Other Health Risks

Brändli et al., 2012

Dirk Brändli and Sandra Reinacher, “Herbicides found in Human Urine,” Ithaka Journal, 1/2012, 2012


Glyphosate is the main active substance used in most commercial herbicides. It poisons not only plants, but also animals and humans. When testing for glyphosate contamination in an urban population, a German university found significant contamination in all urine samples with levels 5 to 20 times above the legal limit for drinking water.  Glyphosate background info, health risks, and reasons for contamination are discussed.  FULL TEXT

Islam et al., 2018

Faisal Islam, Jian Wang, Muhammad A. Farooq, Muhammad S.S. Khan, Ling Xu, Jinwen Zhu, Min Zhao, Stéphane Muños, Qing X. Li, Weijun Zhou, “Potential impact of the herbicide 2,4-dichlorophenoxyacetic acid on human and ecosystems,” Environment International, 2018, 111, DOI: 10.1016/j.envint.2017.10.020.

ABSRACT: The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is applied directly to aquatic and conventional farming systems to control weeds, and is among the most widely distributed pollutants in the environment. Non-target organisms are exposed to 2,4-D via several ways, which could produce toxic effects depending on the dose, frequency of exposure, and the host factors that influence susceptibility and sensitivity. An increasing number of experimental evidences have shown concerns about its presence/detection in the environment, because several investigations have pointed out its potential lethal effects on non-target organisms. In this review, we critically evaluated the environmental fate and behavior of 2,4-D along with its eco-toxicological effects on aquatic, plants and human life to provide concise assessment in the light of recently published reports. The findings demonstrate that 2,4-D is present in a low concentration in surface water of regions where its usage is high. The highest concentrations of 2,4-D were detected in soil, air and surface water surrounded by crop fields, which suggest that mitigation strategies must be implanted locally to prevent the entry of 2,4-D into the environment. A general public may have frequent exposure to 2,4-D due to its wide applications at home lawns and public parks, etc. Various in vivo and in vitro investigations suggest that several species (or their organs) at different trophic levels are extremely sensitive to the 2,4-D exposure, which may explain variation in outcomes of reported investigations. However, implications for the prenatal exposure to 2,4-D remain unknown because 2,4-D-induced toxicity thresholds in organism have only been derived from juveniles or adults. In near future, introduction of 2,4-D resistant crops will increase its use in agriculture, which may cause relatively high and potentially unsafe residue levels in the environment. The recent findings indicate the urgent need to further explore fate, accumulation and its continuous low level exposure impacts on the environment to generate reliable database which is key in drafting new regulation and policies to protect the population from further exposure.

Jayasumana et al., 2014

Channa Jayasumana, Sarath Gunatilake, and Priyantha Senanayake, “Glyphosate, Hard Water and Nephrotoxic Metals: Are They the Culprits Behind the Epidemic of Chronic Kidney Disease of Unknown Etiology in Sri Lanka?,” International Journal of Environmental Research and Public Health, 2014,  11, DOI:10.3390/IJERPH 110202125.


The current chronic kidney disease epidemic, the major health issue in the rice paddy farming areas in Sri Lanka has been the subject of many scientific and political debates over the last decade. Although there is no agreement among scientists about the etiology of the disease, a majority of them has concluded that this is a toxic nephropathy. None of the hypotheses put forward so far could explain coherently the totality of clinical, biochemical, histopathological findings, and the unique geographical distribution of the disease and its appearance in the mid-1990s. A strong association between the consumption of hard water and the occurrence of this special kidney disease has been observed, but the relationship has not been explained consistently. Here, we have hypothesized the association of using glyphosate, the most widely used herbicide in the disease endemic area and its unique metal chelating properties. The possible role played by glyphosate-metal complexes in this epidemic has not been given any serious consideration by investigators for the last two decades. Furthermore, it may explain similar kidney disease epidemics observed in Andra Pradesh (India) and Central America. Although glyphosate alone does not cause an epidemic of chronic kidney disease, it seems to have acquired the ability to destroy the renal tissues of thousands of farmers when it forms complexes with a localized geo environmental factor (hardness) and nephrotoxic metals.   FULL TEXT

Jayasumana et al., 2015

Channa Jayasumana, Sarath Gunatilake, and Sisira Siribaddana, “Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy,” BMC Nephrology, 2015, 16:103, DOI 10.1186/s12882-015-0109-2.


BACKGROUND: Sri Lankan Agricultural Nephropathy (SAN), a new form of chronic kidney disease among paddy farmers was first reported in 1994. It has now become the most debilitating public health issue in the dry zone of Sri Lanka. Previous studies showed SAN is a tubulo-interstitial type nephropathy and exposure to arsenic and cadmium may play a role in pathogenesis of the disease.

METHODS: Urine samples of patients with SAN (N = 10) from Padavi-Sripura, a disease endemic area, and from two sets of controls, one from healthy participants (N = 10) from the same endemic area and the other from a non-endemic area (N = 10; Colombo district) were analyzed for 19 heavy metals and for the presence of the pesticide- glyphosate.

RESULTS: In both cases and the controls who live in the endemic region, median concentrations of urinary Sb, As, Cd, Co, Pb, Mn, Ni, Ti and V exceed the reference range. With the exception of Mo in patients and Al, Cu, Mo, Se, Ti and Zn in endemic controls, creatinine adjusted values of urinary heavy metals and glyphosate were significantly higher when compared to non-endemic controls. Creatinine unadjusted values were significant higher for 14 of the 20 chemicals studied in endemic controls and 7 in patients, compared to non-endemic controls. The highest urinary glyphosate concentration was recorded in SAN patients (range 61.0-195.1 μg/g creatinine).

CONCLUSTIONS: People in disease endemic area exposed to multiple heavy metals and glyphosate. Results are supportive of toxicological origin of SAN that is confined to specific geographical areas. Although we could not localize a single nephrotoxin as the culprit for SAN, multiple heavy metals and glyphosates may play a role in the pathogenesis. Heavy metals excessively present in the urine samples of patients with SAN are capable of causing damage to kidneys. Synergistic effects of multiple heavy metals and agrochemicals may be nephrotoxic.  FULL TEXT

Koureas et al., 2011

Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C., “Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes,” Toxicology Letters,  2012, 210:2, DOI: 10.1016/j.toxlet.2011.10.007.


For the appropriate protection of human health it is necessary to accurately estimate the health effects of human exposure to toxic compounds. In the present  review, epidemiological studies on the health effects of human exposure to organophosphorus  (OP) and pyrethroid (PYR) insecticides have been critically assessed. This review is focused on studies where the exposure assessment was based on quantification of specific biomarkers in urine or plasma. The 49 studies reviewed used different epidemiological approaches and analytical methods as well as different exposure assessment methodologies. With regard to OP pesticides, the studies reviewed suggested negative effects of prenatal exposure to these pesticides on neurodevelopment and male reproduction. Neurologic effects on adults, DNA damage and adverse birth outcomes were also associated with exposure to OP pesticides. With regard to exposure to PYR pesticides, there are currently few studies investigating the adverse health outcomes due to these pesticides. The effects studied in relation to PYR exposure were mainly male reproductive effects (sperm quality, sperm DNA damage and reproductive hormone disorders). Studies’ findings provided evidence to support the hypothesis that PYR exposure is adversely associated with effects on the male reproductive system. The validity of these epidemiological studies is strongly enhanced by exposure assessment based on biomarker quantification. However, for valid and reliable results and conclusions, attention should also be focused on the validity of the analytical methods used, study designs and the measured toxicants characteristics.

Landrigan and Belpoggi, 2018

Landrigan, P. J., and Belpoggi, F.,”The need for independent research on the health effects of glyphosate-based herbicides,” Environmental Health, 17(1), 51, 2018, doi:10.1186/s12940-018-0392-z.


BACKGROUND: Glyphosate, formulated as Roundup, is the world’s most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate’s health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a “probable human carcinogen”. A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty.

REGULATORY ACTIONS: Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies.

RAMAZZINI INSTITUTE RESPONSE: The Ramazzini Institute has initiated a pilot study of glyphosate’s health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects. FULL TEXT

Laugeray et al., 2014

Anthony Laugeray, Ameziane Herzine, Olivier Perche,1,2 Betty Hébert, Marine Aguillon-Naury, Olivier Richard, Arnaud Menuet, Séverine Mazaud-Guittot, Laurianne Lesné, Sylvain Briault, Bernard Jegou, Jacques Pichon, Céline Montécot-Dubourg, and Stéphane Mortaud, “Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice,” Frontiers in Behavioral Neuroscience, 2014, 8:390, DOI: 10.3389/fnbeh.2014.00390


Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.  FULL TEXT

Lebov et al., 2015

Jill F. Lebov, MSPH, PhD, Lawrence S. Engel, PhD, David Richardson, PhD, Susan L. Hogan, PhD, Jane A. Hoppin, ScD, and Dale P. Sandler, PhD, “Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study,” Occupational and Environmental Medicine, 2016, 7, DOI: 10.1136/oemed-2014-102615


OBJECTIVES: Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 41 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.

METHODS: Via linkage to the United States Renal Data System, we identified 320 ESRD cases diagnosed between enrollment (1993-1997) and December 2011 among 55,580 male licensed pesticide applicators. Participants provided pesticide use information via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: 1) ordinal categories of intensity-weighted lifetime use of 41 pesticides, 2) poisoning and high-level pesticide exposures, and 3) pesticide exposure resulting in a medical visit or hospitalization.

RESULTS: Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide chlordane. More than one medical visit due to pesticide use (HR = 2.13; 95% CI: 1.17, 3.89) and hospitalization due to pesticide use (HR = 3.05; 95% CI: 1.67, 5.58) were significantly associated with ESRD.

CONCLUSIONS: Our findings support an association between ESRD and chronic exposure to specific pesticides and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD. FULL TEXT

Lim et al., 2009

Soo Lim, Sun Young Ahn, In Chan Song, Myung Hee Chung, Hak Chul Jang, Kyong Soo Park, Ki-Up Lee, Youngmi Kim Pak , Hong Kyu Lee, “Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance,” PLOS One, 2009, 4:4, DOI: 10.1371/journal.pone.0005186


There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent. FULL TEXT

Manikkam et al., 2013

Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna, Michael K. Skinner , “Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations,”  PLoS ONE, January 24, 2013, 8:1, DOI: 10.1371/journal.pone.0055387


Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures. FULL TEXT