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Séralini et al., 2014

Gilles-Eric Séralini, Emilie Clair, Robin Mesnage, Steeve Gress, Nicolas Defarge, Manuela Malatesta, Didier Hennequin and Joël Spiroux de Vendômois, “Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize,” Environmental Sciences Europe, Bridging Science and Regulation at the Regional and European Level, 2014, 26:14. DOI: 10.1186/s12302-014-0014-5

ABSTRACT

BACKGROUND: The health effects of a Roundup-tolerant NK603 genetically modified (GM) maize(from 11% in the diet), cultivated with or without Roundup application and Roundup alone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) in drinking water, were evaluated for 2 years in rats. This study constitutes a follow-up investigation of a 90-day feeding study conducted by Monsanto in order to obtain commercial release of this GMO, employing the same rat strain and analyzing biochemical parameters on the same number of animals per group as our investigation. Our research represents the first chronic study on these substances, in which all observations including tumors are reported chronologically. Thus, it was not designed as a carcinogenicity study. We report the major findings with 34 organs observed and 56 parameters analyzed at 11 time points for most organs.

RESULTS: Biochemical analyses confirmed very significant chronic kidney deficiencies, for all treatments and both sexes; 76% of the altered parameters were kidney-related.In treated males, liver congestions and necrosis were 2.5 to 5.5 times higher.Marked and severe nephropathies were also generally 1.3 to 2.3 times greater. In females, all treatment groups showed a two- to threefold increase in mortality,and deaths were earlier. This difference was also evident in three male groups fed with GM maize. All results were hormone- and sex-dependent, and the pathological profiles were comparable. Females developed large mammary tumors more frequently and before controls; the pituitary was the second most disabled organ; the sex hormonal balance was modified by consumption of GM maize and Roundup treatments.Males presented up to four times more large palpable tumors starting 600 days earlier than in the control group, in which only one tumor was noted. These results may be explained by not only the non-linear endocrine-disrupting effects of Roundup but also by the over expression of the EPSPS transgene or other mutational effects in the GM maize and their metabolic consequences.

CONCLUSION: Our findings imply that long-term (2 year) feeding trials need to be conducted to thoroughly evaluate the safety of GM foods and pesticides in their full commercial formulations. FULL TEXT

Eriksson et al., 2008

Mikael Eriksson, Lennart Hardell, Michael Carlberg and Måns Åkerman, “Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis,” International Journal of Cancer, 2008, 123, DOI: 10.1002/ijc.23589

ABSTRACT:

We report a population based case–control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18–74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to different agents was assessed by questionnaire. In total 910 (91%) cases and 1016(92%) controls participated. Exposure to herbicides gave odds ratio(OR) 1.72, 95% conﬁdence interval (CI) 1.18–2.51. Regarding phenoxyacetic acids highest risk was calculated for MCPA; OR 2.81,95% CI 1.27–6.22, all these cases had a latency period >10 years.Exposure to glyphosate gave OR 2.02, 95% CI 1.10–3.71 and with>10 years latency period OR 2.26, 95% CI 1.16–4.40. Insecticides overall gave OR 1.28, 95% CI 0.96–1.72 and impregnating agents OR 1.57, 95% CI 1.07–2.30. Results are also presented for different entities of NHL. In conclusion our study conﬁrmed an association between exposure to phenoxyacetic acids and NHL and the association with glyphosate was considerably strengthened. FULL TEXT

Bellinger, 2012

David C. Bellinger, “A Strategy for Comparing the Contributions of Environmental Chemicals and Other Risk Factors to Neurodevelopment of Children,” Environmental Health Perspectives, 2012, 120:4, DOI: 10.1289/ehp.1104170

ABSTRACT:

BACKGROUND: The impact of environmental chemicals on children’s neurodevelopment is sometimes dismissed as unimportant because the magnitude of the impairments are considered to be clinically insignificant. Such a judgment reflects a failure to distinguish between individual and population risk. The population impact of a risk factor depends on both its effect size and its distribution (or incidence/prevalence).

OBJECTIVE: The objective was to develop a strategy for taking into account the distribution (or incidence/prevalence) of a risk factor, as well as its effect size, in order to estimate its population impact on neurodevelopment of children.

METHODS: The total numbers of Full-Scale IQ points lost among U.S. children 0–5 years of age were estimated for chemicals (methylmercury, organophosphate pesticides, lead) and a variety of medical conditions and events (e.g., preterm birth, traumatic brain injury, brain tumors, congenital
heart disease).

DISCUSSION: Although the data required for the analysis were available for only three environmental chemicals (methylmercury, organophosphate pesticides, lead), the results suggest that their contributions to neurodevelopmental morbidity are substantial, exceeding those of many nonchemical risk factors.

CONCLUSION: A method for comparing the relative contributions of different risk factors provides a rational basis for establishing priorities for reducing neurodevelopmental morbidity in children. FULL TEXT

De Roos et al., 2003

A J De Roos, S Zahm, K Cantor, D Weisenburger, F Holmes, L Burmeister, and A Blair, “Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men,” Occupational and Environmental Medicine, 2003, 60:9, DOI: 10.1136/oem.60.9.e1

ABSTRACT:

METHODS: During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.

RESULTS: Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these “potentially carcinogenic” pesticides suggested a positive trend of risk with exposure to increasing numbers.

CONCLUSION: Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios. FULL TEXT

Cabello et al., 2001

Gertrudis Cabello, Mario Valenzuela, Arnaldo Vilaxa, Viviana Durán, Isolde Rudolph, Nicolas Hrepic, and Gloria Calaf, “A Rat Mammary Tumor Model Induced by the Organophosphorous Pesticides Parathion and Malathion, Possibly through Acetylcholinesterase Inhibition,” Environmental Health Perspectives, 2001, 109:5.

ABSTRACT:

Environmental chemicals may be involved in the etiology of breast cancers. Many studies have addressed the association between cancer in humans and agricultural pesticide exposure. Organophosphorous pesticides have been used extensively to control mosquito plagues. Parathion and malathion are organophosphorous pesticides extensively used to control a wide range of sucking and chewing pests of field crops, fruits, and vegetables. They have many structural similarities with naturally occurring compounds, and their primary target of action in insects is the nervous system; they inhibit the release of the enzyme acetylcholinesterase at the synaptic junction. Eserine, parathion, and malathion are cholinesterase inhibitors responsible for the hydrolysis of body choline esters, including acetylcholine at cholinergic synapses. Atropine, a parasympatholytic alkaloid, is used as an antidote to acetylcholinesterase inhibitors. The aim of this study was to examine whether pesticides were able to induce malignant transformation of the rat mammary gland and to determine whether alterations induced by these substances increase the cholinergic activation influencing such transformation. These results showed that eserine, parathion, and malathion increased cell proliferation of terminal end buds of the 44-day-old mammary gland of rats, followed by formation of 8.6, 14.3, and 24.3% of mammary carcinomas, respectively, after about 28 months. At the same time, acetylcholinesterase activity decreased in the serum of these animals from 9.78 +/- 0.78 U/mL in the control animals to 3.05 +/- 0.06 U/mL; 2.57 +/- 0.15 U/mL; and 3.88 +/- 0.44 U/mL in the eserine-, parathion-, and malathion-treated groups, respectively. However, atropine alone induced a significant (p < 0.05) decrease in the acetylcholinesterase activity from the control value of 9.78 +/- 0.78 to 4.38 +/- 0.10 for atropine alone, to 1.32 +/- 0.06 for atropine in combination with eserine, and 2.39 +/- 0.29 for atropine with malathion, and there was no mammary tumor formation. These results indicate that organophosphorous pesticides induce changes in the epithelium of mammary gland influencing the process of carcinogenesis, and such alterations occur at the level of nervous system by increasing the cholinergic stimulation. FULL TEXT

Loomis et al., 2015

Dana Loomis, Kathryn Guyton, Yann Grosse, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Heidi Mattock, Kurt Straif, “Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid,” The Lancet, 2015, 16, DOI: 10.1016/S1470-2045(15)00081-9.

SUMMARY:

Summarizes the findings of 26 experts from 13 countries who met at the International Agency for Research on Cancer (IARC; Lyon, France) to assess the carcinogenicity of the insecticides lindane and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) for IARC Monographs Volume 113. 2,4-D was classified as “possibly carcinogenic to humans” (Group 2B) after some studies showed links to cancers including non-Hodgkin’s lymphoma. FULL TEXT

Bouchard et al., 2011

Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr DB, Eskenazi B., “Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children.,” Environmental Health Perspectives, 2011, 119:8, DOI: 10.1289/ehp.1003185.

ABSTRACT:
CONTEXT: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development.

OBJECTIVE: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.

METHODS: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.

RESULTS: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.

CONCLUSIONS: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population. FULL TEXT

Schütte et al., 2017

Gesine Schütte, Michael Eckerstorfer, Valentina Rastelli, Wolfram Reichenbecher, Sara Restrepo‑Vassalli, Marja Ruohonen‑Lehto, Anne‑Gabrielle Wuest Saucy, and Martha Mertens, “Herbicide resistance and biodiversity: agronomic and environmental aspects of genetically modified herbicide-resistant plants,” Environmental Sciences Europe, 2017, 29:5, DOI: 10.1186/s12302-016-0100-y.

ABSTRACT:

Farmland biodiversity is an important characteristic when assessing sustainability of agricultural practices and is of major international concern. Scientific data indicate that agricultural intensification and pesticide use are among the main drivers of biodiversity loss. The analysed data and experiences do not support statements that herbicide-resistant crops provide consistently better yields than conventional crops or reduce herbicide amounts. They rather show that the adoption of herbicide-resistant crops impacts agronomy, agricultural practice, and weed management and contributes to biodiversity loss in several ways: (i) many studies show that glyphosate-based herbicides, which were commonly regarded as less harmful, are toxic to a range of aquatic organisms and adversely affect the soil and intestinal microflora and plant disease resistance; the increased use of 2,4-D or dicamba, linked to new herbicide-resistant crops, causes special concerns. (ii) The adoption of herbicide-resistant crops has reduced crop rotation and favoured weed management that is solely based on the use of herbicides. (iii) Continuous herbicide resistance cropping and the intensive use of glyphosate over the last 20 years have led to the appearance of at least 34 glyphosate-resistant weed species worldwide. Although recommended for many years, farmers did not counter resistance development in weeds by integrated weed management, but continued to rely on herbicides as sole measure. Despite occurrence of widespread resistance in weeds to other herbicides, industry rather develops transgenic crops with additional herbicide resistance genes. (iv) Agricultural management based on broad-spectrum herbicides as in herbicide-resistant crops further decreases diversity and abundance of wild plants and impacts arthropod fauna and other farmland animals. Taken together, adverse impacts of herbicide-resistant crops on biodiversity, when widely adopted, should be expected and are indeed very hard to avoid. For that reason, and in order to comply with international agreements to protect and enhance biodiversity, agriculture needs to focus on practices that are more environmentally friendly, including an overall reduction in pesticide use. (Pesticides are used for agricultural as well non-agricultural purposes. Most commonly they are used as plant protection products and regarded as a synonym for it and so also in this text.) FULL TEXT

Eskenazi et al., 2004

Brenda Eskenazi, Kim Harley, Asa Bradman, Erin Weltzien, Nicholas P. Jewell, Dana B. Barr, Clement E. Furlong, and Nina T. Holland, “Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Length of Gestation in an Agricultural Population,” Environmental Health Perspecitives, 112:10, 2004, DOI: 10.1289/ehp.6789

ABSTRACT:

Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures.
However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = –0.41 weeks per log10 unit increase; 95% confidence interval (CI), –0.75––0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13–0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population. FULL TEXT

Ranjbar et al., 2015

Mahsa Ranjbar, Michael A. Rotondi, Chris I. Ardern, and Jennifer L. Kuk, “The Influence of Urinary Concentrations of Organophosphate Metabolites on the Relationship between BMI and Cardiometabolic Health Risk,” Journal of Obesity, 2015, DOI: 10.1155/2015/687914

ABSTRACT:

The objective was to determine whether detectable levels of OP metabolites influence the relationship between BMI and cardiometabolic health. This cross-sectional study was conducted using 2227 adults from the 1999–2008 NHANES datasets. Urinary concentrations of six dialkyl phosphate metabolites were dichotomized to above and below the detection limit. Weighted multiple regression analysis was performed adjusting for confounding variables. Independent of BMI, individuals with detectable metabolites had higher diastolic blood pressure (for dimethylphosphate, diethylphosphate, and diethyldithiophosphate; ???? < 0.05), lower HDL (for diethyldithiophosphate; ???? = 0.02), and higher triglyceride (for dimethyldithiophosphate; ???? = 0.05) than those below detection. Contrarily, those with detectable dimethylthiophosphate had better LDL, HDL, and total cholesterol, independent of BMI. Individuals at a higher BMI range who had detectable diethylphosphate (interaction: ???? = 0.03) and diethylthiophosphate (interaction: ???? = 0.02) exhibited lower HDL, while little difference existed between OP metabolite detection statuses at lower BMIs. Similarly, individuals with high BMIs and detectable diethylphosphate had higher triglyceride than those without detectable levels, while minimal differences between diethylphosphate detection statuses were observed at lower BMIs (interaction: ???? = 0.02). Thus, cardiometabolic health outcome differs depending on the specific OP metabolite being examined, with higher BMIs amplifying health risk. FULL TEXT

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