Bibliography Tag: developmental impacts

Bibliography Index

Paganelli et al., 2010

Alejandra Paganelli, Victoria Gnazzo, Helena Acosta, Silvia L. López, and Andrés E. Carrasco, “Glyphosate-Based Herbicides Produce Teratogenic Effects on Vertebrates by Impairing Retinoic Acid Signaling,” Chemical Research in Toxicology, 2010, 23:10, DOI: 10.1021/TX1001749.

ABSTRACT:

The broad spectrum herbicide glyphosate is widely used in agriculture worldwide. There has been ongoing controversy regarding the possible adverse effects of glyphosate on the environment and on human health. Reports of neural defects and craniofacial malformations from regions where glyphosate-based herbicides (GBH) are used led us to undertake an embryological approach to explore the effects of low doses of glyphosate in development. Xenopus laevis embryos were incubated with 1/5000 dilutions of a commercial GBH. The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior−posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly. This suggests that glyphosate itself was responsible for the phenotypes observed, rather than a surfactant or other component of the commercial formulation. A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity. This is consistent with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal midline, with the inhibition of otx2 expression and with the disruption of cephalic neural crest development. The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.  FULL TEXT

 

Wagner-Schuman et al., 2015

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

ABSTRACT:

BACKGROUND: Pyrethroid pesticides cause abnormalities in the dopamine system and produce an ADHD phenotype in animal models, with effects accentuated in males versus females. However, data regarding behavioral effects of pyrethroid exposure in children is limited. We examined the association between pyrethroid pesticide exposure and ADHD in a nationally representative sample of US children, and tested whether this association differs by sex.

METHODS: Data are from 8-15 year old participants (N = 687) in the 2001-2002 National Health and Nutrition Examination Survey. Exposure was assessed using concurrent urinary levels of the pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). ADHD was defined by either meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria on the Diagnostic Interview Schedule for Children (DISC) or caregiver report of a prior diagnosis. ADHD symptom counts were determined via the DISC. Multivariable logistic regression examined the link between pyrethroid exposure and ADHD, and poisson regression investigated the link between exposure and ADHD symptom counts.

RESULTS: Children with urinary 3-PBA above the limit of detection (LOD) were twice as likely to have ADHD compared with those below the LOD (adjusted odds ratio [aOR] 2.42; 95 % confidence interval [CI] 1.06, 5.57). Hyperactive-impulsive symptoms increased by 50 % for every 10-fold increase in 3-PBA levels (adjusted count ratio 1.50; 95 % CI 1.03, 2.19); effects on inattention were not significant. We observed possible sex-specific effects: pyrethroid biomarkers were associated with increased odds of an ADHD diagnosis and number of ADHD symptoms for boys but not girls.

CONCLUSIONS: We found an association between increasing pyrethroid pesticide exposure and ADHD which may be stronger for hyperactive-impulsive symptoms compared to inattention and in boys compared to girls. Given the growing use of pyrethroid pesticides, these results may be of considerable public health import. FULL TEXT

Lanphear, 2015

Lanphear, Bruce, “The Impact of Toxins on the Developing Brain,” Annual Review of Public Health, 2015, 36:1, DOI: 10.1146/ANNUREV-PUBLHEALTH-031912-114413.

ABSTRACT:

The impact of toxins on the developing brain is usually subtle for an individual child, but the damage can be substantial at the population level. Numerous challenges must be addressed to definitively test the impact of toxins on brain development in children: We must quantify exposure using a biologic marker or pollutant; account for an ever-expanding set of potential confounders; identify critical windows of vulnerability; and repeatedly examine the association of biologic markers of toxins with intellectual abilities, behaviors, and brain function in distinct cohorts. Despite these challenges, numerous toxins have been implicated in the development of intellectual deficits and mental disorders in children. Yet, too little has been done to protect children from these ubiquitous but insidious toxins. The objective of this review is to provide an overview on the population impact of toxins on the developing brain and describe implications for public health.  FULL TEXT

Donauer et al., 2016

Donauer, Stephanie, Mekibib Altaye, Yingying Xu, Heidi Sucharew, Paul Succop, Antonia M. Calafat, Jane C. Khoury, Bruce Lanphear, Kimberly Yolton, “An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood,” American Journal of Epidemiology, 2016, 184:5.

ABSTRACT:

Prenatal exposure to organophosphate pesticides, which is ubiquitous, may be detrimental to neurological development. We examined 327 mother/infant pairs in Cincinnati, Ohio, between 2003 and 2006 to determine associations between prenatal exposure to organophosphate pesticides and neurodevelopment. Twice during pregnancy urinary concentrations of 6 common dialkylphosphates, nonspecific metabolites of organophosphate pesticides, were measured. Aggregate concentrations of diethylphosphates, dimethylphosphates, and total dialkylphosphates were calculated. Bayley Scales of Infant Development, Second Edition-Mental and Psychomotor Developmental indices were administered at ages 1, 2, and 3 years, the Clinical Evaluation of Language Fundamentals-Preschool, Second Edition, at age 4, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, at age 5. Mothers with higher urinary total dialkylphosphate concentrations reported higher levels of socioeconomic status and increased fresh fruit and vegetable intake. We found no associations between prenatal exposure to organophosphate pesticides and cognition at 1-5 years of age. In our cohort, exposure to organophosphate pesticides during pregnancy was not associated with cognition during early childhood. It is possible that a higher socioeconomic status and healthier diet may protect the fetus from potential adverse associations with gestational organophosphate pesticide exposure, or that dietary exposure to the metabolites is innocuous and not an ideal measure of exposure to the parent compound.

Shelton et al., 2014

Janie F. Shelton, Estella M. Geraghty, Daniel J. Tancredi, Lora D. Delwiche, Rebecca J. Schmidt, Beate Ritz, Robin L. Hansen, and Irva Hertz-Picciotto, “Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study,” Environmental Health Perspectives, 2014, 122:10, DOI: 10.1289/EHP.1307044.

ABSTRACT:

BACKGROUND: Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.

OBJECTIVES: We evaluated whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study.

METHODS: The CHARGE study is a population-based case–control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997–2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).

RESULTS: Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.

CONCLUSIONS: This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.  FULL TEXT

Glynnis English et al., 2012

René Glynnis English, Melissa Perry, Mary M. Lee, Elaine Hoffman, Steven Delport, Mohamed Aqiel Dalvie, “Farm residence and reproductive health among boys in rural South Africa,” Environment International, 2012, 47, DOI: 10.1016/J.Envint.2012.06.006.

ABSTRACT:

Few studies have investigated reproductive health effects of contemporary agricultural pesticides in boys. To determine the association between pesticide exposure and reproductive health of boys. We conducted a cross-sectional study in rural South Africa of boys living on and off farms. The study included a questionnaire (demographics, general and reproductive health, phyto-estrogen intake, residential history, pesticide exposures, exposures during pregnancy); and a physical examination that included sexual maturity development ratings; testicular volume; height, weight, body mass index; and sex hormone concentrations. Among the 269 boys recruited into the study, 177 (65.8%) were categorized as farm (high pesticide exposures) and 98 (34.2%) as non-farm residents (lower pesticide exposures). Median ages of the two groups were 11.3 vs 12.0 years, respectively (p<0.05). After controlling for confounders that included socioeconomic status, farm boys were shorter (regression coefficient (RC)=-3.42 cm; 95% confidence interval (CI): -6.38 to -0.45 cm) and weighed less (RC=-2.26 kg; CI: -4.44 to -0.75 kg). The farm boys also had lower serum lutenizing hormone (RC=-0.28 IU/L; CI: -0.48 to -0.08 IU/L), but higher serum oestradiol (RC=8.07 pmol/L; CI: 2.34-13.81 pmol/L) and follicle stimulating hormone (RC=0.63 IU/L; CI: 0.19-1.08 U/L). Our study provides evidence that farm residence is associated with adverse growth and reproductive health of pubertal boys which may be due to environmental exposures to hormonally active contemporary agricultural pesticides.

Cimino et al., 2017

Andria M. Cimino, Abee L. Boyles, Kristina A. Thayer, and Melissa J. Perry, “Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review,” Environmental Health Perspectives, 2017, 125:2, DOI: 10.1289/EHP515.

ABSTRACT:

BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species, including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure.

OBJECTIVE: In this systematic review, we sought to identify human population studies on the health effects of neonics.

METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program’s Office of Health Assessment and Translation.

RESULTS: Eight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: Three neonic poisoning studies reported two fatalities (n = 1,280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1, 5.4), anencephaly (AOR 2.9, 95% CI: 1.0, 8.2), autism spectrum disorder [AOR 1.3, 95% credible interval (CrI): 0.78, 2.2], and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5, 57). Reported odds ratios were based on exposed compared to unexposed groups.

CONCLUSIONS: The studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more studies are needed to fully understand their effects on human health.  FULL TEXT

Herzine et al., 2016

Ameziane Herzine, Anthony Laugeray, Justyne Feat, Arnaud Menuet, Valérie Quesniaux, Olivier Richard, Jacques Pichon, Céline Montécot-Dubourg, Olivier Perche, and Stéphane Mortaud,”Perinatal Exposure to Glufosinate Ammonium Herbicide Impairs Neurogenesis and Neuroblast Migration through Cytoskeleton Destabilization,” Frontiers in Cellular Neuroscience, 2016, 10:191, DOI: 10.3389/FNCEL.2016.00191.

ABSTRACT:

Neurogenesis, a process of generating functional neurons from neural precursors, occurs throughout life in restricted brain regions such as the subventricular zone (SVZ). During this process, newly generated neurons migrate along the rostral migratory stream to the olfactory bulb to replace granule cells and periglomerular neurons. This neuronal migration is pivotal not only for neuronal plasticity but also for adapted olfactory based behaviors. Perturbation of this highly controlled system by exogenous chemicals has been associated with neurodevelopmental disorders. We reported recently that perinatal exposure to low dose herbicide glufosinate ammonium (GLA), leads to long lasting behavioral defects reminiscent of Autism Spectrum Disorder-like phenotype in the offspring (Laugeray et al., 2014). Herein, we demonstrate that perinatal exposure to low dose GLA induces alterations in neuroblast proliferation within the SVZ and abnormal migration from the SVZ to the olfactory bulbs. These disturbances are not only concomitant to changes in cell morphology, proliferation and apoptosis, but are also associated with transcriptomic changes. Therefore, we demonstrate for the first time that perinatal exposure to low dose GLA alters SVZ neurogenesis. Jointly with our previous work, the present results provide new evidence on the link between molecular and cellular consequences of early life exposure to the herbicide GLA and the onset of ASD-like phenotype later in life.  FULL TEXT

Skinner et al., 2013a

Skinner MK, Guerrero-Bosagna C, Haque M, Nilsson E, Bhandari R, McCarrey JR, “Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line,” PLoS One, 2013, 8:7, DOI: 10.1371/journal.pone.0066318.  (Erratum in PLoS One. 2013;8(7). DOI:10.1371/annotation/7683bb48-85db-4c7e-87c0-304a7d53a587.)

ABSTRACT: A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.   FULL TEXT

Winchester et al., 2017

Winchester PD, Parvez S, Proctor C, Ying J, Gerona RR, “Fetal Exposure to Glyphosate,” Presentation, Pediatric Academic Societies, May 6-7, 2017, San Francisco, California.

SUMMARY:

Measured glyphosate in pregnant women to estimate fetal exposure and monitor potential adverse effects on pregnancy outcomes. Glyphosate was present in 91% of the urine samples and higher glyphosate levels were correlated with shorter pregnancies and lower birth weights.  FULL TEXT

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