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.
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
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.
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.
Manservisi, Fabiana, Lesseur, Corina, Panzacchi, Simona, Mandrioli, Daniele, Falcioni, Laura, Bua, Luciano, Manservigi, Marco, Spinaci, Marcella, Galeati, Giovanna, Mantovani, Alberto, Lorenzetti, Stefano, Miglio, Rossella, Andrade, Anderson Martino, Kristensen, David Møbjerg, Perry, Melissa J., Swan, Shanna H., Chen, Jia, & Belpoggi, Fiorella. “The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system,” Environmental Health, 2019, 18(1). DOI:10.1186/s12940-019-0453-y.
BACKGROUND: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be “safe” (the US Acceptable Daily Intake – ADI – of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats.
METHODS: Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups.
RESULTS: In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure.
CONCLUSIONS: The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female. FULL TEXT
Panzacchi, S., Mandrioli, D., Manservisi, F., Bua, L., Falcioni, L., Spinaci, M., Galeati, G., Dinelli, G., Miglio, R., Mantovani, A., Lorenzetti, S., Hu, J., Chen, J., Perry, M. J., Landrigan, P. J., & Belpoggi, F. “The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation,” Environmental Health, 17(1), 52, 2018. doi:10.1186/s12940-018-0393-y.
BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.
METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.
RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.
CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model. FULL TEXT
Melissa J. Perry, Anne Marbella, Peter M. Layde, “Nonpersistent Pesticide Exposure Self-report versus Biomonitoring in Farm Pesticide Applicators,” Annals of Epidemiology, 2006, 16:9, DOI: 10.1016/J.ANNEPIDEM.2005.12.004.
PURPOSE: Few studies using biologic markers to examine nonpersistent pesticide exposure among pesticide applicators were conducted in field settings. This study compares self-reported dermal, inhalation, and ingestion exposures with urinalysis results after one-time application of the commonly used herbicide atrazine to field crops. It was hypothesized that: i) applicator reports of exposure would be associated positively with detection of urinary atrazine metabolites, and ii) applicator reports of personal-protective-equipment (PPE) use would be associated negatively with detection of urinary atrazine metabolites.
METHODS: Wisconsin dairy farmers were randomly selected to participate in 1997 to 1998 and were instructed to collect a urine sample 8 hours after the first pesticide application of the season. Farmers then were interviewed within 1 week of their first application to report on application practices. Eighty-six urine samples were analyzed for deethylatrazine, a major atrazine metabolite.
RESULTS: Comparing urinalysis results with self-reported dermal, inhalation, and ingestion exposure showed poor agreement between self-reported exposure and urinary deethylatrazine detections (all κ < 0.40). Multivariate linear regression modeling with deethylatrazine level as the outcome showed that self-reported practices did not significantly predict atrazine metabolite levels.
CONCLUSIONS: Possible explanations for the discrepancies between urinalysis results and self-reported data include: i) inaccuracies in self-reported data and ii) substantial interpersonal variation in atrazine metabolism, resulting in major differences in body burden for similar exposures. Either explanation poses challenges for epidemiologic studies of the health effects of pesticides, which rely solely on self-reported measures of exposure. Additional evaluation of determinants of accuracy in self-assessed occupational and environmental exposures is needed.
Perry MJ, Venners SA, Barr DB, Xu X., “Environmental pyrethroid and organophosphorus insecticide exposures and sperm concentration,” Reproductive Toxicology, 2007, 23:1, DOI: 10.1016/J.REPROTOX.2006.08.005.
BACKGROUND: There is growing concern that poisoning and other adverse health effects are increasing because organophosphorous (OP) insecticides are now being used in combination with pyrethroid (PYR) insecticides to enhance the toxic effects of PYR insecticides on target insects, especially those that have developed PYR resistance.
OBJECTIVES: We conducted a pilot biomonitoring study to determine whether men in our reproductive cohort study were being exposed to pesticides environmentally by virtue of frequenting an agricultural setting.
METHODS: We screened 18 randomly selected urine samples collected from male participants of reproductive age for 24 parent compounds and metabolites of pesticides and examined the results in relation to sperm concentration.
RESULTS: Results showed high prevalence of exposure to OP and PYR pesticides and our preliminary analyses provided some suggestion that the higher exposure group had lower sperm concentration.
CONCLUSIONS: The potential of OP/PYR mixtures to have enhanced human toxicity needs more research attention.
Melissa J. Perry, Scott A. Venners, Xing Chen, Xue Liu, Genfu Tang, Houxun Xing, Dana Boyd Barr, Xiping Xu, “Organophosphorous pesticide exposures and sperm quality,” Reproductive Toxicology, 2011, 31:1, DOI: 10.1016/j.reprotox.2010.08.006.
Many Americans are exposed to low levels of organophosphorous (OP) pesticides. It is unclear whether these exposures impact sperm production. We investigated whether there was an association between urinary OP insecticide metabolites and sperm concentration and motility in newly married men from a rural area of eastern People’s Republic of China. Ninety-four cases and 95 controls were included based on their median residual value of sperm concentration and motility after adjusting for relevant covariates. Their urine was analyzed for six dialkylphosphate (DAP) compounds. After adjustment for demographic and exposure variables, the odds of being a case were greater (odds ratio = 1.30, 95% confidence interval 1.02–1.65) in men with higher urinary concentrations of dimethylphosphate (DMP) compared to men with lower levels. No significant differences between cases and controls were found among the other DAP concentrations. DMP exposure and sperm concentration and motility should be explored further in environmental exposure studies.
Melissa J. Perry, “Effects of environmental and occupational pesticide exposure on human sperm: a systematic review,” Human Reproduction Update, 2008, 14:3, DOI: 10.1093/HUMUPD/DMM039.
Relatively recent discoveries of the hormone disrupting properties of some pesticides have raised interest in how contemporary pesticide exposures, which primarily take the form of low level environmental or occupational exposures, impact spermatogenesis. The objective of the present review was to summarize results to date of studies examining pesticide effects on human sperm. Outcomes evaluated included sperm parameters, DNA damage and numerical chromosome aberrations (aneuploidy (disomy, nullisomy) or diploidy). Studies investigating sperm in men environmentally and/or occupationally exposed to any types of pesticides were included in the review. The targeted literature search over the last 15 years showed a range of pesticide classes have been investigated including pyrethroids, organophosphates, phenoxyacetic acids, carbamates, organochlorines and pesticide mixtures. None of the studies involved acute exposure events such as chemical accidents. There were 20 studies evaluating semen quality, of which 13 studies reported an association between exposure and semen quality; 6 studies evaluating DNA damage, of which 3 reported an association with exposure; and 6 studies assessing sperm aneuploidy or diploidy, of which 4 reported an association with exposure. Studies varied widely in methods, exposures and outcomes. Although suggestive for semen parameters, the epidemiologic evidence accumulated thus far remains equivocal as to the spermatotoxic and aneugenic potential of pesticides given the small number of published studies. This question warrants more investigation and suggestions for future studies are outlined. FULL TEXT
Christopher J Portier, Bruce K Armstrong, Bruce C Baguley, Xaver Baur, Igor Belyaev, Robert Bellé, Fiorella Belpoggi, Annibale Biggeri, Maarten C Bosland, Paolo Bruzzi, Lygia Therese Budnik, Merete D Bugge, Kathleen Burns, Gloria M Calaf, David O Carpenter, Hillary M Carpenter, Lizbeth López-Carrillo, Richard Clapp, Pierluigi Cocco, Dario Consonni, Pietro Comba, Elena Craft, Mohamed Aqiel Dalvie, Devra Davis, Paul A Demers, Anneclaire J De Roos, Jamie DeWitt, Francesco Forastiere, Jonathan H Freedman, Lin Fritschi, Caroline Gaus, Julia M Gohlke, Marcel Goldberg, Eberhard Greiser, Johnni Hansen, Lennart Hardell, Michael Hauptmann, Wei Huang, James Huff, Margaret O James, C W Jameson, Andreas Kortenkamp, Annette Kopp-Schneider, Hans Kromhout, Marcelo L Larramendy, Philip J Landrigan, Lawrence H Lash, Dariusz Leszczynski, Charles F Lynch, Corrado Magnani, Daniele Mandrioli, Francis L Martin, Enzo Merler, Paola Michelozzi, Lucia Miligi, Anthony B Miller, Dario Mirabelli, Franklin E Mirer, Saloshni Naidoo, Melissa J Perry, Maria Grazia Petronio, Roberta Pirastu, Ralph J Portier, Kenneth S Ramos, Larry W Robertson, Theresa Rodriguez, Martin Röösli, Matt K Ross, Deodutta Roy, Ivan Rusyn, Paulo Saldiva, Jennifer Sass, Kai Savolainen, Paul T J Scheepers, Consolato Sergi, Ellen K Silbergeld, Martyn T Smith, Bernard W Stewart, Patrice Sutton, Fabio Tateo, Benedetto Terracini, Heinz W Thielmann, David B Thomas, Harri Vainio, John E Vena, Paolo Vineis, Elisabete Weiderpass, Dennis D Weisenburger, Tracey J Woodruff, Takashi Yorifuji, Il Je Yu, Paola Zambon, Hajo Zeeb,Shu-Feng Zhou, “Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA),” Journal of Epidemiology and Community Health, 2016, 0:0, DOI: 10.1136/JECH-2015-207005.
Nathan Raines MPH, Marvin González MD MS, Christina Wyatt MD MS, Mark Kurzrok, Christopher Pool, Tiziana Lemma, Ilana Weiss MPH, Carlos Marín, Valerio Prado, Eugenia Marcas, Karina Mayorga, Jean Franco Morales, Aurora Aragón MD PhD, Perry Sheffield MD MPH, “Risk Factors for Reduced Glomerular Filtration Rate in a Nicaraguan Community Affected by Mesoamerican Nephropathy,” MEDICC Review, 2014, 16:2.
INTRODUCTION: Mesoamerican nephropathy, also known as chronic kidney disease of unknown etiology, is widespread in Pacific coastal Central America. The cause of the epidemic is unknown, but the disease may be linked to multiple factors, including diet as well as environmental and occupational exposures. As many as 50% of men in some communities have Mesoamerican nephropathy.
OBJECTIVE: Describe prevalence of reduced glomerular filtration rate in a region of Nicaragua suspected to harbor high rates of Mesoamerican nephropathy; and investigate potential risk factors for such reduction associated with agricultural work (such as pesticide exposure and specific agricultural tasks associated with increased heat stress); sugar consumption; and traditional factors such as age, sex, diabetes, hypertension and nephrotoxic medication use.
METHODS: This study uses a cross-sectional design with nested case-control analysis. Cases were individuals with estimated glomerular filtration rates of <60 mL/min/1.73 m2 and controls were individuals with those >90mL/min/1.73 m2 , estimated using serum creatinine. Data on nutrition, past medical history, medication and substance use, and agricultural behaviors and exposures were collected using medical questionnaires from June through August, 2012. Venous blood and urine samples were collected to assess hemoglobin A1c, and dipstick proteinuria, respectively; anthropometry and blood pressure measurements were made using standard techniques. Analyses were conducted using chi square, and univariate and multiple logistic regression.
RESULTS: Of 424 individuals in the study, 151 had an occupational history in agriculture. Prevalence of glomerular filtration rate <60 mL/ min/1.73 m2 was 9.8% among women and 41.9% among men (male to female ratio = 4.3, p<0.0001). Proteinuria > or equal to 300 mg/dL was observed in <10% of participants with decreased glomerular filtration rate. Hemoglobin A1c and use of NSAIDs were not associated with decreased glomerular filtration rate. Although systolic and diastolic blood pressure was higher among participants with decreased glomerular filtration rate (p <0.001), hypertension was uncommon. Significant agricultural risk factors for reduced glomerular filtration rate included increased lifetime days cutting sugarcane during the dry season (OR 5.86, 95% CI 2.45–14.01), nondeliberate pesticide inhalation (OR 3.31, 95% CI 1.32–8.31), and sugarcane chewing (OR 3.24, 95% CI 1.39–7.58).
CONCLUSIONS: Our findings demonstrate a high prevalence of chronic kidney disease not linked to traditional risk factors, and suggest it may be associated instead with occupational exposure to heat stress in conjunction with pesticide inhalation, sugarcane chewing and sugar intake during the workday. FULL TEXT