Bibliography Tag: cancer risks

Alavanja et al., 2004

Alavanja, M. C., Hoppin, J. A., & Kamel, F.; “Health effects of chronic pesticide exposure: cancer and neurotoxicity;” Annual review of public health, 2004, 25, 155-197; DOI: 10.1146/annurev.publhealth.25.101802.123020.


Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers. FULL TEXT

Blair et al., 1985

Blair, A., Malker, H., Cantor, K. P., Burmeister, L., & Wiklund, K.; “Cancer among farmers. A review;” Scandinavian Journal of Work, Environment, & Health, 1985, 11(6), 397-407; DOI: 10.5271/sjweh.2208.


During the performance of routine tasks farmers may come in contact with a variety of substances, including pesticides, solvents, oils and fuels, dusts, paints, welding fumes, zoonotic viruses, microbes, and fungi. Because some of these substances are known or suspected carcinogens, the epidemiologic literature regarding cancer risks concerning farmers has been reviewed. Farmers had consistent deficits for cancers of the colon, rectum, liver, and nose. The deficits for cancer of the lung and bladder were particularly striking, presumably due to less frequent use of tobacco among farmers than among people in many other occupational groups. Malignancies frequently showing excesses among farmers included Hodgkin’s disease, leukemia, non-Hodgkin’s lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, skin (nonmelanotic), brain, and connective tissues. The etiologic factors that may contribute to these excesses in the agricultural environment have not been identified. Detailed, analytic epidemiologic studies that incorporate environmental and biochemical monitoring are needed to clarify these associations. FULL TEXT

Blair and Zahm, 1993

Blair, A., & Zahm, S. H.; “Patterns of pesticide use among farmers: implications for epidemiologic research;” Epidemiology, 1993, 4(1), 55-62; DOI: 10.1097/00001648-199301000-00011.


Epidemiologic studies of farmers have linked pesticides with certain cancers. Information on exposures from many of these studies was obtained by interview of farmers or their next-of-kin. The reliability and validity of data on pesticide use obtained by recall, often years after the event, have been questioned. Pesticide use, however, is an integral component in most agricultural operations, and the farmers’ knowledge and recall of chemicals used may be better than for many other occupations. Contrary to general belief, many farmers typically use only a few pesticides during their lifetimes and make only a few applications per year. Data from U.S. Department of Agriculture surveys indicate that herbicides are applied to wheat, corn, soybeans, and cotton and that application of insecticides to corn averages two or fewer times per year. In epidemiologic studies at the National Cancer Institute, the proportion of farmers ever reporting lifetime use of five or more different chemicals was 7% for insecticides and 20% for herbicides. Surrogate respondents have often been used in epidemiologic studies of cancer; they are able to recall pesticide use with less detail than the farmers themselves. The pesticides reported by surrogates were the same as reported by subjects themselves, but with less frequency. Comparison of reporting by cases and controls provided no evidence of case-response (differential) bias; thus, inaccurate recall of pesticide use by subjects or surrogates would tend to diminish risk estimates and dilute exposure-response gradients. FULL TEXT

Blair et al., 1992

Blair, A., Zahm, S. H., Pearce, N. E., Heineman, E. F., & Fraumeni, J. F., Jr.; “Clues to cancer etiology from studies of farmers;” Scandinavian Journal of Work, Environment, & Health, 1992, 18(4), 209-215; DOI: 10.5271/sjweh.1578.


This article summarizes cancer risks among farmers to clarify the magnitude of the problem and to suggest directions for future research. Significant excesses occurred for Hodgkin’s disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin’s lymphoma and cancers of connective tissue and brain. These excesses occurred against a background of substantial deficits among farmers for total mortality and mortality from many specific diseases. The tumors vary in frequency, histology, and prognosis and do not fall into any obvious grouping. Two commonalities may be important. Several of the tumors excessive among farmers appear to be rising in the general population and are excessive among patients with naturally occurring or medically induced immunodeficiencies. Therefore epidemiologic studies on specific exposures among farmers may help explain the rising trend of certain cancers in developed countries and provide clues to mechanisms of action for environmental carcinogens. FULL TEXT


Alavanja et al., 2004

Alavanja, M. C., Dosemeci, M., Samanic, C., Lubin, J., Lynch, C. F., Knott, C., Barker, J., Hoppin, J. A., Sandler, D. P., Coble, J., Thomas, K., & Blair, A.; “Pesticides and lung cancer risk in the agricultural health study cohort;” American Journal of Epidemiology, 2004, 160(9), 876-885; DOI: 10.1093/aje/kwh290.


The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; p(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p(trend) = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; p(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p(trend) = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time. FULL TEXT

Benbrook, 2020

Benbrook, Charles; “Shining a Light on Glyphosate-Based Herbicide Hazard, Exposures and Risk: Role of Non-Hodgkin Lymphoma Litigation in the USA;” European Journal of Risk Regulation, 2020, 11(3), 498-519; DOI: 10.1017/err.2020.16.


Roundup, and other glyphosate-based herbicides, are the most heavily used pesticides in the history of the USA and globally. In March 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a “probable human carcinogen”. A portion of the 695,000 Americans then living in 2015 with non-Hodgkin lymphoma (NHL) became aware of IARC’s decision. Several thousand Roundup–NHL lawsuits had been filed by the end of 2017, rising to 18,400 by July 2019 and 42,000 by November 2019. Three cases have gone to trial, each won by the plaintiffs. The author has served as an expert witness for the plaintiffs in this litigation and has been compensated for his time spent. The impact of the litigation on the independent assessment of the science useful in determining whether glyphosate and glyphosate-based herbicide exposures are linked to NHL is reviewed, as is why the US Environmental Protection Agency (EPA) and IARC reached such different judgements regarding glyphosate human cancer hazard and risk. Two important “lessons learned” regarding the EPA versus IARC assessment of glyphosate cancer hazard and risk are highlighted. The first arises from differences in the magnitude of applicator risks from mostly dermal exposures to formulated glyphosate-based herbicides compared to just dietary exposures to technical glyphosate. The second relates to missed opportunities to markedly lower applicator exposures and risks with little or no impact on sales via reformulation, added warnings and worker safety provisions, company-driven stewardship programmes and greater determination by the EPA in the 1980s to compel Monsanto to add common-sense worker protection provisions onto Roundup labels (eg “wear gloves when applying this product”). Policy reforms designed to alleviate systemic problems with how pesticide hazards, exposures and risks are analysed, regulated and mitigated are described. FULL TEXT

Connolly et al., 2020

Connolly, A., Coggins, M. A., & Koch, H. M.; “Human Biomonitoring of Glyphosate Exposures: State-of-the-Art and Future Research Challenges;” Toxics, 2020, 8(3); DOI: 10.3390/toxics8030060.


Glyphosate continues to attract controversial debate following the International Agency for Research on Cancer carcinogenicity classification in 2015. Despite its ubiquitous presence in our environment, there remains a dearth of data on human exposure to both glyphosate and its main biodegradation product aminomethylphosphonic (AMPA). Herein, we reviewed and compared results from 21 studies that use human biomonitoring (HBM) to measure urinary glyphosate and AMPA. Elucidation of the level and range of exposure was complicated by differences in sampling strategy, analytical methods, and data presentation. Exposure data is required to enable a more robust regulatory risk assessment, and these studies included higher occupational exposures, environmental exposures, and vulnerable groups such as children. There was also considerable uncertainty regarding the absorption and excretion pattern of glyphosate and AMPA in humans. This information is required to back-calculate exposure doses from urinary levels and thus, compared with health-based guidance values. Back-calculations based on animal-derived excretion rates suggested that there were no health concerns in relation to glyphosate exposure (when compared with EFSA acceptable daily intake (ADI)). However, recent human metabolism data has reported as low as a 1% urinary excretion rate of glyphosate. Human exposures extrapolated from urinary glyphosate concentrations found that upper-bound levels may be much closer to the ADI than previously reported. FULL TEXT

Meftaul et al.; 2020

Meftaul, I. M., Venkateswarlu, K., Dharmarajan, R., Annamalai, P., Asaduzzaman, M., Parven, A., & Megharaj, M.; “Controversies over human health and ecological impacts of glyphosate: Is it to be banned in modern agriculture?;” Environmental Pollution, 2020, 263(Pt A), 114372; DOI: 10.1016/j.envpol.2020.114372.


Glyphosate, introduced by Monsanto Company under the commercial name Roundup in 1974, became the extensively used herbicide worldwide in the last few decades. Glyphosate has excellent properties of fast sorption in soil, biodegradation and less toxicity to nontarget organisms. However, glyphosate has been reported to increase the risk of cancer, endocrine-disruption, celiac disease, autism, effect on erythrocytes, leaky-gut syndrome, etc. The reclassification of glyphosate in 2015 as ‘probably carcinogenic’ under Group 2A by the International Agency for Research on Cancer has been broadly circulated by anti-chemical and environmental advocacy groups claiming for restricted use or ban of glyphosate. In contrast, some comprehensive epidemiological studies involving farmers with long-time exposure to glyphosate in USA and elsewhere coupled with available toxicological data showed no correlation with any kind of carcinogenic or genotoxic threat to humans. Moreover, several investigations confirmed that the surfactant, polyethoxylated tallow amine (POEA), contained in the formulations of glyphosate like Roundup, is responsible for the established adverse impacts on human and ecological health. Subsequent to the evolution of genetically modified glyphosate-resistant crops and the extensive use of glyphosate over the last 45 years, about 38 weed species developed resistance to this herbicide. Consequently, its use in the recent years has been either restricted or banned in 20 countries. This critical review on glyphosate provides an overview of its behaviour, fate, detrimental impacts on ecological and human health, and the development of resistance in weeds and pathogens. Thus, the ultimate objective is to help the authorities and agencies concerned in resolving the existing controversies and in providing the necessary regulations for safer use of the herbicide. In our opinion, glyphosate can be judiciously used in agriculture with the inclusion of safer surfactants in commercial formulations sine POEA, which is toxic by itself is likely to increase the toxicity of glyphosate. FULL TEXT

Williams et al., 2000

Williams, G. M., Kroes, R., & Munro, I. C.; “Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans;” Regulatory Toxicology and Pharmacology, 2000, 31(2 Pt 1), 117-165; DOI: 10.1006/rtph.1999.1371.


Reviews on the safety of glyphosate and Roundup herbicide that have been conducted by several regulatory agencies and scientific institutions worldwide have concluded that there is no indication of any human health concern. Nevertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evaluation and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Roundup formulations, and the predominant surfactant [polyethoxylated tallow amine (POEA)] used in Roundup formulations worldwide. The studies evaluated in this review included those performed for regulatory purposes as well as published research reports. The oral absorption of glyphosate and AMPA is low, and both materials are eliminated essentially unmetabolized. Dermal penetration studies with Roundup showed very low absorption. Experimental evidence has shown that neither glyphosate nor AMPA bioaccumulates in any animal tissue. No significant toxicity occurred in acute, subchronic, and chronic studies. Direct ocular exposure to the concentrated Roundup formulation can result in transient irritation, while normal spray dilutions cause, at most, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation criteria. There was no convincing evidence for direct DNA damage in vitro or in vivo, and it was concluded that Roundup and its components do not pose a risk for the production of heritable/somatic mutations in humans. Multiple lifetime feeding studies have failed to demonstrate any tumorigenic potential for glyphosate. Accordingly, it was concluded that glyphosate is noncarcinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmentally toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with glyphosate. Likewise there were no adverse effects in reproductive tissues from animals treated with glyphosate, AMPA, or POEA in chronic and/or subchronic studies. Results from standard studies with these materials also failed to show any effects indicative of endocrine modulation. Therefore, it is concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals. For purposes of risk assessment, no-observed-adverse-effect levels (NOAELs) were identified for all subchronic, chronic, developmental, and reproduction studies with glyphosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculated for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of oral LD50 values to estimated maximum acute human exposure. It was concluded that, under present and expected conditions of use, Roundup herbicide does not pose a health risk to humans.

Christensen et al., 2016

Christensen, C. H., Barry, K. H., Andreotti, G., Alavanja, M. C., Cook, M. B., Kelly, S. P., Burdett, L. A., Yeager, M., Beane Freeman, L. E., Berndt, S. I., & Koutros, S.; “Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study;” Frontiers in Oncology, 2016, 6, 237; DOI: 10.3389/fonc.2016.00237.


Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 x 10(-5); q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk. FULL TEXT