Skip to main content
. 2022 Sep 29;130(9):096002. doi: 10.1289/EHP9934

Table 3.

Characteristics of Latin American and the Caribbean studies on pesticide exposure and neurobehavioral outcomes published between 2007 and 2021 (n=54).

Study Year of publication/country Population and sample size Study design Pesticides assessed Exposure assessment method Pesticide or metabolite concentrations Health effect and assessment method/instrument Results
Studies on OCs
 Studies in children
  1. Torres-Sánchez et al.107 2007/Mexico 244 mother–child (0–12 months of age) pairs from malaria-endemic zone Prospective cohort OCs Maternal serum DDE before and during each trimester of pregnancy Geometric mean±geometric SD (GSD) (ng/mL):
p,p-DDE: first trimester=6.4±2.8; second trimester=6.8±2.9; third trimester=7.8±2.8
Neurodevelopment: mental and psychomotor development (BSID-II) Higher DDE during first trimester of pregnancy was associated with lower PDI scores in first year of life (β per 2-fold increase in DDE=0.5; 95% CI: 1.0, 0.1). Null associations between DDE and MDI scores.
  2. Torres-Sánchez et al.108 2009/Mexico 270 mother–child (12–30 months of age) pairs Prospective cohort OCs Maternal serum DDE during each trimester of pregnancy Mean±SD (ng/mL):
p,p-DDE: first trimester=6.3±3.1; second trimester=6.5±3.0; third trimester=7.9±2.8; p,p-DDT: first trimester=0.008±2.7; second trimester=0.006±2.0; third trimester=0.006±2.3
Neurodevelopment: mental and psychomotor development (BSID-II) Null associations of prenatal DDE with PDI and MDI scores.
  3. Bahena-Medina et al.109 2011/Mexico 265 mother–child (1 month of age) pairs Prospective cohort OCs Maternal serum DDE during each trimester of pregnancy Geometric mean±geometric SD (GSD) DDE (ng/mL):
First trimester: normal reflexes=6.2±3.1; one abnormal reflex=7.1±2.6; 2; abnormal reflexes=5.4±3.2; non-neurological soft signs=6.0±3.0; one neurological soft sign=7.0±2.9; 2 neurological soft signs=5.2±2.2
Second trimester: normal reflexes=7.5±2.8; one abnormal reflex=7.3±3.1; 2 abnormal reflexes=4.2±2.9; non-neurological soft signs=6.4±3.1; one neurological soft sign=7.8±2.9; 2 neurological soft signs=5.4±2.0
Third trimester: normal reflexes=7.5±2.7; one abnormal reflex=8.1±2.9; 2 abnormal reflexes=5.1±3.3; non-neurological soft signs=7.7±2.8; one neurological soft sign=7.0±3.1; 2 neurological soft signs=4.3±2.2
Neurodevelopment: neonatal reflexes (NBAS), neurological soft signs (Graham-Rosenblith scale), mental and psychomotor development (BSID) Null associations between prenatal DDE exposure and neonatal neurodevelopment.
  4. Dallaire et al.110 2012/Guadeloupe 153 mother–child (7 months of age) pairs living near banana plantations Prospective cohort OCs (chlordecone) Questionnaire (infant dietary intake history)
Cord blood chlordecone
Breast milk chlordecone at 3 months
Mean±SD chlordecone (μg/L):
Cord blood=0.53±1.97; breast milk=1.09±1.15
Neurodevelopment: visual recognition, memory, and processing speed (FTII, TAC, Brunet-Lezine scale) Those in the highest tertile of cord blood chlordecone concentrations (classified as concentrations>median) scored lower on the novelty preference test (β=0.2; 95% CI: 0.4, 0) than those in the second tertile of cord chlordecone concentrations (classified as concentrations>LOD and median) (β=0.1; 95% CI: 0.3, 0.1). Detectable concentrations of chlordecone in cord blood were associated with increased odds of low fine motor scores (OR=1.3; 95% CI: 1.1, 1.5).
  5. Boucher et al.111 2013/Guadeloupe 141 mother–child (18 months of age) pairs living near banana plantations Prospective cohort OCs (chlordecone) Questionnaire (infant dietary intake history)
Cord blood chlordecone
Breast milk chlordecone at 3 months
Mean±SD chlordecone (μg/L):
Cord blood=0.41±0.6; breast milk=0.93±0.90
Neurodevelopment: personal–social, communication, problem-solving, fine motor, and gross motor (ASQ-19) Higher chlordecone concentrations in cord blood were associated with lower fine motor scores among boys (β=0.32; p=0.03).
  6. Torres-Sánchez et al.112 2013/Mexico 203 mother–child (42–60 months of age) pairs Prospective cohort OCs Maternal serum DDE during each trimester of pregnancy Median (P10–P90) (ng/g lipid):
DDE: first trimester=1,255.40(259.264,964.21); second trimester=1,138.16(154.392,857.14); third trimester=812.75(153.232,919.00); DDT: first trimester=0.0123(0.012331.48); second trimester=0.0123(0.1232.54); third trimester=0.0123(0.1234.21)
Neurodevelopment: verbal, perceptual performance, quantitative, memory, motor skills, and general cognitive index (MSCA) Higher DDE during third trimester of pregnancy was associated with poorer verbal (β per 2-fold increase in DDE=1.1; 95% CI: 2.2, 0.1), quantitative (β=2.1; 95% CI: 3.2, 1.0), and memory (β=1.3; 95% CI: 2.2, 0.3) skills and a poorer general cognitive index (β=2.0; 95% CI: 3.6, 0.4) at 42–60 months of age.
  7. Osorio-Valencia et al.113 2015/Mexico 167 mother–child (60 months of age) pairs Prospective cohort OCs Maternal serum DDE during each trimester of pregnancy Mean±SD p,p-DDE (ng/g lipid):
First trimester: female=1,624±1,376; male=1,997±2,266; second trimester: female=1,297±1,194; male=1,424±1,494; third trimester: female=1,434±1,457; male=1,121±1,280
Neurodevelopment: lateralization and spatial orientation (MSCA) Higher DDE during second trimester of pregnancy was associated with poorer spatial orientation (β per 2-fold increase in DDE=0.2; 95% CI: 0.4, 0.04).
  8. Campos et al.118 2015/Brazil 46 children (6–16 years of age) Cross-sectional OCs Child serum HCH, HCB, DDE, DDT, endosulfan, aldrin, endrin, dieldrin, methoxychlor, and mirex Median (range) (ng/mL):
α-HCH=3.75(<LOD20,558.86); β-HCH=7.09(<LOD33,088.2); γ-HCH=2.03(<LOD5,160.83); p,p-DDT=3.98(<LOD5,300.06); o,p-DDT=0.50(<LOD2,145.75); p,p-DDE=6.63(<LOD33,556.54); p,p-DDD=1.06(<LOD803.79); aldrin=3.17(<LOD2,090.23); endrin=1.71(<LOD1,476.47); dieldrin=0.89(<LOD4,161.32); endosulfan 1=0.57(<LOD2.49); endosulfan 2=0.29(<LOD2.53); mirex=0.51(<LOD879.11); methoxychlorLOD (<LOD1.43)
Neurodevelopment: cognitive function (WISC-III) Higher α-HCH was associated with poorer performance IQ (β per 1 ng/mL increase =0.5; 95% CI: 0.9, 0), resistance to distraction (β=0.3; 95% CI: 0.6, 0), and processing speed (β=0.5; 95% CI=0.9, 0.1). Higher γ-HCH was associated with poorer resistance to distraction (β=1.7; 95% CI=3.1, 0.4) and processing speed (β=1.8; 95% CI=3.6, 0). Higher p,p-DDT was associated with poorer processing speed (β=0.8; 95% CI=1.4, 0.3).
  9. Cordier et al.117 2015/Guadeloupea 75 mother–child (18 months of age) pairs Prospective cohort OCs Cord blood and breast milk chlordecone, cord blood DDE Median (P25–P75) (μg/L) in entire study population (111 mother–child pairs):
Cord blood chlordecone=0.13(<LOD0.31); cord blood p,p-DDE=0.30(0.091.05); breast milk chlordecone=0.60(<LOD1.16)
Neurodevelopment: personal–social, communication, problem-solving, fine motor, and gross motor (ASQ-19) Association between cord chlordecone and fine motor scores among boys (reported by Boucher et al.111) was not mediated by TSH.
  10. Ogaz-Gonzales et al.114 2018/Mexico 142 mother–child (42–60 months of age) pairs Prospective cohort OCs Questionnaire (pesticide use history)
Maternal serum DDE during first and third trimester of pregnancy
Mean (P10–P90) DDE (ng/mL):
First trimester=7.6(<1.823.1)
Second trimester=8.1(1.323.5)
Third trimester=9.0(1.729.2)
Neurodevelopment: verbal, perceptual performance, quantitative, memory, motor skills, and general cognitive index (MSCA) Higher third-trimester maternal DDE was associated with lower motor development in children whose mothers had lower intake of DHA (an omega-3 fatty acid) (β per 2-fold increase in DDE=1.3; 95% CI: 2.6, 0.1), but not in children whose mothers had a higher DHA intake. Higher maternal DDE was associated with poorer memory skills in children whose mothers had lower ARA (an omega-6 fatty acid) intake (β per 2-fold increase in DDE=1.3; 95% CI: 2.3, 0.3) but not in children whose mothers had a higher ARA intake.
  11. Saint-Amour et al.115 2020/Guadeloupe 285 mother–child (7–8 years of age) pairs Prospective cohort OCs (chlordecone) Cord blood and child (7 years of age) blood chlordecone Median (range) chlordecone (μg/L):
Cord blood=0.80(0.0629.78); child blood=0.17(0.027.01)
Neurodevelopment: visual contrast sensitivity (FrACT) Higher cord plasma chlordecone (continuous) was associated with lower scores (β=0.1; 95% CI: 0.1, 0). Child chlordecone (continuous) was associated with lower scores among boys (β=0.1; 95% CI: 0.2, 0).
  12. Cordier et al.116 2020/Guadeloupe 116 mother–child (7 years of age) pairs Prospective cohort OCs (chlordecone) Cord blood and child (7 years of age) blood chlordecone Median (range) chlordecone (μg/L):
Cord blood=0.17(<LOD7.4); child blood=0.04(<LOD1.0)
Neurodevelopment: sex-typed play behavior (feminine, masculine, or neutral play reported as a proportion of the complete playing time) Null associations of cord blood and child chlordecone with sex-typed play behavior.
 Studies in adults
  13. Steenland et al.119 2014/Costa Rica 89 adults from historically (and now partially) agricultural area Cross-sectional OCs Questionnaire (occupational exposure history)
Serum HCH, DDE, DDT, and dieldrin
Mean±SD (ng/mL):
Past occupational pesticides exposure: p,p-DDE=0.7±0.55; p,p-DDT=0.14±0.08; dieldrin=7.58±19.63; β-HCH=0.78±0.30
No past occupational pesticides exposure: p,p-DDE=1.20±1.46; p,p-DDT=0.12±0.12; dieldrin=3.40±6.48; β-HCH=0.73±0.19
Neurodegeneration: spatial and temporal orientation, short-term memory, attention, calculation, language, praxis (MMSE); tremor-at-rest (UPDRS) Null associations of serum OC (parent compounds or metabolites) with MMSE and tremor-at-rest.
Studies on OPs or CBs
 Studies in children
  14. Handal et al.130 2007/Ecuador 142 children (24–61 months of age) from 2 communities with industrial flower farms and from a community with local agriculture and crops for food Cross-sectional CBs, OPs Questionnaire (parental occupational and residential exposure history, child outdoor activities) Not applicable Neurodevelopment: communication, fine motor, gross motor, problem-solving, personal–social (ASQ), visual–motor skills (Beery-Buktenica VMI developmental test) Maternal employment in the flower industry at time of child assessment was associated with improved communication (%change=6.9; 95% CI: 0.3, 8.5) and problem-solving (%change=8.4; 95% CI: 0.7, 9.4) skills. Pesticide use on domestic crops was also associated with better gross motor (%change=8.1; 95% CI: 0.6, 9.2) and personal–social (%change=7.0; 95% CI: 0.7, 9.0) scores, whereas pesticide use within the home was associated with lower communication scores (%change=7.5; 95% CI: 8.8, 0.3). Children who played with irrigation water had lower fine motor (%change=8.2; 95% CI: 9.3, 0.5) and problem-solving (%change=7.3; 95% CI: 8.4, 0.4) scores.
  15. Handal et al.121 2007/Ecuador 154 children (3–61 months of age) from 2 communities with industrial flower farms/129 children from a community with local agriculture and crops for food Cross-sectional CBs, OPs Questionnaire (parental occupational and residential exposure history) Not applicable Neurodevelopment: communication, fine motor, gross motor, problem solving, personal–social (ASQ) Children 3–23 months of age from industrial flower farms communities had lower gross motor (β=8.8, p=0.002), fine motor (β=5.0, p=0.06), and socioindividual (β=5.8, p=0.02) scores compared with children from a local agriculture community. Children 24–61 months of age from industrial flower farms communities had lower gross motor scores compared with children of similar ages from a local agriculture community (β=3.8, p=0.06).
  16. Handal et al.120 2008/Ecuador 121 children (3–23 months of age) from 2 communities with industrial flower farms and from a community with local agriculture and crops for food Cross-sectional CBs, OPs Questionnaire (maternal occupational exposure history during pregnancy) Not applicable Neurodevelopment: communication, fine motor, gross motor, problem solving, personal–social (ASQ), prehension and visual acuity (targeted development tests) Children whose mothers worked as floriculturists during pregnancy had lower communication (β=4.6; 95% CI: 9.6, 0.3) and fine motor β=8.0; 95% CI: 13.0, 3.1) scores and had an increased risk of poor visual acuity (OR=4.7; 95% CI: 1.1, 20) than children whose mothers did not.
  17. Harari et al.123 2010/Ecuador 84 children (6–8 years of age) living in a floricultural area Cross-sectional OPs Questionnaire (parental occupational and residential exposure history)
Urinary DAPsb
Blood AChEb
Not applicable Neurodevelopment: simple motor speed (finger tapping task), motor coordination (Santa Ana Form Board), attention (CPT), short-term auditory memory (WISC and Stanford-Binet), visual performance (Raven’s test and Stanford-Binet copying test), visual memory (Stanford-Binet copying recall test) Children whose mothers were exposed to pesticides during pregnancy showed poorer motor speed (β=7.1; 95% CI: 12.5, 1.6), motor coordination (OR=5.3; 95% CI: 1.03, 27.6), visual performance (Raven’s test: β=0.5; 95% CI: 0.2, 1.0), and visual memory (OR=6.6; 95% CI: 1.02, 42.9) compared with children of unexposed mothers. Children whose fathers were exposed to pesticides during pregnancy showed poorer visual memory (OR=13.4; 95% CI: 1.8, 101.9) than children of unexposed fathers. Children with current exposure (i.e., at least one detectable urinary DAP metabolite) had longer reaction times compared with children with no exposure (β=64.7; 95% CI: 12.4, 141.7).
  18. Muñoz-Quesada et al.127 2011/Chile 25 children (6–11 years of age) from rural communities Cross-sectional OPs Child urinary DAPs Geometric mean (range) (μg/L):
DMP=7.3(2.563.6); DMTP=7.0(2.551.4); DEP=17.3(2.549.9)
Neurodevelopment: cognitive function (WISC-III) Negative association between urinary DMTP and processing speed (r=0.44, p=0.01). Null associations of other DAP metabolites and WISC-III outcomes.
  19. Martos-Mula et al.129 2013/Argentina 42 children (7–10 years of age) living in an agricultural area/29 children living in a nonagricultural area Cross-sectional OPs, CBs Questionnaire
Blood AChE, BChE
Not applicable Neurodevelopment: associative memory (Digit and Symbol subtest), short-term memory (Digit Memory test), maze test (motor, visuospatial processing), cognitive function (WISC-III), gross motor and balance tests Children living in an agricultural area had poorer motor function and visuospatial processing than children living in a nonagricultural area (p<0.01). Null associations between enzyme activities and neurodevelopmental outcomes.
  20. Suarez-Lopez et al.122 2013/Ecuador 307 children (4–9 years of age) living in floricultural communities Cross-sectional OPs Questionnaire (parental occupational and residential exposure history)
Blood AChE
Not applicable Neurodevelopment: attention and inhibitory control, language, memory and learning, sensorimotor, visuospatial processing (NEPSY-II) Boys, but not girls, in the highest tertile of AChE activity had increased odds of poor neurodevelopment (< 9th percentile) than boys in the lowest tertile (total neurodevelopment OR=5.1; 95% CI: 0.8, 31.5; attention/executive functioning OR=4.6; 95% CI: 1.2, 17.4); memory/learning OR=6.0; 95% CI: 1.2, 31.1).
  21. Fortenberry et al.128 2014/Mexico 187 mother–child (6–11 years of age) pairs Prospective cohort OPs (chlorpyrifos) Maternal urinary TCPy during third trimester of pregnancy Geometric mean (P10–P90) TCPy (ng/mL): 1.76 (0.45–6.40) Neurodevelopment: attention and hyperactivity (CRS-R, CPT, BASC-2) Increased ADHD index for the highest TCPy tertile compared with the lowest tertile for boys (β=5.6; 95% CI: 0.2, 11.3). Increased attention problems for the middle TCPy tertile compared with the lowest tertile for girls (β=5.8; 95% CI: 0.8, 12.4).
  22. Suarez-Lopez et al.126 2017/Ecuador 308 children (4–9 years of age) living in floricultural communities Cross-sectional OPs Questionnaire (parental occupational and residential exposure history)
Blood AChE
Not applicable Neurodevelopment: attention and inhibitory control, language, memory and learning, sensorimotor, visuospatial processing (NEPSY-II) Children examined sooner after Mother’s Day had lower attention/inhibitory control (score difference per 10.8 d =0.4; 95% CI. 0.10, 0.7), visuospatial processing (0.6; 95% CI: 0.3, 0.9), and sensorimotor (0.4; 95% CI: 0.1, 0.8) scores than children examined later. Further adjustment for AChE activity had overall a small effect on most associations but strengthened associations in the attention and inhibitory control domain by about 16%.
  23. Suarez-Lopez et al.124 2019/Ecuador 529 adolescents (11–17 years of age) living in floricultural communities Cross-sectional OPs Blood AChE Not applicable Mental health disorders: anxiety (MASC-2) and depression symptoms (CDI-2) Lower AChE activity was associated with more depression symptoms (β per SD decrease in AChE activity=1.1; 95% CI: 0, 2.2). Associations were stronger among girls (β=1.6; 95% CI: 0.1, 3.1) than boys (β=0.7; 95% CI: 0.9, 2.3) and among younger (β=1.6; 95% CI: 0.2, 3.4) than older children (β=0.6; 95% CI: 0.8, 2.0). No associations were observed with anxiety scores.
  24. Suarez-Lopez et al.125 2021/Ecuador 300 adolescents (11–17 years of age) living in floricultural communities Cross-sectional OPs Blood AChE Not applicable Mental health disorders: anxiety (MASC-2) and depression symptoms (CDI-2) Lower AChE activity was associated with more depression symptoms (β per 10% decrease in AChE activity=1.0; 95% CI: 0, 1.9) and increased odds of an elevated depression score (OR=1.7; 95% CI: 1.0, 2.7). These associations were stronger among girls than boys. Adjustment for cortisol, testosterone and dehydroepiandrosterone reduced gender differences by 18%–62%.
 Studies in adults
  25. Wesseling et al.136 2010/Costa Rica 78 male banana farmworkers with poisoning/130 non-poisoned workers from company payrolls Cross-sectional OPs, CBs Questionnaire (occupational exposure history, history of OP pesticide poisoning)
Blood AChEb
Not applicable Mental health disorders: psychological distress and suicidal ideation (BSI) Farmworkers with history of OP pesticide poisonings had increased odds of somatization (OR=3.1; 95% CI:1.6, 6.0), obsessive-compulsiveness (OR=3.2; 95% CI:1.6, 6.2), interpersonal sensitivity (OR=2.9; 95% CI:1.5, 5.8), depression (OR=2.4; 95% CI: 1.3, 4.7), hostility (OR=2.3; 95% CI: 1.1, 4.6), anxiety (OR=2.3; 95% CI:1 1.4, 4.4), phobia (OR=1.9; 95% CI: 1.0, 3.6), and psychoticism (OR=2.2; 95% CI: 1.1, 4.3). Individuals with history of OP pesticide poisonings had increased odds of having suicidal thoughts in the previous month (OR=3.6; 95% CI: 1.5, 8.8), with increasing risk for those with more poisonings (PR=5.0; 95% CI: 1.7, 14.5). Farmworkers with history of CB pesticide poisonings had increased odds of somatization (OR=2.6; 95% CI: 1.1, 6.2).
  26. Muñoz-Quezada et al.132 2016/Chile 93 farmworkers/84 controls Cross-sectional OPs Questionnaire (occupational exposure history) Not applicable Neurobehavioral performance: cognitive function (WAIS-IV), visuospatial memory and visual perception (ROCF), visual memory and visuoconstruction skills (BVRT), neurological alterations with frontal involvement (MMSE), and motor performance Farmworkers had lower WAIS-IV verbal comprehension (β=3.2; 95% CI: 6.1, 0.2), processing speed (β=4.4; 95% CI: 8.6, 0.3), and total IQ (β=4.0; 95% CI: 6.8, 0.7) scores than controls. Farmworkers also had lower MMSE scores (β=1.0; 95% CI: 1.7, 0.1) and poorer discrimination sensitivity (β=1.0; 95% CI: 0.2, 1.2) and deep reflexes (β=1.1; 95% CI: 0.0, 2.2) than controls.
  27. Corral et al.131 2017/Chile 32 farmworkers/32 individuals living in agricultural communities/38 controls Cross-sectional OPs Questionnaire (occupational exposure history) Not applicable Neurobehavioral performance: spatial and temporal orientation, short-term memory, attention, calculation, language, praxis (MMSE), memory and attention (WAIS-R DST), visuoconstruction skills and visual memory (ROCF), divided attention and resistance to interference (Stroop), attention (d2), executive function (FAB), and verbal fluency (Barcelona for Animals and Letter P) Both farmworkers and people living in agricultural communities had increased odds of poorer (i.e., below cutoff value) executive function (OR=44.9; 95% CI: 5.6, 359.7 and OR=7.3; 95% CI: 1.7, 32.4, respectively), memory and attention (DST forward: OR=4.9; 95% CI: 1.6, 14.9, and DST backward: OR=7.4; 95% CI: 2.4, 22.4; DST forward: OR=4.5; 95% CI: 1.4, 13.8, and DST backward: OR=2.9; 95% CI: 1.02, 8.3, respectively), and verbal fluency (animals: OR=5.7; 95% CI: 1.3, 25.6, and Letter P: OR=16.7; 95% CI: 4.3, 64.6; animals: OR=4.5; 95% CI: 1.04, 19.4, and Letter P: OR=8.1; 95% CI: 2.1, 31.3, respectively) than the unexposed group.
  28. Grillo Pizarro et al.135 2018/Chile 55 farmworkers/58 unexposed controls Cross-sectional OPs Questionnaire (occupational and residential exposure history) Not applicable Peripheric polyneuropathy Farmworkers exposed to OP pesticides had increased odds of peripheric polyneuropathy compared with controls (OR=3.6; 95% CI: 1.2, 10.5)
  29. Serrano-Medina et al.137 2019/Mexico 140 farmworkers/100 controls Cross-sectional OPs Questionnaire (occupational exposure history)
Blood AChE
Not applicable Mental health disorders: neuropsychiatric disorders (MINI based on DSM-IV) Farm work was associated with increased odds of suicide (OR=5.3; 95% CI: 2.4, 11.9), whereas higher AChE activity levels were associated with decreased odds of suicide (OR=0.5, p<0.01).
  30. Buralli et al.138 2020/Brazilc 42 pesticide applicators/36 farmworkers who did not apply pesticides Cross-sectional OPs Questionnaire (occupational exposure history)
Blood AChE, BChEb
Not applicable CMD (SRQ-20) Farmworkers who did not spray pesticides had a higher probability of feeling easily tired (PR=3.2; 95% CI: 1.3, 7.7) and worthless (PR=7.2; 95% CI: 1.7, 31.0) compared with pesticide applicators.
  31. Ramírez-Santana et al.134 2020/Chile 87 adults occupationally exposed (OE)/81 environmentally exposed (EE)/100 unexposed controls (RG) Cross-sectional OPs, CBs Questionnaire (occupational and residential exposure history)
Blood AChE, BChE, APEH
Not applicable Neurobehavioral performance at one (RG) or two (OE and EE) time points: general mental status (MMSE), memory (WMS III, Digit span forward, ROCF memory, 1036 A-B and A-B recall), language (WAIS subtest vocabulary), constructive praxis (ROCF copy, WAIS subtest block design), executive function (Tower of London movements and time resolution tests, WCST perseverative errors, Barcelona test categorical evocation animals and words), attention (WAIS digit span backward, d2 test, Stroop word–color and inhibitory control tests, Trail Making Test A, WAIS symbols), Psychomotricity (Purdue pegboard test, MOART reaction time, MOART finger tapping test), Mood (BDI-II depression inventory, Hamilton anxiety scale) Both exposure groups (OE and EE) had poorer executive function (Tower of London time, WCST perseverative errors), psychomotricity [MOART reaction time (right and left hand)], and mood (BDI-II depression inventory, Hamilton anxiety scale) than the RG. Seasonal exposure impaired performance in both exposure groups on all tests except those related to attention and mood. During the spray season, BChE activity was associated with decreased scores on tests of logical, auditory, and visual memory; inhibitory control of cognitive interference; constructional and planning abilities; executive function; and motor speed and coordination among those in the EE group. Weaker associations were observed for AChE levels and tests of logical memory, constructional abilities, and fine motor coordination in the EE group. In the OE group, levels of the three biomarkers were associated with worse performance on tests of inhibitory control of cognitive interference (2 tests with AChE, 2 tests with BChE, and 1 test for APEH); results were only significant for AChE.
  32. Ramírez-Santana et al.133 2020/Chile 78 adults occupationally exposed (OE)/78 environmentally exposed (EE) Cross-sectional OPs, CBs Questionnaire (occupational and residential exposure history)
Blood AChE, BChE
Not applicable Changes in neurobehavioral performance from prespray to spraying season in OE and EE: General mental status (MMSE), memory (WMS III, Digit span forward, ROCF memory, 10/36 SRT A-B and A-B recall), language (WAIS subtest vocabulary), constructive praxis (ROCF copy, WAIS subtest block design), executive function (Tower of London movements and time resolution tests, WCST perseverative errors, Barcelona test categorical evocation animals and words), attention (WAIS digit span backward, d2 test, Stroop word–color and inhibitory control tests, Trail Making Test A, WAIS symbols), Psychomotricity (Purdue pegboard test, MOART reaction time, MOART finger tapping test), Mood (BDI-II depression inventory, Hamilton anxiety scale) AChE inhibition was associated with worse performance on tests of attention (Stroop word–color and inhibitory control test, Trail Making A test) in the EE group and worse performance on tests of memory (WMS) and attention (Trail Making A test) in the OE group.
BChE inhibition was associated with worse performance on tests of general mental status (MMSE), memory (WMS III-I, WMS III-II, Digit span forward, 10/36 SRT-A, 10/36 SRT-B, 10/36 SRT-A recall, 10/36 SRT-B recall), language (WAIS), attention (Stroop word–color and inhibitory control tests), executive function (Tower of London movements, WCST perseverative errors, Barcelona tests animals) in the EE group and worse performance on a test of attention (Stroop word–color test) in the OE group.
Studies on other pesticides or multiple pesticide classes
 Studies in children
  33. Eckerman et al.143 2007/Brazil 38 adolescents (10–18 years of age) from rural areas/28 adolescents from urban areas Cross-sectional Multiple pesticide classes Questionnaire (exposure index based on 86 occupational history questions plus number of hours worked per day applying chemical plus number of years worked) Not applicable Neurobehavioral: BARS (CPT, MTS, DST, PRT, RTT, SAT, SDL, SDT, TAP) Compared with adolescents from rural areas, adolescents from urban areas performed better on tests of response speed and coordination (TAP_NP), attention and working memory (DS-F), and complex function (SD_LAT), but worse on a cognition test (SDL) (p<0.1). Among the youngest age group (10–11 y), rural participants had poorer mean scores in tests of response time and coordination (TAP_P, TAP_NP, TAP_ALT), motivation (PRT), attention and working memory (DS-F; CPT_HLAT; SAT_LAT), reaction time (RT_ALL), complex function (SDT_LAT), and visual memory and delay (MTS_LAT) (p<0.1 for each) than urban participants.
  34. Lu et al.139 2009/Costa Rica 18 children (4–10 years of age) of conventional coffee farmworkers/17 children of organic coffee farmworkers Cross-sectional OPs, herbicides, pyrethroids Child urinary 2,4-D, TCPy, 3-PBA, and IMPY Mean±SD (μg/L):
La Amistad: 2, 4-D=0.21±0.22; 3-PBA=0.75±1.61; CIT=0.27±0.41; IMPY=0.92±2.15; TCPy=0.31±0.91
Las Mellizas: 2,4-D=0.41±0.49; 3-PBA=0.4±0.22; CIT=0.14±0.26; IMPY=0.52±1.05; TCPy=1.45±2.29
Neurodevelopment: cognition (BARS, figure-drawing task, long-term memory test) Null associations between urinary pesticide metabolites and neurodevelopmental outcomes.
  35. van Wendel et al.140 2016/Costa Rica 140 rural children (6–9 years of age) living near banana and plantain plantations Cross-sectional Mn-containing fungicides, OPs, pyrethroids Questionnaire (parental occupational exposure history)
Child urinary TCPy, ETU, and 3-PBA
Median (P25–P75) (μg/L):
TCPy=1.4(0.73.1); ETU=1.2(0.73.0); 3-PBA=0.8(0.51.5)
Neurodevelopment: cognitive function (WISC-IV), behavioral problems (CPRS-R), visual sensory function (LDD-15), visuospatial construction and visual memory (ROCF), verbal memory and learning abilities (CAVLT-2), visual–motor coordination (DTVP-2), fine motor function (WRAVMA), and attention (RTT) Higher TCPy was associated with poorer working memory in boys (β per 10-fold increase in TCPy=7.5; 95% CI: 14.4, 0.7) and poorer visual–motor coordination (β=1.4; 95% CI: 2.7, 0.1); oppositional disorders (OR=6.8; 95% CI: 1.8, 28.6) and decreased ability to discriminate colors (OR=6.6; 95% CI: 1.6, 30.3) in boys and girls combined. Higher was associated with poorer verbal learning outcomes (β=7.0; 95% CI: 12.7, 1.3). Higher 3-PBA was associated with poorer processing speed scores, particularly in girls (β=8.8; 95% CI: 16.1, 1.4).
  36. Watkins et al.142 2016/Mexico 187 mother–child (2–3 years of age) pairs Prospective cohort Pyrethroids Maternal urinary 3-PBA during third trimester of pregnancy Geometric mean±GSD 3-PBA (ng/mL): 0.26 ±1.80 Neurodevelopment: cognitive, language, personal–social, fine and gross motor development (BSID-II) Children whose mothers had medium and high 3-PBA during pregnancy had lower MDI scores at 24 months than children whose mothers had low 3-PBA (β=3.5; 95% CI: 7.9, 0.8 and β=3.8; 95% CI: 8.4, 0.8, respectively). Null associations of prenatal 3-PBA with PDI scores at 24 or 36 months.
  37. Mora et al.141 2018/Costa Rica 355 mother–child (1 year of age) pairs living near banana plantations aerially sprayed Prospective cohort Mn-containing fungicides Maternal urinary ETU, blood Mn, and hair Mn during pregnancy Mean±SD (μg/L):
ETU=4.4±7.1; hair Mn(μg/g)=3.7(5.4); blood Mn=24.4±6.2
Neurodevelopment: cognition, motor function, language, and social–emotional development (BSID-III) Girls whose mothers had higher urinary ETU during pregnancy had lower social–emotional scores (β per 10-fold increase=7.4 points; 95% CI: 15.2, 0.4), whereas those whose mothers had higher hair Mn during pregnancy had lower cognitive scores (β per 10-fold increase=3.0 points; 95% CI: 6.1, 0.1). Among boys, higher hair Mn during pregnancy was associated with lower social–emotional scores (β per 10-fold increase=4.6 points; 95% CI: 8.5, 0.8). Null associations for blood Mn, language, and motor outcomes.
  38. Christian et al.145 2018/Jamaica 298 children (2–8 years of age) with ASD/298 controls without ASD Case–control Multiple pesticide classes Questionnaire (maternal exposure history) Not applicable ASD (ADOS, ADI-R) Maternal exposure to pesticides from 3 months before pregnancy to end of breastfeeding was associated with increased risk of ASD (OR=1.7; 95% CI: 1.1, 2.6), with some evidence of effect modification by exposure to oil-based paints and paint solvents.
  39. Friedman et al.144 2020/Ecuador 307 children (4–9 years of age) living in floricultural communities Cross-sectional Multiple pesticide classes Proximity to floricultural crops Not applicable Neurodevelopment: attention and inhibitory control, language, memory and learning, sensorimotor, visuospatial processing (NEPSY-II) For every 100 m closer in proximity to treated floricultural crops, participants had increased odds of low memory/learning (OR=1.2; 95% CI: 1.1, 1.5) and language (OR=1.1; 95% CI: 1.0, 1.2) scores. Compared with those living >500m from crops, those living within 50m of crops had lower language (β=1.3; 95% CI: 2.5, 0.1), attention/inhibitory control (β=1.2, 95% CI: 2.5, 0.0), and memory/learning (β=0.9; 95% CI: 2.0, 0.2) scores.
 Studies in adults
  40. Araújo et al.159 2007/Brazilc 102 farmworkers Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history)
Blood AChE
Not applicable Neurological symptoms (neurological examination and perception of neurological symptoms) Null association between inhibition of AChE activity and intoxication symptoms.
  41. Steenland et al.146 2013/Costa Rica 400 adults >60 years of age from historically (and now partially) agricultural area Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history) Not applicable Neurodegeneration: spatial and temporal orientation, short-term memory, attention, calculation, language, praxis (MMSE); PD risk (UPDRS) Exposed subjects performed worse on the MMSE than the nonexposed (p=0.01), had increased odds of abnormal scores on two UPDRS items (tremor-at-rest OR=2.3; 95% CI: 1.3–5.2 and finger tapping OR=2.9; 95% CI: 1.03, 8.4), and had an increased risk of PD (OR=2.6; 95% CI: 0.9, 7.3).
  42. Faria et al.152 2014/Brazil 2,400 tobacco farmworkers Cross-sectional Fungicides, herbicides, neonicotinoids, OPs, pyrethroids Questionnaire (occupational exposure history) Not applicable Mental health disorders: MPD (SRQ-20) Increased risk of MPD among those who entered the treated area following application (PR=1.7; 95% CI: 1.3, 2.2) and those who had contact through clothes wet from pesticides (PR=1.4; 95% CI: 1.1, 1.7). Workers from farms in which OPs were used had an increased risk of MPD compared with those who were not exposed (PR=1.5; 95% CI: 1.2, 1.9). Number of poisonings was positively associated with risk of MDP (PR for 1 episode=1.6; 95% CI: 1.1, 2.2; PR for 2 episodes=2.5; 95% CI: 1.8, 3.4).
  43. Portilla-Portilla et al.155 2014/Colombia 49 adults from a rural area Cross-sectional Multiple pesticide classes Questionnaire (occupational and environmental history of exposure to neurotoxic pesticides) Not applicable Neurological symptoms (self-reported) Participants with pesticide exposure had increased odds of irritability (PR=1.8; 95% CI: 1.1, 2.8), dizziness (PR=2.3; 95% CI: 1.1, 4.9), phosphenes (PR=2.6; 95% CI: 1.0, 6.6), epistaxis (PR=2.9; 95% CI: 1.0, 8.3), and fasciculations (PR=8.7; 95% CI: 1.1, 66.9).
  44. Campos et al.149 2016/Brazil 869 adults from a rural population Cross-sectional Herbicides, natural pesticides, OPs, OCs, pyrethroids Questionnaire (occupational exposure history) Not applicable Mental health disorders: MPD (SRQ-20) and depression (self-reported) Ever feeling ill after a pesticide application was associated with common mental disorders (OR=2.6; 95% CI: 1.6, 4.3) and self-reported depression (OR=2.6; 95% CI: 1.6, 4.2). Age at onset of pesticide exposure 15 y (OR=1.7; 95% CI: 1.7, 2.8), exposure to pyrethroids (OR=1.8; 95% CI: 1.0, 3.2) and aliphatic alcohol (OR=2.0; 95% CI: 1.04, 3.8), and greater period of exposure to dinitroaniline (OR=2.2; 95% CI: 1.0, 4.7) and sulfonyl urea (OR=5.0; 95% CI: 1.1, 23.0) were associated with self-reported depression.
  45. Azevedo and Meyer158 2017/Brazil 51 endemic disease control agents with essential tremor/204 endemic disease control agents with no tremor (controls) Case–control Larvicides, OCs, OPs, pyrethroids Questionnaire (occupational exposure history) Not applicable Neurodegeneration: essential tremor Null association of cumulative pesticide exposure load (calculated by multiplying years of application, frequency of application, and hours worked per day) with essential tremor. Workers who had applied pesticides for 16–16.9 y had increased odds of essential tremor compared with workers who had applied pesticides for 13 y (OR=4.9; 95% CI: 1.3, 18.0).
  46. Hansen et al.147 2017/Bolivia 120 male endemic disease control agents Cross-sectional Pyrethroids Questionnaire (occupational exposure history) Not applicable Neurobehavioral performance: hand tremor, postural balance, vocabulary (BNT), audiovisual reaction (RTT), cognition (BARS), visual attention (CPT), complex cognitive function (SDT), attention and memory (DST, SDL), and visual memory (MTS) Higher pesticide spraying intensity was associated with increased odds of poor postural balance among those exposed to pyrethroids (OR per 1-quintile increase in intensity=3.83; 95% CI: 1.1, 13.6). Higher spraying intensity was also associated with worse neurocognitive performance (β per 1-quintile increase for all workers=0.4; 95% CI: 0.7, 0.2 and β for workers exposed to pyrethroids only=1.3; 95% CI: 2.2, 0.5). Cumulative pesticide exposure was associated with worse neurocognitive performance (β per 1-quintile increase for all workers=0.4; 95% CI: 0.6, 0.1 and β for workers exposed to pyrethroids only=1.4; 95% CI: 2.3, 0.4).
  47. Conti et al.148 2018/Brazil 220 male farmworkers Cross-sectional Glyphosate, fungicides, neonicotinoids Questionnaire (occupational exposure history) Not applicable Mental health disorders: depression (BDI-II) Pesticide exposure was associated with increased odds of more severe depressive symptoms (OR=5.5; 95% CI: 1.2, 25.9).
  48. Palzes et al.160 2019/Costa Rica 48 farmworkers Cross-sectional Mn-containing fungicides Hair and toenail Mn Mean±SD (μg/g) Mn:
Hair=0.40±3.53; toenail=0.24±3.54
Cortical brain activity (fNIRS) Null association of hair and toenail Mn concentrations with brain activity during working memory task.
  49. Conti et al.150 2020/Brazil 288 adults from a rural area Cross-sectional Multiple pesticide classes Questionnaire (pesticide exposure in general, did not distinguish between residential and occupational) Not applicable Mental health disorders: depression (BDI-II) Pesticide use was associated with increased odds of depression (OR=4.2, p<0.001).
  50. Vasconcellos et al.156 2020/Brazil 32 participants with PD Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history) Not applicable PD 78% of patients with PD had worked in agriculture and 75% had contact with pesticides.
  51. Silvestre et al.157 2020/Brazil 88 PD cases/264 controls Case–control Multiple pesticide classes Questionnaire (occupational and environmental exposure history) Not applicable PD Pesticide use at work was associated with increased odds of PD (OR=3.4; 95% CI: 1.6, 7.6).
  52. Cruzeiro Szortyka et al.153 2021/Brazil 2,469 tobacco growers Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history, history of APP, pesticide-related work tasks) Not applicable Mental health disorders: suicidal ideation (SRQ), suicide attempts (self-reported) Performing between 6 and 9 pesticide-related tasks (PR=1.8; 95% CI: 1.0, 3.3) and history of APP (PR=2.4; 95% CI: 1.2, 4.7) were associated with increased prevalence of suicidal ideation.
  53. Gonzaga et al.154 2021/Brazil 547 farmworkers (311 occupationally exposed/236 following agroecological practices) Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history, history of APP) Not applicable Mental health disorders: suicidal ideation (SRQ-20) Occupational pesticide exposure (OR=2.3; 95% CI: 1.2, 4.6) and history of APP (OR=8.6; 95% CI: 3.0, 24.7) were associated with increased odds of suicidal ideation.
  54. Farnham et al.151 2021/Costa Rica 300 farmworkers Cross-sectional Multiple pesticide classes Questionnaire (occupational exposure history, history of APP) Not applicable Neurological symptoms
Mental health disorders: psychological distress and suicidal ideation (BSI)
Self-reported APP was associated with fainting (OR=7.5; 95% CI: 1.8, 30.7), shaking hands (OR=3.5; 95% CI: 1.6, 7.6), numbness/tingling in hands or feed (OR=3.2; 95% CI: 1.7, 6.3), insomnia (OR=2.5, 95 % CI: 1.3, 4.8), accelerated heartrate (OR=2.4; 95% CI: 1.0, 5.5), dizziness (OR=2.4; 95% CI: 1.2, 4.7), increased irritability/anger (OR=2.4; 95% CI: 1.2, 4.6), low energy (OR=2.3; 95% CI: 1.2, 4.5), and difficulty concentrating (OR=2.0; 95% CI: 1.1, 3.9) during the 12 months prior to the interview. Farmworkers who reported an APP in the 10 y prior to the interview experienced increased odds of hostility (OR=4.5; 95% CI: 1.2, 17.7) and paranoid ideation (OR=3.8; 95% CI: 1.0, 18.2).

Note: %change, percentage change; 2,4-D, 2,4-dichlorophenoxyacetate; 3-PBA, 3-phenoxybenzoic acid; AChE, acetylcholinesterase; ADHD, attention deficit hyperactivity disorder; ADI-R, Autism Diagnostic Interview–Revised; ADOS, Autism Diagnostic Observation Schedule; APEH, acyl peptide hydrolase; APP, acute pesticide poisoning; ARA, arachidonic acid; ASD, autism spectrum disorder; ASQ, Ages and Stages Questionnaire; BARS, BChE, butyrylcholinesterase; Behavioral Assessment and Research System; BASC-2, Behavior Assessment System for Children-2; BDI-II, Beck’s Depressive Inventory, 2nd edition; BNT, Boston Naming Test; BSI, Brief Symptom Inventory; BSID, Bayley Scales of Infant Development; BSID-II, Bayley Scales of Infant Development, 2nd edition; BVRT, Benton Visual Retention Test; CAVLT-2, Children’s Auditory Verbal Learning Test, 2nd edition; CB, carbamate; CDI-2, Children’s Depression inventory, 2nd edition; CI, confidence interval; CIT, 5-chloro-1,2-dihydro-1-isopropyl-[3H]-1; CMD, common mental disorders; CRS-R, Conners’ Parental Rating Scales–Revised; CPT, Continuous Performance Test; CPRS-R, Conner’s Parent Rating Scale–Revised Short Version; CPT, Continuous Performance Test; CPT_HLAT, Continuous Performance Latency for Hits; DAP, dialkylphosphate; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; DEP, diethylphosphate; DHA, docosahexaenoic acid; DMP, dimethylphosphate; DMTP, dimethylthiophosphate; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders; DS-F, DST, Digit Span Test; DTVP-2, Frostig Developmental Test of Visual Perception, 2nd edition; EE, environmentally exposed; ETU, ethylenethiourea; FAB, Frontal Assessment Battery; fNIRS, functional near-infrared spectroscopy; FrACT, functional acuity contrast test; FTII, Fagan Tests of Infant Intelligence; GSD, geometric standard deviation; HCH, hexachlorocyclohexane; IMPY, 2-isopropyl-4-methyl-6-hydroxypyrimidinol; IQ, intelligence quotient; LOD, limit of detection; LDD-15, Lanthony Desaturated D-15 Test; MASC-2, Multidimensional Anxiety Scale for Children, 2nd edition; MDI, Mental Development Index; MINI, Mini International Neuropsychiatric Interview Diagnostic Test; MMSE, Mini-Mental State Exam; Mn, manganese; MOART, multi-operational apparatus for reaction time; MPD, minor psychiatric disorders; MSCA, McCarthy Scales of Children’s Abilities; MTS, matching to sample; MTS_LAT, matching to sample latency; NESPY-II, A Developmental Neuropsychological Assessment, 2nd edition; NBAS, Brazelton Neonatal Behavioral Assessment; OC, organochlorine; OE, occupationally exposed; OP, organophosphate; OR, odds ratio; PD, Parkinson’s disease; PDI, Psychomotor Development Index; PR, probability ratio; PRT, Progressive Ratio test; RG, rural group; RGDT, Random Gap Digit test; ROCF, Rey-Osterrieth complex figure test; RT_ALL, reaction time; RTT, reaction time test; SAT, selective attention test; SAT_LAT, selective attention test latency; SD, standard deviation; SDL, serial digit learning; SDT, Symbol Digit test; SDT_LAT, Symbol Digit test latency; SRQ-20, Self-Reporting Questionnaire 20-Item; SRT, spatial recall test; TAC, total abnormal cells; TAP, tapping test; TAP_ALT, tapping with alternate hands; TAP_NP, tapping with non-preferred hand; TAP_P tapping with preferred hand; TCPy, 3,5,6-trichloro-2-pyridinol; TSH, thyroid-stimulating hormone; UPDRS, United Parkinson’s Disease Rating Motor Subscale; VMI, visual motor integration test; WAIS; Weschler Adult Intelligence Scale; WAIS-R; Weschler Adult Intelligence Scale–Revised Version; WCST, Wisconsin Card Sorting test; WISC, Weschler Intelligence Scale for Children; WMS, Wechsler Memory Scale; WRAVMA; Wide Range Assessment of Visual Motor Ability.

a

Also included in Table 6 (thyroid function).

b

Investigators did not use exposure biomarker concentrations in multivariate analyses.

c

Also included in Table 9 (other health outcomes).