Table 5.

Studies associating environmental/mixed pesticide exposure with urogenital abnormalities.

Studies	Association	Pesticide Tested	CAs Tested	Exposure Type	Exposure Assessment	Study Type/Sample Size	Confounding Factors
(Sharpe and Skakkebaek, 1993)	+/−	Diethylstilbestrol (DES)	Cryptorchidism Hypospadias	Environmental Pharmacological	Unspecified	Collection of Epidemiological Studies	Pregnancy Endogenous estrogen levels Use of synthetics Diet source of oestrogens Exposure to environmental oestrogenic chemicals Maternal Age
(Garcia-Rodriguez et al., 1996)	+	Unspecified/All	Cryptorchidism	Environmental	Use of 4-point scale in each municipality, according to total surface area under cultivation and predominant crops.	Ecological	Population of municipality cases and controls/age
(Skakkebaek et al., 2001)	+/−	Unspecified/All	Testicular dysgenesis syndrome	Environmental/Occupational	Unspecified	Collection of Epidemiological Studies	Embryonal programming and gonadal development during fetal life. Fertility Parental exposure
(Mamoulakis et al., 2002)	+	Unspecified/All	Cryptorchidism	Environmental	Three major pediatric center databases in Athens (Aghia Sophia Children’s Hospital, Aglaia Kyriakou Children’s Hospital and Pentelis Children’s Hospital	Retrospective epidemiological study/208,912 live-born boys	Seasonality by month of birth Maternal hCG profiles Low environmental temperature Daylight length
(Bianca et al., 2003)	+	Unspecified/All	Hypospadias	Unspecified/All	Towns with intense industrial (Augusta) and agricultural (Vittoria) activity compared to a commercial one (Catania)	Ecological	Parental age Gestational age Parity/number of previous spontaneous abortions Mode of delivery Birth weight Paternal occupation/paternal educational level
(Sharpe, 2003)	+	Oestrogens and oestrogenic chemicals	Testis cancer, cryptorchidism, hypospadias, low sperm counts	Environmental Pharmacological	Unspecified Interviews/Questionnaire	Collection of Epidemiological Studies	Maternal Age Low birth weight (Intra-uterine growth retardation) First pregnancy Impaired androgen production/action in fetal life Exposure during pregnancy
(Virtanen et al., 2005)	+	9 compounds	Testicular dysgenesis syndrome	Environmental/Occupational	The Turku University Central Hospital data GLOBOCAN 2000	Collection of clinical and epidemiological findings and biological and experimental studies	Karyotype Gestational age Birth weight Parental exposure
(Meyer et al., 2006)	+/−	38 compounds	Hypospadias	Environmental	Interviews/NASS data/Arkansas agricultural databases/usage guidelines published by University of Arkansas Cooperative Extension Service and the Southern Integrated Pest Management Center	Case-control/1081	Pregnancy Month when prenatal care began/number of previous births Exposure metric representing total pesticide use Maternal age Maternal race/paternal education Gestational age at birth Maternal pregnancy smoking/pregnancy weight gain
(Carbone et al., 2007)	+/−	Unspecified/All	Hypospadias/Cryptorchidism	Environmental/Occupational	Interviews/Job exposure matrix	Case-control/293	Birth weight Parental age/educational level Parity Contraceptives’ types used prior to pregnancy/parental genital tract pathologies/anti-abortion drugs use during pregnancy/smoking/alcohol consumption
(Brouwers et al., 2007)	+/−	Unspecified/All	Hypospadias	Unspecified/All	Mailed questionnaires	Case-control/834	Educational level/parental native country/+23 unspecified risk factors assessed
(Dugas et al., 2010)	+/−	Unspecified/All	Hypospadias	Environmental	Questionnaire-based telephone interviews	Case-control/961	Maternal smoking Maternal age Parental income Birth weight Previous stillbirth Folate intake during first 3 months of pregnancy
(Giordano et al., 2010)	+	HCB/DDE	Hypospadias	Occupational/Dietary	Interviews/Job exposure matrix/Questionnaires	Case-control/58	Maternal age/breastfeeding duration Percent of lipids in the serum
(Carmichael et al., 2013)	+	292 chemicals	Hypospadias	Environmental	Residence geocoding/Pesticide Use Reporting records	Case-control/2885	Maternal race/ethnicity Maternal age Infant birth year
(Agopian et al., 2013a)	+	Atrazine	All	Residential	US Geological Survey Data/AgroTrak surveys/Census of Agriculture and National Agriculture Statistics Service	Case-control/32,866	Season of conception Birth year Maternal age Race/ethnicity/education History of previous live births Birthplace Smoking
(Kalfa et al., 2015)	+	All EDCs	Hypospadias	Environmental/Occupational	Job history questionnaire completed by mothers.	Case-control/219 newborns	Job-exposure matrix Gestational age Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history)
(Mamoulakis et al., 2017)	+	Unspecified/All	Hypospadias	Environmental	Data on the population at risk were collected from the Hellenic Statistical Authority	Case-control/542	Intrauterine life: i) air temperature; ii) rainfall amount; iii) sunshine duration

CAs: Congenital Abnormalities; DDE: Dichlorodiphenyldichloroethylene; DDT: p,p′-Dichlorodiphenyltrichloroethane; EDs: Endocrine Disruptors; HCB: Hexachlorobenzene; HCH: Hexachlorocyclohexane; NASS: National Agricultural Statistics Service; OPs: Organophosphates; OR: Odds Ratio; RR: Relative Risk; VSDs: Ventricular Septal Defects; 95% CI: 95% Confidence Interval; +: association detected; −: no association detected; +/−: trend towards association (not statistically significant).