. Pyrethroids
classified as Group C include bifenthrin, tetramethrin and cypermethrin. These
pyrethroids, which are not commonly used for WNV mosquito control, increased
incidences of urinary bladder and liver tumors in mice (bifenthrin), testicular interstitial
cell tumors in male rats (tetramethrin), and lung tumors in female mice (cypermethrin).
Not all pyrethroid insecticides have been evaluated for cancer risk. For two pyrethroids
commonly used for WNV adulticiding (sumithrin and resmethrin), no US EPA evaluation
is available.
Some pyrethroids have tested positive in cytogenetic studies. For example, some
pyrethroids (permethrin, cypermethrin, deltamethrin, and fenvalerate) increased
chromosome damage (chromosomal aberrations) in bone marrow cells of mice after
treatment with the insecticide (ATSDR, 2003). There is some evidence that
chromosomal aberrations may predict cancer risk.
Pyrethroids may affect endocrine hormone function at high doses. Permethrin was
associated with gynecomastia (excessive development of the male mammary glands) in
male Haitian refugees treated with the insecticide in the early 1980’s (Brody, 2003).
Since then, high dose in vitro studies have shown the anti-androgenic activity of several
pyrethroids (Eil, 1990). Some pyrethroids have been found to be estrogenic in in vitro
studies (Kim et al., 2004; Go et al., 1999; Garey, 1998). However, adverse endocrine
disruption effects (anti-androgenic or estrogenic effects) were not observed when
esfenvalerate, fenvalerate, or permethrin were administered at lower doses to rats
(Kunimatsu et al., 2002). The clinical implications of these findings are unclear and they
need to be further investigated in terms of potential effects of pyrethroids on the
development of both cancer and reproductive toxicity in humans.
Piperonyl Butoxide
PBO is not a developmental or reproductive toxicant in animals.
Two published studies have shown that PBO administered long-term in the diet to male
female rats and mice produced treatment related increases in liver cancer (Takahashi et
al., 1994; Takahashi et al., 1997). However, several other studies in rats did not find
evidence of carcinogenic potential (NTP, 1979; Maekawa et al., 1985; Butler et al.,
1998). A more recent EPA (1995) review rates PBO as a “Group C (Possible Human
Carcinogen”), although this classification pre-dates several of the available studies. As
stated above, EPA defines Group C such chemicals as agents with limited evidence of
carcinogenicity in animals in the absence of human data.
6. How safe are these pesticides?

No pesticide is completely safe. All individuals should take steps to minimize exposure
to any pesticide.
While the pesticides used for mosquito control can cause adverse health effects under certain circumstances, described above, the available data suggest that they are relatively safe when applied by ULV spraying according to label instructions for the following reasons. Pesticides are unstable Pyrethrins are extremely photosensitive and break down within hours in the presence of sunlight and air. Evening applications are likely to degrade by the morning, and much of the product does not reach the ground (Moore, 1993; Knepper, 1996). While pyrethroids are more stable, this varies with the compound. Permethrin has a half-life of about five days in sunlight and resmethrin is more stable, with a half life of about 30 days (Beasley, 2000). The half-life of PBO is about four days in soil and up to two days in water (NPTN, 2000). Very low dosage rates of pesticides are used Typically less than one ounce per acre is applied either the ground or air. An application rate of 0.66 ounces of product per acre (0.0025 pounds per acre), which is typical for pyrethrin products, equate to 0.000015 ounce per square foot, assuming that all of the pesticide reaches the ground. Pesticides are poorly absorbed through the skin Pyrethrins, pyrethroids, and piperonyl butoxide are all poorly absorbed through the skin (Franz, 1996; Wester et al., 1994). When applied directly to the scalp of human volunteers, as in shampoo applications, absorption is greater (approximately 8%) than when applied to the forearm (approximately 2%), (Wester et al., 1994). No evidence of exposure following ULV spraying The only study to quantitate human exposure to pesticides following spraying for WNV found that there was no increase in urine metabolite concentrations of the metabolites of naled (an organophosphate), permethrin, or d-phenothrin after ULV spraying compared with baseline (CDC, 2005). Use of sensitive analytic methods in these studies indicated that the urine pesticide metabolite concentrations measured were low (parts per billion). The concentration of urine metabolites were comparable with those measured in the general population (CDC, 2003b; Heudorf, 2001). In certain participants, investigators found an association between home and/or work application of pesticides and pesticide metabolite concentrations. The Centers for Disease Control and Prevention (CDC) has detected several permethrin metabolites in urine samples across a broad spectrum of the US population, suggesting that in spite of relatively low environmental stability and poor skin absorption, human exposures occur commonly (CDC, 2005). CDC did not evaluate the reason for permethrin applications or whether applications and exposures occurred indoors or outdoors. Indoor pyrethrin and pyrethroid applications are more persistent, and therefore indoor exposure levels may be higher than those that occur outdoors. Population health effects following spraying From 1999-2002, nine states reported 37 cases of pesticide illness related to pyrethroids used for WNV control, although the types of illnesses were not specified. Pyrethroids, primarily sumithrin, accounted for about 28% of all reported cases (CDC, 2003a). In New York City, ULV spraying with pyrethroids was not associated with population-level increases in rates of emergency-room visits for asthma in 1999-2000 (Karpati et al., 2004). Population-level health effect data following pyrethrin applications are not available. 7. What are the health risks of ULV spraying for WNV control? Who is at risk?

There is a small risk that people who have already been sensitized (are allergic) to
pyrethrins may have an allergic reaction, such as allergic contact dermatitis or
exacerbation of asthma, if they are re-exposed.
There is a small chance that people who are chemically sensitive may experience a
worsening of their chemically-related conditions if they are re-exposed.
There is a small chance that people with preexisting asthma or chronic respiratory
conditions may experience a worsening in these conditions if they are exposed.
Individuals in higher risk categories like those listed above should contact their local
mosquito control agency for additional information about local mosquito control
activities.
All individuals, especially pregnant women, should take simple precautions to avoid
exposure to pesticides, including those used in mosquito control.
Workers, especially mixers, loaders, and applicators of pesticide formulations, are at
greater risk for exposure to pesticides than the general public. Workers who are
exposed to these pesticides as a result of their regular tasks may experience health
effects such as nausea and skin, eye, and upper respiratory irritation (Gupta et al.,
1980). In order to minimize occupational exposure, employers should ensure that all
precautions specified on the pesticide label are followed.
8. How likely is it that the public will be exposed to pesticides used for WNV
spraying?
ULV technology, which uses very low doses of pesticides, and the practice of spraying between dusk and dawn, when most people are indoors, help to minimize exposure to these pesticides. Since the pesticides used are unstable in sunlight and air, they are rapidly degraded and it is unlikely that exposure will occur the day following spraying. Exposure to pesticides may occur if people are outdoors in an area while spraying is occurring. 9. Do the health risks justify ULV spraying with pesticides for WNV mosquito
control?

Although 80% of human WNV infections are mild and often clinically unapparent,
illnesses are potentially serious. The most common form of illness is WNV fever. The
clinical course of WNV fever ranges from a mild febrile illness of several days’ duration
to debilitating fatigue, aching, and weakness that may last for weeks or months (Hayes
et al., 2005). Approximately 1 in 150 infections results in severe neurological disease
with potential permanent sequelae. The spectrum of neurological disease includes
meningitis, encephalitis, and paralysis. Of these, encephalitis shows a marked
predilection for the elderly, while meningitis tends to be more prevalent in the young. In
2004, CDC reported 100 deaths out of 2539 cases in the US (3.9% case fatality rate)
(CDC, 2004).
Studies evaluating the effectiveness of WNV control have shown that ULV spraying for
mosquitoes in areas with high rates of human disease results in a decrease in the rates of
human infection immediately following ULV applications (DeFeyter, 2004; Nasci, 2004).
A public health analysis conducted by New York City Department of Health determined
that no significant adverse public health impacts would be expected from exposure to the
adulticides when applied for the purposes of mosquito control and that any effects would
likely be less than those of WNV (NYCDOH, 2001).
10. How can pesticide exposure be minimized?

Although mosquito control pesticides and the techniques used pose low risks, exposure
to pesticides should be minimized. Some common sense steps to help reduce possible
exposure to pesticides include:
• Pay attention to the local media for announcements about spraying and remain indoors during applications in the immediate area. • People who suffer from chemical sensitivities or feel spraying may aggravate a preexisting health condition, may consult their physician or local health department and take special measures to avoid exposure. • Close windows and turn off window-unit air conditioners when spraying is taking • Do not let children play near or behind truck-mounted applicators when they are
11. Who should be contacted if illness is suspected due to exposure to ULV
spraying?

Those who feel they have experienced illness due to pesticides used for ULV mosquito
control should:
• Call the Poison Control Center for immediate advice: (800) 222-1222. • Consult their health care providers. Physicians are required to report all suspected pesticide illness to the local health officer. Health officers are required to file a pesticide illness report for all reported suspected pesticide illnesses, including occupational pesticide illnesses (OEHHA 2005; CDHS, 2005b). Health care providers are now required to report pesticide illnesses to the local health officer using the Confidential Morbidity Report (CDHS, 2005c). State programs use these reports to conduct illness surveillance for a variety of conditions. Those with concerns about their pets should consult their veterinarian. California Department of Health Services September 2005 Agency for Toxic Substances Disease Registry (ATSDR). 2003. Toxicological profile for pyrethrins and pyrethroids. http://iier1.isciii.es/toxprofiles/tp155.pdf Beasley V. 2000. Comparative toxicology of mosquito control strategies. In, R.A. Cook (Ed.) Proceedings of the West Nile Virus Action Workshop, hosted by the Wildlife Conservation Society, and sponsored by the New York State Assembly. Tarrytown, NY. (January 19-21, 2000). Brody SA, Loriaux DL. Epidemic of gynecomastia among haitian refugees: exposure to an environmental antiandrogen. Endocr Pract. 2003; 9:370-5. Brown LM, Blair A, Gibson R, Everett GD, Cantor KP, Schuman LM, Burmeister LF, Van Lier SF, Dick F. Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. Cancer Res. 1990; 50:6585-91. Butler WH, Gabriel KL, Osimitz TG, Preiss FJ. Oncogenicity studies of piperonyl butoxide in rats and mice. Human Exper Toxicol. 1998; 17:323-30. California Department of Health Services (CDHS). 2005a. Vector Borne Disease Section. Overview of Mosquito Control Practices in California. http://westnile.ca.gov/mosquito_control.htm California Department of Health Services (CDHS). 2005b. Surveillance of Occupational Disease and Injury. Occupational Health Branch. Occupational Health Surveillance and Evaluation Section. http://www.dhs.ca.gov/ohb/OHSEP/Default.htm http://www.cwci.org/Graphics/physician.PDF California Department of Health Services (CDHS). 2005c. Confidential Morbidity Report. http://www.dhs.ca.gov/publications/forms/pdf/pm110.pdf California Department of Pesticide Regulation (CDPR). 2005 CDPR Database - Available Toxicology Summaries http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm Carlson JE, Villaveces JW. Hypersensitivity pneumonitis due to pyrethrum. Report of a case. JAMA. 1977; 237:1718-9. Centers for Disease Control and Prevention (CDC). Illnesses associated with use of automatic insecticide dispenser units--selected states and United States, 1986-1999. MMWR Morb Mortal Wkly Rep. 2000; 49:492-5. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4922a3.htm Centers for Disease Control and Prevention (CDC). Human Exposure to Mosquito-
Control Pesticides —Mississippi, North Carolina, and Virginia, 2002 and 2003. MMWR
Morb Mortal Wkly Rep. 2005; 54: 529-35.
Centers for Disease Control and Prevention (CDC). 2003a. Surveillance for acute
insecticide-related illness associated with mosquito-control efforts--nine states, 1999-
2002. MMWR Morb Mortal Wkly Rep. 2003; 52:629-34.
Centers for Disease Control and Prevention (CDC). 2003b. Second national report on
human exposure to environmental chemicals. Atlanta, GA: US Department of Health
and Human Services. CDC 2003. http://www.cdc.gov/exposurereport
Centers for Disease Control and Prevention (CDC). 2004 West Nile Virus Activity in the
United States. http://www.cdc.gov/ncidod/dvbid/westnile/surv&control.htm
Centers for Disease Control and Prevention (CDC). Third national report on human
exposure to environmental chemicals. NCEH Pub. No. 05-0570. 2005.
http://www.cdc.gov/exposurereport/3rd/
DeFeyter S. 2004 West Nile Virus Response in Mesa County, Colorado Mesa County
Health Department, Colorado. Session 6, Sixth National Conference on West Nile Virus
in the United States San Jose, California February 8-9, 2005.
http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_2005.htm
Ecobichon DJ, Davies J, Doull M, et al. Neurotoxic effects of pesticides. In The Effects
of Pesticides on Human Health. 1990. Baker SR and Wilkinson DF, Editors. Princeton,
NJ: Princeton Scientific Publishing Co. Pages 131-99.
Eil C and Nisula BC. The binding properties of pyrethroids to human skin fibroblast
androgen receptors and to sex hormone binding globulin. J Steroid Biochem. 1990;
35:409-414.
Franz TJ, Lehman PA, Franz SF, Guin JD. Comparative percutaneous absorption of
lindane and permethrin. Arch Dermatol. 1996;132:901-5.
Garey J, Wolff MS. Estrogenic and antiprogestagenic activities of pyrethroid
insecticides. Biochem Biophys Res Commun. 1998; 251:855-9.
Go V, Garey J, Wolff MS, Pogo BG. Estrogenic potential of certain pyrethroid
compounds in the MCF-7 human breast carcinoma cell line. Environ Health Perspect.
1999; 107:173-7.
Gupta SK, Pandya MK, Jani JP, Kashyap SK. Health risks in ultra-low-volume (ULV)
aerial spray of malathion for mosquito control. J Environ Sci Health B. 1980; 15:287-94.
Hayes EB, Sejvar JJ, Zaki SR, Lanciotti RS, Bode AV, Campbell GL. Virology, pathology, and clinical manifestations of West Nile virus disease. Emerg Infect Dis. 2005; 11:1174-9. He F, Wang S, Liu L, Chen S, Zhang Z, Sun J. Clinical manifestations and diagnosis of acute pyrethroid poisoning. Arch Toxicol. 1989; 63:54-8. Heudorf U and Angerer J. Metabolites of pyrethroid insecticides in urine specimens: current exposure in an urban population in Germany. Environ Health Perspect 2001;109:213–7. IARC. Overall Evaluations of Carcinogenicity to Humans As evaluated in IARC Monographs Volumes 1-88. http://www-cie.iarc.fr/monoeval/crthall.html (2004) http://www-cie.iarc.fr/htdocs/monographs/vol30/piperonylbutoxide.html (1983) Karpati AM, Perrin MC, Matte T, Leighton J, Schwartz J, Barr RG. Pesticide spraying for West Nile virus control and emergency department asthma visits in New York City, 2000. Environ Health Perspect. 2004; 112:1183-7. Kim IY, Shin JH, Kim HS, Lee SJ, Kang IH, Kim TS, Moon HJ, Choi KS, Moon A, Han SY. Assessing estrogenic activity of pyrethroid insecticides using in vitro combination assays. J Reprod Dev. 2004; 50:245-55. Knepper RG, Walker ED, Wagner SA, Kamrin MA, Zabik MJ. Deposition of malathion and permethrin on sod grass after single, ultra-low volume applications in a suburban neighborhood in Michigan. J Am Mosq Control Assoc. 1996; 12:45-51. Kolmodin-Hedman B, Swensson A, Akerblom M. Occupational exposure to some synthetic pyrethroids (permethrin and fenvalerate). Arch Toxicol. 1982; 50:27-33. Kunimatsu T, Yamada T, Ose K, Sunami O, Kamita Y, Okuno Y, Seki T, Nakatsuka I. Lack of (anti-) androgenic or estrogenic effects of three pyrethroids (esfenvalerate, fenvalerate, and permethrin) in the Hershberger and uterotrophic assays. Regul Toxicol Pharmacol. 2002; 35:227-37. Litchfield, M. L. H. Toxicity to Mammals. Pp. 114-115 in Leahey, J. P. (Ed.) The Pyrethroid Insecticides. Taylor & Francis, London and Philadelphia. 1985. 440 pp. Maekawa A, Onodera H, Furuta K, Tanigawa H, Ogiu T, Hayashi Y. Lack of evidence of carcinogenicity of technical-grade piperonyl butoxide in F344 rats: Selective induction of ileocaecal ulcers. Food Chem Toxicol. 1985; 23:675-82. Moore JC, Dukes JC, Clark JR, Malone J, Hallmon CF, Hester PG. Downwind drift and deposition of malathion on human targets from ground ultra-low volume mosquito sprays. J Am Mosq Control Assoc. 1993; 9:138-142. Nasci R. Vector control and West Nile virus in Fort Collins, Colorado 2003 Session 6 Fifth National Conference on West Nile Virus in the United States Denver, Colorado February 3-5, 2004. http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_2004.htm National Toxicology Program (NTP). Bioassay of Piperonyl Butoxide for Possible Carcinogenicity (CAS No. 51-0306). Technical Report No. 120. 1979. NPTN. Piperonyl Butoxide: Technical Fact Sheet. 2000. http://npic.orst.edu/factsheets/pbotech.pdf NYCDOH. New York City Department of Health and Mental Hygiene. Environmental
Impact Statement, Mosquito-Borne Disease Control Programs, July 2001.
http://www.ci.nyc.ny.us/html/doh/downloads/pdf/wnv/f3cpub.pdf
Office of Environmental Health Hazard Assessment (OEHHA). Pesticide illness surveillance and reporting. http://www.oehha.ca.gov/pesticides/programs/Pestrpt.html O’Malley M. Regulatory evaluation of the skin effects of pesticides. In Krieger R, Editor. Handbook of Pesticide Toxicology. 2001. Orlando FL: Academic Press. Pages 299-334. Penagos H, O'Malley M, and Maibach HI. Pesticide Dermatoses. 2001, Boca Raton, FL: CRC Press. Pages 101-105 Takahashi O, Oishi S, Fujitani T, Tanaka T, Yoneyama M. Chronic toxicity studies of piperonyl butoxide in F344 rats: Induction of hepatocellular carcinoma. Fund Appl Toxicol. 1994; 22:293-303. Takahashi O, Oishi S, Fujitani T, Tanaka T, Yoneyama M. Chronic toxicity studies of piperonyl butoxide in CD-1 mice: Induction of hepatocellular carcinoma. Toxicology. 1997; 124:95-103. United States Environmental Protection Agency (US EPA). OPP. 1999. Evaluation of the carcinogenic potential of pyrethrins. Cancer Assessment Document. United States Environmental Protection Agency (US EPA). 2002. Pesticides and Mosquito Control. http://www.epa.gov/pesticides/factsheets/pesticides4mosquitos.htm US EPA. 2004. Pyrethrins: Report of the Cancer Assessment Review Committee. Third Evaluation . OPP-2005-0043-0010. http://docket.epa.gov/edkpub/do/EDKStaffItemDetailView;jsessionid=E940D9EFD89989002984FA680928D8E2?objectId=090007d48075c538 Wagner SL. Allergy from pyrethrin or pyrethroid insecticides. J Agromed. 1994; 1:39-45. Wagner SL. Fatal asthma in a child after use of an animal shampoo containing pyrethrin. West J Med. 2000;173:86-7. Wax PM, Hoffman RS. Fatality associated with inhalation of a pyrethrin shampoo. J Toxicol Clin Toxicol. 1994; 32:457-60. Wester RC, Bucks DA, Maibach HI. Human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide. Food Chem Toxicol. 1994; 32:51-3.

Source: http://mmvca.net/Documents/SafetyofPesticidesusedtoControlAdultMosquitoes.pdf