Pyrethroid epidemiology: a quality-based review

Figures & data

Table 1. Definition of ratings for study quality.

	Study parameters
Classification	Outcomes	Exposure metric	3-PBA* level	Study design
Strong	Measurement from a medical provider or a confirmed diagnosis	Occupational settings with multiple measurements Specific and repeated biomarker	Mean 3-PBA >1µg/l	Cohort, case control design
Neutral	Self-reported diseases, symptoms, test scores, >1 biological sample	Self-reported occupation, Single biomarker(s) with known source of exposure
Poor	Single sample of a short-lived chemical or hormone without considering error	Ecological (proximity to an application); Single biomonitoring sample without considering error	Mean 3-PBA ≤1μg/l	Cross-sectional

* 3-Phenoxybenzoic acid (3-PBA) is a metabolite of cypermethrin, deltamethrin and permethrin; compared to US 75th percentile.

Table 2. Male hormonal and reproductive effects.

Author, year of publication	Outcomes	Exposure metric	Mean 3-PBA (µg/l)	Study design
(A) Sperm quality; disruption in sperm genetic integrity
Bian et al. (2004)	Sperm characteristics (−) single sample	Fenvalerate factory workers (Ambient air, personal air, and dermal contamination) (+) occupational setting	NA	(−) Cross Sectional
Imai et al. (2014)	Sperm characteristics (−) single sample	Urinary metabolite 3-PBA (–) spot sample	0.8	(−) Cross sectional
Ji et al. (2011)	Sperm characteristics (−) single sample	Urinary metabolite 3-PBA (−) spot sample	1.1	(−) Cross sectional
Jurewicz et al. (2016)	Y:X ratio in sperm	Urinary metabolites (3-PBA, cis-/trans-DCCA) (−) spot sample	0.2	(−) Cross sectional
Kamijima et al. (2004)	Sperm characteristics (summer and winter)	Sprayer (Self-reported occupational use of pesticides)	NA	(−) Cross sectional
Lifeng et al. (2006)(note often cited as Tan L)	Sperm characteristics (−) single sample	Fenvalerate factory workers (Ambient air, personal air, and dermal contamination) (+) occupational setting	NA	(−) Cross sectional
Meeker et al. (2008), Young et al. (2013)	Sperm characteristics Chromosome disomy (−) single sample	Urinary metabolites (3-PBA, cis/trans-DCCA) (−) spot sample	0.2	(−) Cross sectional
Perry et al. (2007)	Sperm characteristics (−) single sample	Urinary metabolites (3-PBA, cis/trans-DCCA, and cis-DBCA) (−) spot sample	1.2	(−) Cross sectional
Jurewicz et al. (2015), Radwan et al. (2014)	Sperm characteristics, DNA damage (−) single sample	Urinary metabolites (3-PBA, cis-/trans-DCCA, 4F3PBA, and cis-DBCA) (−) spot sample	0.2	(−) Cross sectional
Radwan et al. (2015)	Chromosome disomy	Urinary metabolites (3-PBA, cis-/trans-DCCA, 4F3PBA, and cis-DBCA) (−) spot sample	0.2	(−) Cross sectional
Toshima et al. (2012)	Sperm characteristics (−) single sample	Urinary metabolite 3-PBA (−) spot sample	0.5	(−) Cross sectional
Xia et al. (2004)	Sperm characteristics (−) single sample	Fenvalerate factory workers (Ambient air, personal air, and dermal contamination) (+) occupational setting	NA	(−) Cross sectional
Xia et al. (2008)	Sperm characteristics (−) single sample	Urinary metabolite 3-PBA (−) spot sample	1.3	(−) Cross sectional
(B) Male hormone levels
Han et al. (2008)	Hormones (LH, FSH, testosterone, prolactin) (−) single sample	Urinary metabolite 3-PBA (−) spot sample	1.4	(−) Cross sectional
Kamijima et al. (2004)	Hormones (LH, FSH, testosterone, prolactin) (summer and winter)	Sprayers (−) Self-reported occupational use of pesticides, not specific to pyrethroids	NA	(−) Cross sectional
Meeker et al. (2009)	Hormones (LH, FSH, testosterone, prolactin, SHBG, inhibin B) (−) single sample	Urinary metabolites (3-PBA, cis/trans-DCCA) (−) spot sample	0.2	(−) Cross sectional
Radwan et al. (2014)	Hormones (FSH, estradiol testosterone) (−) single sample	Urinary metabolites (3-PBA, cis/trans-DCCA, 4F3PBA, and cis-DBCA) (−) spot sample	0.2	(−) Cross sectional
Yoshinaga et al. (2014)	Hormones (LH, FSH, testosterone, prolactin, SHBG, inhibin B) (−) single sample	Urinary metabolite 3-PBA (−) spot sample	0.8	(−) Cross sectional
(C) Fertility
Sallmen et al. (2003)	Self-reported time to pregnancy	Occupational exposure as a greenhouse worker (−) analyzes of specific pesticides (self-reported) not conducted		(+) Cohort
Whitworth et al. (2015)	Serum levels of anti-Mullerian hormone (−) single sample	Spray for mosquitos in home (for malaria), self-reported (−) Actual internal exposure to pyrethroid was not confirmed, nor was spraying with pyrethroid		(−) Cross sectional

Follicle stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding protein (SHBG).

Table 3. Adverse outcomes at birth and in childhood.

Author, year of publication	Outcomes	Exposure metric	Mean 3-PBA (µg/l)	Study design
(A) Infant health at birth
Berkowitz et al. (2004)	Infant birth weight, birth length, head circumference and gestational age	Maternal urine at third trimester Metabolite 3-PBA (−) spot sample	18.3	(+) Cohort Note: While this is a prospective design, the samples were collected late in pregnancy.
Ding et al. (2015)	Infant birth weight, birth length, head circumference and gestational age	Maternal urine at delivery (3-PBA, cis-/trans-DCCA, 4F3PBA, and cis-DBCA) (−) spot sample	0.5 (geometric mean)	(−) Cross sectional
Hanke et al. (2003)	Infant birth weight	Self-reported occupation in farming and pesticides used (−) PYR exposure unconfirmed	NA	(+) Cohort
Kennedy et al. (2005)	Infant birth weight, spontaneous abortion, major malformations	Self-reported use of NIX for lice during pregnancy	NA	(+) Cohort
Mytton et al. (2007)	Infant birth weight, birth length and gestational age, other pregnancy outcomes	Treatment with permethrin for scabies during pregnancy	NA	(+) Cohort
Neta et al. (2010, 2011)	Infant birth weight, birth length, head circumference and gestational age	Cord blood, cis/trans permethrin (−) spot sample	NA	(−) Cross sectional
Ostrea et al. (2009, 2012)	Infant birth weight, birth length, head circumference and gestational age	Pyrethroids in serum (maternal and cord), hair (maternal and infant), meconium (−) spot sample	NA	(−) Cross sectional
Zhang et al. (2013, 2014)	Infant birth weight, birth length, head circumference and gestational age	Maternal urine at third trimester Metabolite 3-PBA (−) spot sample	0.4	(+) Cohort Note: While this is a prospective design, the samples were collected late in pregnancy.
(B) Birth defects
Carmichael et al. (2014, 2016)	Congenital heart defects, 5 additional birth defects	Pesticide application near maternal residence (−) ecological indicator	NA	(+) Case control
Meyer et al. (2006)	Urogenital birth defects	Pesticide application near maternal residence (−) ecological indicator	NA	(+) Case control
(C) Developmental delay and autism spectrum disorder (in utero exposure)
Horton et al. (2011)	Bayley MDI, PDI (36 months)	Cis/trans permethrin and piperonyl butoxide in air and serum cis/trans permethrin (maternal and cord blood) (−) spot sample	NA	(+) Cohort; Part of the CCCEH
Ostrea et al. (2012, 2014)	Griffiths Development Screen Test (24 months)	Pyrethroids in serum (maternal and cord), hair (maternal and infant), meconium (−) spot sample	NA	(+) Cohort
Shelton et al. (2014)	Developmental delay and autism spectrum disorders (3–5 years)	Pesticide application near maternal residence (−) ecological indicator	NA	(+) Case control
Xue et al. (2013)	Development Screen Test (12 months)	Maternal urine at unknown stage of pregnancy (3-PBA, cis/trans-DCCA) (−) spot sample (−) Note: This is a poorly described study, limiting the interpretation of the results.	2.2	(+) Cohort
(D) Developmental delay and autism spectrum disorder (childhood exposure)
Domingues et al. (2016)	Autism spectrum disorder	Urinary metabolite 3-PBA (−) spot sample	>1 per Figure	(−) Cross sectional
Fiedler et al. (2015)	A battery of neurobehavioral tests was conducted using computers and trained examiners. Ages 6–8	Urinary metabolites (DCCA, 3-PBA) Two community groups were evaluated rice farming and aquaculture. Both groups were expected to be exposed to pyrethroids due to mosquito control.	Means >2.5	(−) Cross sectional
Lu et al. (2009)	Computerized test battery	Urinary metabolite 3-PBA 2 spot samples	< 0.1	(−) Cross sectional
Oulhote and Bouchard (2013)	Self-reported by parent using the Strengths and Difficulties Questionnaire (SDQ) Ages 6–11	Urinary metabolites (3-PBA, cis/trans-DCCA, 4F3PBA, and cis-DBCA) (−) spot sample	0.2	(−) Cross sectional
Quiros-Alcala et al. (2014)	Self-reported by parent [Learning disability (LD) and attention deficit disorder (ADHD] Ages 6–15	Urinary metabolites [3-PBA and cis/trans-DCCA] (−) spot sample.	0.3	(−) Cross sectional
Wagner-Schuman et al. (2015)	Self-reported by parent using a structured diagnostic interview for ADHD (DSM-IV) Ages 8–15	Urinary metabolite 3-PBA (−) spot sample	0.3	(−) Cross sectional
Viel et al. (2015)	Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Age 6	Maternal urine (prenatal) and the child (age 6) (3-PBA,4F3PBA, cis-/trans-DCCA, and cis-DBCA. (−) spot samples	Prenatal: <LOD Child: 0.02	Cohort, including cross sectional analyzes
Gunier et al. (2016)	Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Age 7	Maternal residence during pregnancy within 1 km of an application. (−) ecological indicator.	NA	(+) Case control

Table 4. Respiratory outcomes.

Author, year of publication	Outcomes	Exposure metric	Study design
(A) Cough, wheeze or asthma in the child (maternal exposure)
Liu et al. (2012)	Wheeze, cough, asthma (reported by mother) Serum IgE (age 5)	Personal air samples of cis/trans permethrin, PBO (prenatal); residential air samples (age 5–6) (−) spot sample (−) poor correlation of PYR exposure estimates (personal air, serum, residential air)	(+) Cohort; including cross sectional analyzes, part of the CCCEH
Reardon et al. (2009)	Wheeze, cough, asthma (reported by mother) Serum IgE (age 5)	Prenatal personal air samples of cis/trans permethrin in CCCEH (−) spot sample	(+) Cohort, including cross sectional analyzes, part of the CCCEH
(B) Cough, wheeze or asthma (adult exposure)
Karpati et al. (2004)	Emergency room visit for asthma	Use of pyrethroid to control mosquitos by zip code (−) ecological exposure to home owner	(−) Cross sectional ecological
Mwanga et al. (2016)	Self-reported asthma, Serum cytokines	Urine samples of 3-PBA,4F3PBA, cis/trans-DCCA, and cis-DBCA. (−) spot sample Note: Exposure to pyrethroids were higher than NHANES in both rural and urban groups.	(−) Cross sectional
Quansah et al. (2016)	Self-reported cough, wheeze, phlegm production	Urine samples of lambda cyhalothrin, cypermethrin (−) spot samples	(−) Cross sectional
Hoppin et al. (2002)	Self-reported wheeze	Self-reported use in applicators Permethrin (crops); Permethrin (poultry)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2006b)	Self-reported wheeze	Self-reported use in commercial applicators Permethrin (crops); Permethrin (poultry)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2006a)	Self-reported wheeze	Self-reported use in private and commercial applicators Permethrin (crops); Permethrin (poultry)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2007a)	Self-reported farmers Lung (hypersensitivity pneumonitis)	Self-reported use in private applicators and spouses Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2007b)	Self-reported chronic bronchitis	Self-reported use in private applicators Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS
Valcin et al. (2007)	Self-reported chronic bronchitis	Self-reported use in nonsmoking spouses of applicators Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2008)	Self-reported asthma	Self-reported use in women of the AHS: Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS
Hoppin et al. (2016)	Self-reported wheeze (allergic and non-allergic)	Self-reported use in applicators interviewed in 2005–2010 8 pyrethroids	(−) Cross sectional analyzes, part of the AHS
Slager et al. (2009)	Self-reported rhinitis	Self-reported use in commercial applicators Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS
Slager et al. (2010)	Self-reported rhinitis	Self-reported use in the AHS: Permethrin (crops); Permethrin (animals)	(−) Cross sectional analyzes, part of the AHS

Table 5. Adult exposure leads to effects on the immune system.

Author, year of publication	Outcomes	Exposure metrics	Mean 3-PBA (µg/L)	Study design
Costa et al. (2013)	Hematological blood tests and cytokines	First morning urine (3-PBA) only confirm exposure in greenhouse workers	7.8 μg/g cr.	(−) Cross-sectional
Costa et al. (2014)	Lymphocytes and natural killer cells	Urine sample (PYR) to confirm exposure in workers and controls (−) Effects were only evaluated by group, not by exposure to specific pesticides, and not to pyrethroids.	NA	(−) Cross-sectional
Mwanga et al. (2016)	Self-reported asthma, serum cytokines	Urine samples of 3-PBA,4F3PBA, cis/trans-DCCA, and cis-DBCA. (−) spot sample	3.85 μg/g cr (rural) 3.32 μg/g cr (urban)	(−) Cross sectional.
Neta et al. (2010, 2011)	Serum cytokines	Cord blood, cis/trans permethrin (−) spot sample	NA	(−) Cross sectional

Table 6. Cancer and genotoxicity.

Author, year of publication	Outcomes	Exposure metrics	Study design
(A) Cancer in adults
Rusiecki et al. (2009)	All cancers	Self-reported use in applicators Permethrin (crops) Permethrin (animals)	(+) Cohort, part of the AHS
Alavanja et al. (2014)	NHL, MM and other subtypes	Self-reported use in applicators Permethrin (crops) Permethrin (animals)	(+) Cohort, part of the AHS
Koutros et al. (2010)	Chromosome 8q24 and prostate cancer	Self-reported use in applicators Permethrin (crops) Permethrin (animals)	(+) Cohort, part of the AHS
(B) Cancer in children
Ding et al. (2012)	Acute lymphocytic leukemia	Urine samples (3-PBA, 4F3PBA, cis/trans-DCCA, and cis-DBCA. (−) spot sample 3-PBA geometric mean <1 μg/L	(−) Cross-sectional analyzes of cancer and pyrethroid urine levels
Ferreira et al. (2013)	Acute lymphocytic leukemia, acute myeloid leukemia	Self-report by the mother (−) There may have been some recall bias among the case mothers, being more likely to report pesticide use	(+) Case control
Malagoli et al. (2016)	Childhood leukemia	Residence, land use and pesticide registers (−) ecological indicators, not specific to pyrethroid	(+) Case control
(C) Genotoxicity
Costa et al. (2014)	Genotoxic (DNA damage, micronucleus, chromosomal aberrations)	Urine sample (“PYR”) to confirm exposure in workers and controls (−) Effects were only evaluated by group, not by exposure to specific pesticides, and not to pyrethroids.	(−) Cross sectional
Hou et al. (2013)	Telomere length as measured in buccal cells	Self-reported use in 1234 applicators: Permethrin (crops) Permethrin (animals)	(+) Cohort, part of the AHS
Kasiotis et al. (2012)	Genotoxic (DNA damage)	Blood sample (cypermethrin, deltamethrin) to confirm exposure before and after applications (−) The effects were only evaluated as pre/post, not by exposure to specific pesticides, and not to pyrethroids.	This is a study of 19 applicators, using a before/after design.
Ogut et al. (2011)	Superoxide dismutase (SOD) as an indicator of oxidative stress	Working in apple and cherry production (−) The effects were evaluated by workers and control, not by exposure to specific pesticides, and not to pyrethroids	(−) Cross-sectional

Table 7. Concordance of epidemiological and toxicological evidence.

Category	Epidemiology outcomes	Evidence in animal studies
Table 2: Male hormonal and reproductive effects	(A) Sperm quality and/or a disruption in sperm genetic integrity.	There is limited evidence for effects by individual pyrethroids on testosterone and sperm parameters. Reproduction studies indicate no effects on fertility. As a class, pyrethroids are not likely to affect hormonal levels or reproductive capability.
	(B) Male hormone levels.
	(C) Decreased fertility.
Table 3: Adverse outcomes at birth and in childhood	(A) Adverse infant health	Pyrethroids do not cause developmental toxicity in guideline studies. The USEPA analysis of individual pyrethroids and as a class did not indicate potential harm to the fetus or post-natal development.
	(B) Birth defects.
	(C) Developmental delay and autism spectrum disorder (exposure in utero)
	(D) Developmental delay and autism spectrum disorder (exposure in childhood)
Table 4: Respiratory outcomes	(A) Respiratory outcomes (exposure in utero)	USEPA has indicated that their review does not show a connection between pyrethroid exposure and asthma. Given the paresthetic characteristics of pyrethroids, stimulation of cough from acute, single inhalation exposure is biologically plausible, but this symptom is not an allergic reaction and is not related to asthma.
	(B) Respiratory outcomes (Childhood exposure)
Table 5: Immune system	Immune system.	No immunological effects have been noted in animal studies that support the registrations of pyrethroids.
Table 6: Cancer and genotoxicity	(A) Cancer in Adults	There is limited evidence for some pyrethroids (cypermethrin, permethrin, and bifenthrin). For these three, liver and/or lung were affected at very high doses. All other pyrethroids were not carcinogenic. There is no consistent evidence for genotoxicity for any of the pyrethroids.
	(B) Cancer in Children
	(C) Genotoxicity

Bian Q, Xu LC, Wang SL, Xia YK, Tan LF, Chen JF, Song L, Chang HC, Wang XR. 2004. Study on the relation between occupational fenvalerate exposure and spermatozoa DNA damage of pesticide factory workers. Occup Environ Med. 61:999–1005.

 PubMed Web of Science ®Google Scholar

Imai K, Yoshinaga J, Yoshikane M, Shiraishi H, Mieno MN, Yoshiike M, Nozawa S, Iwamoto T. 2014. Pyrethroid insecticide exposure and semen quality of young Japanese men. Reprod Toxicol. 43:38–44.

 PubMed Web of Science ®Google Scholar

Ji G, Xia Y, Gu A, Shi X, Long Y, Song L, Wang S, Wang X. 2011. Effects of non-occupational environmental exposure to pyrethroids on semen quality and sperm DNA integrity in Chinese men. Reprod Toxicol. 31:171–176.

 PubMed Web of Science ®Google Scholar

Jurewicz J, Radwan M, Sobala W, Radwan P, Jakubowski L, Wielgomas B, Ligocka D, Brzeznicki S, Hanke W. 2016. Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio. Environ Pollut. 213:732–740.

 PubMed Web of Science ®Google Scholar

Kamijima M, Hibi H, Gotoh M, Taki K, Saito I, Wang H, Itohara S, Yamada T, Ichihara G, Shibata E, et al. 2004. A survey of semen indices in insecticide sprayers. J Occup Health. 46:109–118.

 PubMed Web of Science ®Google Scholar

Lifeng T, Shoulin W, Junmin J, Xuezhao S, Yannan L, Qianli W, Longsheng C. 2006. Effects of fenvalerate exposure on semen quality among occupational workers. Contraception. 73:92–96.

 PubMed Web of Science ®Google Scholar

Meeker JD, Barr DB, Hauser R. 2008. Human semen quality and sperm DNA damage in relation to urinary metabolites of pyrethroid insecticides. Hum Reprod. 23:1932–1940.

 PubMed Web of Science ®Google Scholar

Young HA, Meeker JD, Martenies SE, Figueroa ZI, Barr DB, Perry MJ. 2013. Environmental exposure to pyrethroids and sperm sex chromosome disomy: a cross-sectional study. Environ Health. 12:111.

 PubMed Web of Science ®Google Scholar

Perry MJ, Venners SA, Barr DB, Xu X. 2007. Environmental pyrethroid and organophosphorus insecticide exposures and sperm concentration. Reprod Toxicol. 23:113–118.

 PubMed Web of Science ®Google Scholar

Jurewicz J, Radwan M, Wielgomas B, Sobala W, Piskunowicz M, Radwan P, Bochenek M, Hanke W. 2015. The effect of environmental exposure to pyrethroids and DNA damage in human sperm. Syst Biol Reprod Med. 61:37–43.

 PubMed Web of Science ®Google Scholar

Radwan M, Jurewicz J, Wielgomas B, Sobala W, Piskunowicz M, Radwan P, Hanke W. 2014. Semen quality and the level of reproductive hormones after environmental exposure to pyrethroids. J Occup Environ Med. 56:1113–1119.

 PubMed Web of Science ®Google Scholar

Radwan M, Jurewicz J, Wielgomas B, Piskunowicz M, Sobala W, Radwan P, Jakubowski L, Hawula W, Hanke W. 2015. The association between environmental exposure to pyrethroids and sperm aneuploidy. Chemosphere. 128:42–48.

 PubMed Web of Science ®Google Scholar

Toshima H, Suzuki Y, Imai K, Yoshinaga J, Shiraishi H, Mizumoto Y, Hatakeyama S, Onohara C, Tokuoka S. 2012. Endocrine disrupting chemicals in urine of Japanese male partners of subfertile couples: a pilot study on exposure and semen quality. Int J Hyg Environ Health. 215:502–506.

 PubMed Web of Science ®Google Scholar

Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X. 2004. Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate. Toxicology. 203:49–60.

 PubMed Web of Science ®Google Scholar

Xia Y, Han Y, Wu B, Wang S, Gu A, Lu N, Bo J, Song L, Jin N, Wang X. 2008. The relation between urinary metabolite of pyrethroid insecticides and semen quality in humans. Fertil Steril. 89:1743–1750.

 PubMed Web of Science ®Google Scholar

Han Y, Xia Y, Han J, Zhou J, Wang S, Zhu P, Zhao R, Jin N, Song L, Wang X. 2008. The relationship of 3-pba pyrethroids metabolite and male reproductive hormones among non-occupational exposure males. Chemosphere. 72:785–790.

 PubMed Web of Science ®Google Scholar

Meeker JD, Barr DB, Hauser R. 2009. Pyrethroid insecticide metabolites are associated with serum hormone levels in adult men. Reprod Toxicol. 27:155–160.

 PubMed Web of Science ®Google Scholar

Yoshinaga J, Imai K, Shiraishi H, Nozawa S, Yoshiike M, Mieno MN, Andersson AM, Iwamoto T. 2014. Pyrethroid insecticide exposure and reproductive hormone levels in healthy Japanese male subjects. Andrology. 2:416–420.

 PubMed Web of Science ®Google Scholar

Sallmen M, Liesivuori J, Taskinen H, Lindbohm ML, Anttila A, Aalto L, Hemminki K. 2003. Time to pregnancy among the wives of Finnish greenhouse workers. Scand J Work Environ Health. 29:85–93.

 PubMed Web of Science ®Google Scholar

Whitworth KW, Baird DD, Steiner AZ, Bornman RM, Travlos GS, Wilson RE, Longnecker MP. 2015. Anti-Mullerian hormone and lifestyle, reproductive, and environmental factors among women in rural South Africa. Epidemiology. 26:429–435.

 PubMed Web of Science ®Google Scholar

Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, Lapinski RH, Godbold JH, Holzman IR, Wolff MS. 2004. In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect. 112:388–391.

 PubMed Web of Science ®Google Scholar

Ding G, Cui C, Chen L, Gao Y, Zhou Y, Shi R, Tian Y. 2015. Prenatal exposure to pyrethroid insecticides and birth outcomes in rural northern China. J Expo Sci Environ Epidemiol. 25:264–270.

 PubMed Web of Science ®Google Scholar

Hanke W, Romitti P, Fuortes L, Sobala W, Mikulski M. 2003. The use of pesticides in a polish rural population and its effect on birth weight. Int Arch Occup Environ Health. 76:614–620.

 PubMed Web of Science ®Google Scholar

Kennedy D, Hurst V, Konradsdottir E, Einarson A. 2005. Pregnancy outcome following exposure to permethrin and use of teratogen information. Am J Perinatol. 22:87–90.

 PubMed Web of Science ®Google Scholar

Mytton OT, Mcgready R, Lee SJ, Roberts CH, Ashley EA, Carrara VI, Thwai KL, Jay MP, Wiangambun T, Singhasivanon P, et al. 2007. Safety of benzyl benzoate lotion and permethrin in pregnancy: a retrospective matched cohort study. BJOG. 114:582–587.

 PubMed Web of Science ®Google Scholar

Neta G, Goldman LR, Barr D, Sjödin A, Apelberg BJ, Witter FR, Halden RU. 2010. Distribution and determinants of pesticide mixtures in cord serum using principal component analysis. Environ Sci Technol. 44:5641–5648.

 PubMed Web of Science ®Google Scholar

Neta G, Goldman LR, Barr D, Apelberg BJ, Witter FR, Halden RU. 2011. Fetal exposure to chlordane and permethrin mixtures in relation to inflammatory cytokines and birth outcomes. Environ Sci Technol. 45:1680–1687.

 PubMed Web of Science ®Google Scholar

Ostrea EM, Bielawski DM, Posecion NC, Corrion M, Villanueva-Uy E, Bernardo RC, Jin Y, Janisse JJ, Ager JW. 2009. Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides. Environ Res. 109:116–122.

 PubMed Web of Science ®Google Scholar

Ostrea EM, Reyes A, Villanueva-Uy E, Pacifico R, Benitez B, Ramos E, Bernardo RC, Bielawski DM, Delaney-Black V, Chiodo L, et al. 2012. Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age. Neurotoxicology. 33:669–675.

 PubMed Web of Science ®Google Scholar

Zhang J, Hisada A, Yoshinaga J, Shiraishi H, Shimodaira K, Okai T, Noda Y, Shirakawa M, Kato N. 2013. Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women. Environ Res. 127:16–21.

 PubMed Web of Science ®Google Scholar

Zhang J, Yoshinaga J, Hisada A, Shiraishi H, Shimodaira K, Okai T, Koyama M, Watanabe N, Suzuki E, Shirakawa M, et al. 2014. Prenatal pyrethroid insecticide exposure and thyroid hormone levels and birth sizes of neonates. Sci Total Environ. 488–489:275–279.

 PubMed Web of Science ®Google Scholar

Carmichael SL, Yang W, Roberts E, Kegley SE, Padula AM, English PB, Lammer EJ, Shaw GM. 2014. Residential agricultural pesticide exposures and risk of selected congenital heart defects among offspring in the San Joaquin Valley of California. Environ Res. 135:133–138.

 PubMed Web of Science ®Google Scholar

Carmichael SL, Yang W, Roberts E, Kegley SE, Brown TJ, English PB, Lammer EJ, Shaw GM. 2016. Residential agricultural pesticide exposures and risks of selected birth defects among offspring in the San Joaquin Valley of California. Birth Defects Res A Clin Mol Teratol. 106:27–35.

 PubMed Web of Science ®Google Scholar

Meyer KJ, Reif JS, Veeramachaneni DN, Luben TJ, Mosley BS, Nuckols JR. 2006. Agricultural pesticide use and hypospadias in eastern Arkansas. Environ Health Perspect. 114:1589–1595.

 PubMed Web of Science ®Google Scholar

Horton MK, Rundle A, Camann DE, Boyd Barr D, Rauh VA, Whyatt RM. 2011. Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment. Pediatrics. 127:e699–e706.

 PubMed Web of Science ®Google Scholar

Ostrea EM, Villanueva-Uy E, Bielawski D, Birn S, Janisse JJ. 2014. Trends in long term exposure to propoxur and pyrethroids in young children in the Philippines. Environ Res. 131:13–16.

 PubMed Web of Science ®Google Scholar

Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, Hansen RL, Hertz-Picciotto I. 2014. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 122:1103–1109.

 PubMed Web of Science ®Google Scholar

Xue Z, Li X, Su Q, Xu L, Zhang P, Kong Z, Xu J, Teng J. 2013. Effect of synthetic pyrethroid pesticide exposure during pregnancy on the growth and development of infants. Asia Pac J Public Health. 25:72S–79S.

 PubMed Web of Science ®Google Scholar

Domingues VF, Nasuti C, Piangerelli M, Correia-Sa L, Ghezzo A, Marini M, Abruzzo PM, Visconti P, Giustozzi M, Rossi G, et al. 2016. Pyrethroid pesticide metabolite in urine and microelements in hair of children affected by autism spectrum disorders: a preliminary investigation. Int J Environ Res Public Health. 13:388.

 PubMed Web of Science ®Google Scholar

Fiedler N, Rohitrattana J, Siriwong W, Suttiwan P, Ohman Strickland P, Ryan PB, Rohlman DS, Panuwet P, Barr DB, Robson MG. 2015. Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children. Neurotoxicology. 48:90–99.

 PubMed Web of Science ®Google Scholar

Lu C, Essig C, Root C, Rohlman DS, Mcdonald T, Sulzbacher S. 2009. Assessing the association between pesticide exposure and cognitive development in rural Costa Rican children living in organic and conventional coffee farms. Int J Adolesc Med Health. 21:609–621.

 PubMedGoogle Scholar

Oulhote Y, Bouchard MF. 2013. Urinary metabolites of organophosphate and pyrethroid pesticides and behavioral problems in Canadian children. Environ Health Perspect. 121:1378–1384.

 PubMed Web of Science ®Google Scholar

Quiros-Alcala L, Mehta S, Eskenazi B. 2014. Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. Children: NHANES 1999-2002. Environ Health Perspect. 122:1336–1342.

 PubMed Web of Science ®Google Scholar

Wagner-Schuman M, Richardson JR, Auinger P, Braun JM, Lanphear BP, Epstein JN, Yolton K, Froehlich TE. 2015. Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U.S. Children. Environ Health. 14:44.

 PubMed Web of Science ®Google Scholar

Viel JF, Warembourg C, Le Maner-Idrissi G, Lacroix A, Limon G, Rouget F, Monfort C, Durand G, Cordier S, Chevrier C. 2015. Pyrethroid insecticide exposure and cognitive developmental disabilities in children: the PELAGIE mother-child cohort. Environ Int. 82:69–75.

 PubMed Web of Science ®Google Scholar

Gunier RB, Bradman A, Harley KG, Kogut K, Eskenazi B. 2016. Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Environ Health Perspect. 125:057002.

 Google Scholar

Liu B, Jung KH, Horton MK, Camann DE, Liu X, Reardon AM, Perzanowski MS, Zhang H, Perera FP, Whyatt RM, et al. 2012. Prenatal exposure to pesticide ingredient piperonyl butoxide and childhood cough in an urban cohort. Environ Int. 48:156–161.

 PubMed Web of Science ®Google Scholar

Reardon AM, Perzanowski MS, Whyatt RM, Chew GL, Perera FP, Miller RL. 2009. Associations between prenatal pesticide exposure and cough, wheeze, and IgE in early childhood. J Allergy Clin Immunol. 124:852–854.

 PubMed Web of Science ®Google Scholar

Karpati AM, Perrin MC, Matte T, Leighton J, Schwartz J, Barr RG. 2004. Pesticide spraying for west Nile virus control and emergency department asthma visits in New York City, 2000. Environ Health Perspect. 112:1183–1187.

 PubMed Web of Science ®Google Scholar

Mwanga HH, Dalvie MA, Singh TS, Channa K, Jeebhay MF. 2016. Relationship between pesticide metabolites, cytokine patterns, and asthma-related outcomes in rural women workers. Int J Environ Res Public Health. 13:E957.

 PubMed Web of Science ®Google Scholar

Quansah R, Bend JR, Abdul-Rahaman A, Armah FA, Luginaah I, Essumang DK, Iddi S, Chevrier J, Cobbina SJ, Nketiah-Amponsah E, et al. 2016. Associations between pesticide use and respiratory symptoms: a cross-sectional study in southern Ghana. Environ Res. 150:245–254.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, London SJ, Alavanja MC, Sandler DP. 2002. Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study. Am J Respir Crit Care Med. 165:683–689.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, London SJ, Lynch CF, Alavanja MC, Sandler DP. 2006b. Pesticides associated with wheeze among commercial pesticide applicators in the Agricultural Health Study. Am J Epidemiol. 163:1129–1137.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, London SJ, Lynch CF, Alavanja MC, Sandler DP. 2006a. Pesticides and adult respiratory outcomes in the Agricultural Health Study. Ann N Y Acad Sci. 1076:343–354.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, Kullman GJ, Henneberger PK, London SJ, Alavanja MC, Sandler DP. 2007a. Pesticides and other agricultural factors associated with self-reported farmer's lung among farm residents in the Agricultural Health Study. Occup Environ Med. 64:334–341.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MC, Sandler DP. 2007b. Pesticide use and chronic bronchitis among farmers in the Agricultural Health Study. Am J Ind Med. 50:969–979.

 PubMed Web of Science ®Google Scholar

Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MC, Sandler DP, Hoppin JA. 2007. Chronic bronchitis among nonsmoking farm women in the Agricultural Health Study. J Occup Environ Med. 49:574–583.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, London SJ, Henneberger PK, Kullman GJ, Alavanja MC, Sandler DP. 2008. Pesticides and atopic and nonatopic asthma among farm women in the Agricultural Health Study. Am J Respir Crit Care Med. 177:11–18.

 PubMed Web of Science ®Google Scholar

Hoppin JA, Umbach DM, Long S, London SJ, Henneberger PK, Blair A, Alavanja M, Beane Freeman LE, Sandler DP. 2016. Pesticides are associated with allergic and non-allergic wheeze among male farmers. Environ Health Perspect. 125:535–543.

 Google Scholar

Slager RE, Poole JA, Levan TD, Sandler DP, Alavanja MC, Hoppin JA. 2009. Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study. Occup Environ Med. 66:718–724.

 PubMed Web of Science ®Google Scholar

Slager RE, Simpson SL, Levan TD, Poole JA, Sandler DP, Hoppin JA. 2010. Rhinitis associated with pesticide use among private pesticide applicators in the Agricultural Health Study. J Toxicol Environ Health A. 73:1382–1393.

 PubMed Web of Science ®Google Scholar

Costa C, Rapisarda V, Catania S, Di Nola C, Ledda C, Fenga C. 2013. Cytokine patterns in greenhouse workers occupationally exposed to alpha-cypermethrin: an observational study. Environ Toxicol Pharmacol. 36:796–800.

 PubMed Web of Science ®Google Scholar

Costa C, García-Lestón J, Costa S, Coelho P, Silva S, Pingarilho M, Valdiglesias V, Mattei F, Dall'armi V, Bonassi S, et al. 2014. Is organic farming safer to farmers' health? A comparison between organic and traditional farming. Toxicol Lett. 230:166–176.

 PubMed Web of Science ®Google Scholar

Rusiecki JA, Patel R, Koutros S, Beane-Freeman L, Landgren O, Bonner MR, Coble J, Lubin J, Blair A, Hoppin JA, et al. 2009. Cancer incidence among pesticide applicators exposed to permethrin in the Agricultural Health Study. Environ Health Perspect. 117:581–586.

 PubMed Web of Science ®Google Scholar

Alavanja MC, Hofmann JN, Lynch CF, Hines CJ, Barry KH, Barker J, Buckman DW, Thomas K, Sandler DP, Hoppin JA, et al. 2014. Non-Hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the Agricultural Health Study. PLoS One. 9:e109332.

 PubMed Web of Science ®Google Scholar

Koutros S, Beane Freeman LE, Berndt SI, Andreotti G, Lubin JH, Sandler DP, Hoppin JA, Yu K, Li Q, Burdette LA, et al. 2010. Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer. Cancer Res. 70:9224–9233.

 PubMed Web of Science ®Google Scholar

Ding G, Shi R, Gao Y, Zhang Y, Kamijima M, Sakai K, Wang G, Feng C, Tian Y. 2012. Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in Shanghai. Environ Sci Technol. 46:13480–13487.

 PubMed Web of Science ®Google Scholar

Ferreira JD, Couto AC, Pombo-De-Oliveira MS, Koifman S. 2013. In utero pesticide exposure and leukemia in Brazilian children <2 years of age. Environ Health Perspect. 121:269–275.

 PubMed Web of Science ®Google Scholar

Malagoli C, Costanzini S, Heck JE, Malavolti M, Girolamo GD, Oleari P, Palazzi G, Teggi S, Vinceti M. 2016. Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community. Int J Hyg Environ Health. 219:742–748.

 PubMed Web of Science ®Google Scholar

Hou L, Andreotti G, Baccarelli AA, Savage S, Hoppin JA, Sandler DP, Barker J, Zhu ZZ, Hoxha M, Dioni L, et al. 2013. Lifetime pesticide use and telomere shortening among male pesticide applicators in the Agricultural Health Study. Environ Health Perspect. 121:919–924.

 PubMed Web of Science ®Google Scholar

Kasiotis KM, Kyriakopoulou K, Emmanouil C, Tsantila N, Liesivuori J, Souki H, Manakis S, Machera K. 2012. Monitoring of systemic exposure to plant protection products and DNA damage in orchard workers. Toxicol Lett. 210:182–188.

 PubMed Web of Science ®Google Scholar

Ogut S, Gultekin F, Kisioglu AN, Kucukoner E. 2011. Oxidative stress in the blood of farm workers following intensive pesticide exposure. Toxicol Ind Health. 27:820–825.

 PubMed Web of Science ®Google Scholar