Table 2.

Studies regarding agricultural occupational pesticide exposure and other health outcomes: May 15, 2018 – May 14, 2019

Author	Participants	Exposures and Assessments	Outcomes and Assessments	Key Results (all confidence intervals at 95%)
DNA Damage and Oxidative Stress
Hutter HP et al. August 2018 [37]	38 pesticide sprayers and 33 farmers not exposed to pesticides from coffee production farms in the Dominican Republic	Pesticide sprayers were considered exposed, additional information was collected from a questionnaire on demographics and indicators of pesticide exposure including type and duration	Buccal cell samples analyzed for genotoxic and cytotoxic effects: micronuclei cells, total micronuclei, nuclear buds & broken eggs, binucleated cells, condensed chromatin, karyorrhectic cells, karyolitic cells, and pyknosis	Micronuclei cells: OR=3.098, CI 1.297 – 7.404 Total micronuclei: OR=2.534, CI 1.219 – 5.226 Nuclear buds & broken eggs: OR=1.916, CI 1.448 – 2.536 Binucleated cells: OR=1.412, CI 1.207 – 1.650
Kahl SVF et al. September 2018 [38]	121 tobacco farm workers occupationally exposed to pesticide mixtures and 121 non-exposed non-farm workers in Brazil	Those with an occupation as a tobacco farmer were considered exposed to pesticides and completed a questionnaire adapted from the International Commission for Protection against Environmental Mutagens and Carcinogens	Whole blood comet assay as well as buccal cell micronucleus cytome assay for damage index, micronucleus, nuclear buds, binucleated cells, and telomere length; blood cotinine levels and inorganic elements; thiobarbituric acid reactive substances (TBARS) and total equivalent antioxidant capacity (TEAC); and various polymorphisms	Increased frequency of: Damage index: 22.1 ± 1.6 (exposed) vs. 4.6 ± 0.4 (unexposed), p=<0.001 Micronucleus: 25.3 ± 2.9 (exposed) vs. 5.8 ± 0.7 (unexposed), p=<0.001 Nuclear buds: 3.3 ± 0.3 (exposed) vs. 1.1 ± 0.1 (unexposed), p=<0.001 Binucleated cells: 7.2 ± 0.5 (exposed) vs 5.4 ± 0.4 (unexposed), p=0.010 Exposed vs. non-exposed increased levels of oxidative stress biomarkers: TBARS: p=<0.001 TEAC: p=<0.001
Hayat K et al. November 2018 [39]	Pesticide industry workers (formulators and packers), pesticide sprayers, and controls with no occupational exposure to pesticides	Pesticide industry workers and sprayers were considered exposed to pesticides	Whole blood comet assay for tail length and comet frequency, pesticide residues in blood samples, and hepatic and nervous system enzymes	Tail length (μm): 16.88 ± 8.57 (industry workers) vs. 16.33 ± 3.78 (sprayers) vs. 6.53 ± 2.75 (controls), p=<0.01 Comet frequency: 17.56 ± 11.55 (industry workers) vs. 15.76 ± 9.37 (sprayers) vs. 3.25 ± 1.42 (controls), p=<0.01
Saad-Hussein A et al. February 2019 [40]	50 urban researchers using pesticides in laboratories, 50 rural pesticide sprayers, and 50 urban researchers not occupationally exposed to pesticides and 50 rural controls not occupationally exposed to pesticides	Urban researchers exposed to pesticides in laboratories and rural pesticide sprayers were considered exposed	Whole blood telomere length, telomerase activity, comet assay for tail length, percent DNA in tail, and tail moment; GST genotypes; liver tumor markers	Comet tail length: 17.84 ± 1.07 (rural exposed) vs. 8.4 ± 0.72 (rural controls), p=<0.0001 Percent DNA in tail: 4.57 ± 0.40 (rural exposed) vs. 0.84 ± 0.19 (rural controls), p=<0.0001 Tail moment: 0.73 ± 0.05 (rural exposed) vs. 0.08 ± 0.001 (rural controls), p=<0.0001
Dhananjayan V et al. March 2019 [41]	77 tea garden workers exposed to pesticide and 66 individuals with no occupational exposure to pesticides in India, recruited from December 2013 to February 2014	Women who had worked in tea gardens for at least 3 years were considered exposed to pesticides. Participants completed a questionnaire on demographics, health, lifestyle, and occupational details	Peripheral lymphocyte comet assay for percent DNA in tail, tail length, tail moment, and olive tail moment; and cholinesterase activity in erythrocytes and blood plasma	Mean tail length (μm): 9.45 ± 5.28 (exposed) vs. 2.09 ± 0.95 (unexposed), p=<0.05 Percent DNA in tail: 13.1 ± 8.17 (exposed) vs. 2.26 ± 1.63 (unexposed), p=<0.05 Tail moment (μm): 3.19 ± 2.29 (exposed) vs. 0.20 ± 0.12 (unexposed), p=<0.05 Olive tail moment (μm): 4.15 ± 2.18 (exposed) vs. 0.59 ± 0.44 (unexposed), p=<0.05
Intranuovo G et al. July 2018 [42]	22 agricultural workers exposed to pesticides and 24 non-agricultural hematologic outpatients from the provinces of Bari and Taranto, Italy	Agricultural workers were considered exposed to pesticides. Intensity level score for pesticide exposure calculated based on questionnaire responses regarding pesticide mixing, application, personal hygiene, use of protective equipment, repair of pesticide tanks, and use of tractors with cabins	Peripheral lymphocyte comet assay for tail moment, tail area, head DNA, tail DNA, integral intensity, head radius, tail length, olive movement, and head area	Odds of tail moment above 75th percentile in exposed to unexposed: OR=5.77, CI 4.63 – 7.21 Odds of tail length above 75th percentile in exposed to unexposed: OR=6.36, CI 5.1 – 7.95
Cattelan MDP et al. June 2018 [46]	84 farmers reporting occupational pesticide use and 68 farmers not reporting occupational pesticide use in Brazil	Farmers reporting pesticide use were considered exposed, based on a questionnaire regarding pesticide use and occupational practices	Blood samples to measure thiobarbituric acid reactive substances (TBARS) and carbonylation of proteins (Carbonyl); superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH), and glutathione peroxidase (GPx); and frequency of micronuclei in leukocytes	Micronuclei frequency: 0.24% (exposed) vs. 0.12% (unexposed), p=0.288 SOD activity: decreased in exposed vs. unexposed, p=< 0.01 GSH activity: decreased in exposed vs. unexposed, p=<0.01 GPx activity: decreased in exposed vs. unexposed, p=< 0.01 TBARS: decreased in exposed vs. unexposed, p=0.02
Sapbamrer R et al. May 2019 [47]	56 male farmers in Thailand	In-person interview on demographics and occupational exposures, and blood samples collected pre- and post-pesticide application seasons	Peripheral leukocyte comet assay for tail length and tail moment;, 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels; superoxide dismutase (SOD) activity	Median tail length (μm): 5.66 (pre-pesticide application season) vs. 5.67 (post-pesticide application season), p=0.867 Median tail moment (μm): 2.84 (pre-pesticide application season) vs. 2.83 (post-pesticide application season), p=0.729 Median 8-OHdG (ηg/mL): 8.31 (pre-pesticide application season) vs. 7.20 (post-pesticide application season), p=0.757 Median SOD (U/mL): 0.94 (pre-pesticide application season) vs. 1.35 (post-pesticide application season), p=< 0.001
Lozano-Paniagua D et al. October 2018 [51]	175 greenhouse workers carrying out farming activities (pruning, weeding, thinning, and applying pesticides) and 91 healthy individuals without occupational exposure to pesticides in Almeria, Spain	Greenhouse workers were considered exposed to pesticides. Analyses was conducted for two crop seasons: low pesticide exposure season (one to two pesticide applications per month) and high pesticide exposure season (weekly pesticide applications)	Blood samples to measure thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), and gamma-glutamyl transpeptidase (GGT) and Paraoxonase 1 (PON1)	Mean FRAS (μmol/l): High exposure season: 2.800 ± 0.017 (greenhouse workers) vs. 2.664 ± 0.020 (unexposed), p=< 0.001 Mean SHT (μmol/l): High exposure season: −0.250 ± 0.015 (greenhouse workers) vs. −0.396 ± 0.019 (unexposed), p=<0.001 Low exposure season: −0.366 ± 0.019 (greenhouse workers) vs. −0.387 ± 0.126 (unexposed), p=<0.001 Mean PON1 (U/l): High exposure season: 2.276 ± 0.036 (greenhouse workers) vs. 2.206 ± 0.047 (unexposed), p=0.069 Low exposure season: 2.231 ± 0.033 (greenhouse workers) vs. 2.115 ± 0.046 (unexposed), p=0.069
Neurological Disorders
Rohlman DS et al. May 2019 [66]	98 adolescents aged 12–21 years, comprised of 59 pesticide applicators working for the Ministry of Agriculture in Egypt and 39 non-applicators	Pesticide applicated were considered exposed to pesticides, measurements were also done for urinary 3,5,6-trichloro-2-pyridinol (TCPy) levels, a biomarker of chlorpyrifos exposure, and blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, biomarkers of organophosphate exposure	Symptoms of attention deficit hyperactivity disorder (ADHD) assessed by parental completion of the Revised Short Form of Conners’ Parent Rating Scale	ADHD symptoms: 4.46 ± 4.95 (applicators) vs. 1.44 ± 2.18 (non-applicators), p=<0 .001 Positive dose-response effect for number of ADHD symptoms and TCPy level: p=<0.001 Positive dose-response effect for number of ADHD symptoms and AChE: p=<0.001 Positive dose-response effect for number of ADHD symptoms and BChE: p=<0.001
Guytingco A et al. July 2018 [67]	6,118 agricultural workers in Thailand completing a questionnaire on occupational pesticide use and pesticide behavioral patterns, and symptoms, among those 3,431 providing a blood sample	Blood acetylcholinesterase (AChE) levels, a biomarker of organophosphate pesticide exposure	Self-reported symptoms of dizziness, dry skin & irritation, fatigue, burning sensation in nose, sore throat, cough, rash, sweating, headache, conjunctivitis, heart palpitations	12.5% of participants had low AChE levels; Prevalence of dizziness: 12.4% (abnormal AChE) vs. 4.0 % (normal AChE), p=<0.001 Prevalence of headache: 3.3% (abnormal AChE) vs. 1.3% (normal AChE), p=0.010 Prevalence dry skin and irritation: 10.5% (abnormal AChE) vs. 4.0% (normal AChE), p=<0.001
Serrano-Medina A et al. February 2019 [72]	140 agricultural workers and 100 individuals not exposed to pesticides in Mexico	Agricultural workers were considered exposed to pesticides, measurements were also done for blood acetylcholinesterase levels, a biomarker of organophosphate pesticide exposure	Symptoms of neuropsychiatric disorders as assessed by the Mini International Neuropsychiatric Interview Diagnostic Test (MINI)	Depression diagnosis frequency: 14.3% (exposed) vs. 3.0% (unexposed) Major depression with suicidal risk diagnosis frequency: 31.4% (exposed) vs. 8.0% (unexposed) Generalized anxiety diagnosis frequency: 14.3% (exposed) vs. 18.0% (unexposed) No psychiatric disorder diagnosis frequency: 36% (exposed) vs. 64% (unexposed) Positive association between AChE activity & psychiatric disorders such as suicide risk: p=0.006
Shrestha S et al. January 2019 [73]	Subset of the Agricultural Health Study (AHS) who completed the third AHS follow-up and met all study inclusion criteria: 11,232 pesticide applicators from North Carolina and Iowa	Self-reported experience of a high pesticide exposure event (HPEE)	Self-reported olfactory impairment	Olfactory impairment and: History of HPEE reported at enrollment: OR=1.49, CI 1.28 – 1.73 HPEE involving the respiratory or digestive track: OR=1.53, CI 1.22 – 1.92 HPEE involving dermal contact: OR=1.47, CI 1.22 – 1.78
Respiratory Effects
Buralli RJ et al. June 2018 [79]	48 farm workers in tomato cultivation in Brazil and 34 relatives residing in the same area who also may have helped in agricultural activities	Rural workers and relatives were considered exposed to pesticides, specifically 49 pesticides from 31 chemical groups based on self-reported use Crop season (active work in tomato cultivation) and off-season (not working in agriculture) were compared, blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was also measured	Self-reported respiratory symptoms based on the European Community Respiratory Health Survey (ECRHS) and spirometry testing	Crop season and: Wheeze or chest tightness: OR=2.25, CI 0.63 – 10 Wheeze with breathlessness: OR=0.67, CI 0.06 – 5.82 Wheeze without cold: OR=1.5, CI 0.17 – 17.96 Waking with chest tightness: OR=6, CI 0.73 – 275.99 Waking with cough: OR=5.5, CI 1.20 – 51.07 Nasal allergies and hay fever: OR=2.4, CI 0.79 – 8.70
Metabolic Effects
Park S et al. January 2019 [83]	Korea Farmers Cohort Study: 2,559 farmers and farm managers from rural areas of Wonju and Pyeongchang, Gangwon-do, Korea, recruited from 2005 – 2008	Intensity level [(mixing status + application method + repair status) × Personal Protective Equipment] and Cumulative Exposure Index (CEI) [intensity levelxduration (number of years) × frequency (average days per year)], from questionnaires on occupation as a farmer, mixing or applying pesticides, and specifics of pesticide use	Prevalence of diabetes defined by fasting plasma glucose ≥ 126 mg/dL, or 2-hour plasma glucose ≥ 200 mg/dL during oral glucose tolerance test, or HbAlc ≥ 6.5%, or reported current use of insulin or antidiabetic medication	Diabetes and: Ever pesticide use: OR=1.58, CI 1.13 – 2.21 ≥ 20 years of pesticide use: OR=1.51, CI 1.07 – 2.14 ≥ 10 days of pesticide use per year: OR=1.53, CI 1.09 – 2.15 Pesticide exposure at lower intensity level: OR=1.55, CI 1.07 – 2.24 Pesticide exposure at higher intensity level: OR=1.53, CI 1.06 – 2.22 Higher CEI: OR=1.54, CI 1.03 – 2.30
Kongtip P et al. November 2018 [84]	243 conventional farmers and 235 organic farmers in Thailand	Work as a conventional farmer was considered exposed, work as an organic farmer was considered non-exposed	Body mass index (BMI), waist circumference, percent body fat, blood pressure, metabolic syndrome, and blood sample analysis of serum glucose, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)	Conventional farm work to organic farm work: BMI: RR=1.83, CI 1.20 – 2.78 Waist circumference: RR=1.69, CI 1.13 – 2.51 Percent body fat: RR=1.31, CI 1.05 – 1.64 TGs: RR=1.51, CI 1.01 – 2.27 TC: RR=2.20, CI 1.69 – 2.86 LDL: RR=1.34, CI 1.14 – 1.57 HDL: RR=0.83, CI 0.37 – 0.95
Thyroid Effects
Shrestha S et al. Sept 2018 [89]	Subset of the Agricultural Health Study (AHS) who completed at least one follow-up survey between 1999 and 2016: 38,698 pesticide applicators from North Carolina and Iowa	Ever/never use of pesticides and intensity-weighted cumulative days of pesticide use based on self-administered questionnaires on farm life & agricultural practices, types of crops & livestock, and pesticide use/use of >50 individual pesticide active ingredients	Self-reported hypothyroidism	Hypothyroidism and: Ever use of chlordane: HR=1.21, CI 1.04 – 1.41 Ever use of diazinon: HR=1.27, CI 1.10 – 1.48 Ever use of dichlorvos: HR=1.42, CI 1.17 – 1.72 Ever use of malathion: HR=1.23, CI 1.04 – 1.46 Ever use of dicamba: HR=1.27, CI 1.08 – 1.50 Ever use of glyphosate: HR=1.28, CI 1.07 – 1.52 Ever use of 2,4-D: HR=1.30, CI 1.07 – 1.58
Bernieri T et al. March 2019 [91]	46 soybean growers and 27 individuals not exposed to pesticides an urban area of Brazil	Employment as a soybean grower was considered exposed to pesticides, blood butyrylcholinesterase (BChE) activity was also measured	Serum levels of free thyroxin (FT4), total triiodothyronine (TT3) and thyroid-stimulating hormone (TSH)	Activity of BChE (U/L): 7969.8 ± 1582.3 (exposed) vs. 9140.2 ± 2032.3 (unexposed) U/L, p=0.006 TT3 (ng/dL): 139.0 ± 28.6 (exposed) vs. 104.5 ± 20.0 (unexposed) ng/dL, p=<0.001 FT4 (ng/dL): 0.78 ± 0.15 (exposed) vs. 0.66 ± 0.09 (unexposed) ng/dL, p=<0.001 TSH (μUI/mL): 2.15 ± 1.09 (exposed) vs. 2.91 ± 1.35 (unexposed) μUl/mL, p=0.007