Glyphosate and Non-Carcinogenicity

Comprehensive long-term toxicological studies repeated over the last 30 years have time and again demonstrated that glyphosate is unlikely to pose a cancer risk in humans. The U.S. EPA groups glyphosate in the lowest and most favorable category, E, indicating evidence of non-carcinogenicity for humans.

We have highlighted and included summaries from some key publications that demonstrate the safety of glyphosate when used according to label instructions. We have also included a list of many publications and documents publicly available that discuss human exposure to glyphosate; epidemiology and glyphosate, glyphosate and the lack of genotoxicity and carcinogenicity as well as many government and World Heath Organization reviews of glyphosate.   


Key Glyphosate Publications

 

Greim, H., D. Saltmiras, V. Mostert, and C. Strupp (2015). Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies. Crit. Rev. Toxicol.

http://informahealthcare.com/doi/abs/10.3109/10408444.2014.1003423

Summary: A new scientific publication examining 14 separate cancer studies in rats and mice conducted over the last several decades concludes that there is no evidence that glyphosate, the active ingredient in Roundup branded herbicides, causes cancer. The article, in Critical Reviews in Toxicology, evaluated the data from these long-term studies to determine whether there were any patterns to suggest humans exposed to glyphosate would have any concern about developing cancer. Other scientifically relevant information such as expert regulator evaluations, human dietary exposures and epidemiological studies were also discussed. The clear and consistent view across more than 30 years of relevant information continues to support the first expert opinions from the 1980s, that glyphosate does not cause cancer. 

 

Sorahan, T. (2015). Multiple Myeloma and Glyphosate Use: A Re-Analysis of US Agricultural Health Study (AHS) Data. Int. J. Environ. Res. Public Health

http://www.ncbi.nlm.nih.gov/pubmed/25635915

Summary: A new look at data from the US Agricultural Health Study (AHS) clarifies that there is no relationship between glyphosate use and the risk of multiple myeloma, a type of cancer.  The article considered data collected from over 57,000 pesticide applicators to determine whether a relationship exists between multiple myeloma and glyphosate exposure.  These results contradict the outcome of a previous analysis of AHS data that relied on a restricted data set to reach a different conclusion. This reanalysis of the full AHS data set for multiple myeloma is consistent with other epidemiological and laboratory research that demonstrated glyphosate does not cause cancer.

 

Kier, L. D. (2015). Review of Genotoxicity Biomonitoring Studies of Glyphosate-Based Formulations. Crit. Rev. Toxicol.

http://www.ncbi.nlm.nih.gov/pubmed/25687244

Summary: Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs (Kier and Kirkland, 2013). The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.

 

Kier, LD and DJ. Kirkland (2013). Review of genotoxicity studies of glyphosate and glyphosate-based formulations. Crit. Rev. Toxicol. 43:283.

http://www.ncbi.nlm.nih.gov/pubmed/23480780

Summary:  An earlier review of the toxicity of glyphosate and the original Roundup -branded formulation (Williams et al., 2000) concluded that neither glyphosate nor the formulation poses a risk for the production of heritable/somatic mutations in humans. The present review of subsequent genotoxicity publications and regulatory studies of glyphosate and glyphosate-based formulations (GBFs) incorporates all of the findings into a weight of evidence for genotoxicity. Glyphosate and typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.

 

Mink, P., J. Mandel, B. Sceurman, J. Lundin (2012). Epidemiologic studies of glyphosate and cancer: A review. Regul. Toxicol. Pharm. 63:3.

http://www.sciencedirect.com/science/article/pii/S0273230012000943

Summary:  A review of 21 epidemiological studies found no causal relationship between exposure to glyphosate and cancer in adults or children.  This observation is consistent with conclusions from regulatory authorities that glyphosate is unlikely to pose a risk to human health based on previous toxicology studies.

 

Niemann, L., C. Sieke, R. Pfeil, R. Solecki (2015). A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers. J. Consum. Protect. Food Safety.

http://rd.springer.com/article/10.1007%2Fs00003-014-0927-3

Summary:   The German Federal Institute for Risk Assessment reviewed seven existing biomonitoring studies where trace amounts of glyphosate were found in human urine samples. The authors concluded that at the levels of glyphosate found, there is no concern for human health. After oral intake glyphosate is not metabolized significantly by humans and is rapidly excreted in urine. By measuring urine levels it is possible to calculate internal exposure levels.  They concluded that realistic exposures are low and are well below the worst-case assumptions used by regulatory agencies.

 

 

Additional Glyphosate Publications

Exposure

  • Acquavella J.F.,  B. H. Alexander, J. S.  Mandel, C. Gustin, B. Baker, P.  Chapman, and M. Bleeke.  2004.   Glyphosate biomonitoring for farmers and their families:  Results from the Farm Family Exposure Study.  Environmental Health Perspectives 112(3):  321-326.  . 
  • EFSA European Food Safety Authority, 2014. The 2012 European Union Report on pesticide residues in food. EFSA Journal 2014;12(12):3942. http://www.efsa.europa.eu/en/efsajournal/doc/3942.pdf.
  • Fact Sheet - Residual Traces of Pesticide Residues including Glyphosate Residues in Food on the European Market Extracted from the 2012 European Union Report on pesticide residues in food (2014).
  • Lavy T, Cowell J, Steinmetz JR, Massey JH. 1992. Conifer seedling nursery exposure to glyphosate. Arch Environ Contam Toxicol 22:6-13.
  • Jönsson J., R. Camm, and T.Hall. (2013) Removal and degradation of glyphosate in water treatment: a review. Journal of Water Supply: Research and Technology—AQUA, 62 (7): 395-408.
  • Speth T.F.  (1994)  Glyphosate removal from drinking water.  Journal of Environmental Engineering  119: 1139-1157.

Epidemiology

  • Acquavella J, D. Farmer, and M. R. Cullen 1999. A case-control study of non-Hodgkin lymphoma and exposure to pesticides. Cancer 86:729-31.
  • Acquavella, J., J. R. Cowell, M. R. Cullen, D. R. Farmer, and H. Pastides.  2001.  Implications of glyphosate toxicology and human biomonitoring data for epidemiological research. Journal of Agromedicine 7(4): 7-27.
  • Acquavella, J., J. Doe, J. Tomenson, G. Chester, J. Cowell and L. Bloemen. 2003. Epidemiologic studies of occupational pesticide exposure and cancer; regulatory risk assessments and biologic plausibility. Ann Epidemiol 13:1-7.
  • Acquavella, J. F., C. Gustin, B. H. Alexander and J. S. Mandel. 2005. Implications for epidemiologic research on variation by pesticide in studies of farmers and their families. Scand J Work Environ Health 31 Suppl 1:105-109.
  • Acquavella, J., B. H. Alexander, J. S. Mandel, C. J. Burns and C. Gustin. 2006. Exposure misclassification in studies of agricultural pesticides. Insights from biomonitoring. Epidemiology 17:69-74.
  • Alexander, D. D., P. J. Mink, H. O. Adami, E. T. Chang, P. Cole, J. S. Mandel, and D. Trichopoulos. 2007. The non-Hodgkin lymphomas: a review of the epidemiologic literature. Int J Cancer 120 Suppl 12:1-39.
  • Armitage , J.O. 1997. The changing classification of non-Hodgkin’s lymphomas. CA Cancer J Clin 47:323–325.
  • Balshem, H., M. Helfand, H. J. Schunemann, A. D. Oxman, R. Kunz, J. Brozek, G. E. Vist, Y. Falck-Ytter, J. Meerpohl, S. Norris, and G. H. Guyatt. 2011. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 64:401-406.
  • Blair, A., and L. B. Freemen. 2009. Epidemiologic studies in agricultural populations: observations and future directions.  Journal of Agromedicine 14:125-131.
  • Blair, A., R. Tarone, D. Sandler, C. F. Lynch, A. Rowland, W. Wintersteen, W. C. Steen, C. Samanic, M. Dosemeci, and M. C. Alavanja. 2002. Reliability of reporting on life-style and agricultural factors by a sample of participants in the Agricultural Health Study from Iowa. Epidemiology 13:94-99.
  • Blair, A. and S. H. Zahm. 1990. Methodologic issues in exposure assessment for case-control studies of cancer and herbicides. Am J Ind Med 18:285-293.
  • Bowling, A. 2005. Mode of questionnaire administration can have serious effects on data quality. J Public Health (Oxf) 27:281-291.
  • Brown, L. M., A. Blair, R. Gibson, G. D. Everett, K. P. Cantor, L. M. Schuman, L. F. Burmeister, S. F. Van Lier, and F. Dick. 1990. Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. Cancer Res 50:6585-6591.
  • Brown, L. M., L. F. Burmeister, G. D. Everett, and A. Blair. 1993. Pesticide exposures and multiple myeloma in Iowa men. Cancer Causes Control 4:153-156.
  • Cantor, K. P., A. Blair, L. M. Brown, L. F. Burmeister, and G. Everett. 1993. Correspondence re: K. P. Cantor et al., pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota. Cancer Res 53:2421.
  • Cantor, K. P., A. Blair, G. Everett, R. Gibson, L. F. Burmeister, L. M. Brown, L. Schuman, and F. R. Dick. 1992. Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota. Cancer Res 52:2447-2455.
  • Cocco, P., G. Satta, S. Dubois, C. Pili, M. Pilleri, M. Zucca, A. M. t Mannetje, N. Becker, Y. Benavente, S. de Sanjose, L. Foretova, A. Staines, M. Maynadie, A. Nieters, P. Brennan, L. Miligi, M. G. Ennas, and P. Boffetta. 2013. Lymphoma risk and occupational exposure to pesticides: results of the Epilymph study. Occup Environ Med 70:91-98.
  • De Roos, A. J., A. Blair, J. A. Rusiecki, J. A. Hoppin, M. Svec, M. Dosemeci, D. P. Sandler, and M. C. Alavanja. 2005. Cancer incidence among glyphosate-exposed pesticide applicators in the Agricultural Health Study. Environ Health Perspect 113:49-54.
  • De Roos, A. J., S. H. Zahm, K. P. Cantor, D. D. Weisenburger, F. F. Holmes, L. F. Burmeister, and A. Blair. 2003. Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men. Occup Environ Med 60:E11.
  • De Roos, A. J., M. A. Svec,  A. Blair, J. A. Rusiecki, M. Dosemeci, M. C. Alavanja, J. A. Hoppin, and D. P. Sandler. 2005a.  Glyphosate Results Revisited: De Roos et al. Respond. Environ Health Perspect 113:49-54.
  • Eriksson, M., L. Hardell, M. Carlberg, and M. Akerman. 2008. Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis. Int J Cancer 123:1657-1663.
  • Farmer, D. R., T. L. Lash, and J. F. Acquavella. 2005. Glyphosate results revisited. Environmental Health Perspectives 113(6):A365-367.
  • Freeman, L. B. 2009. Evaluation of Agricultural Exposures: The Agricultural Health Study and the Agricultural Cohort Consortium. President's Cancer Panel - October 21, 2008. Reviews on Environmental Health 24 (4):311-318.
  • Griffith, L. E., D. J. Cook, G. H. Guyatt, and C. A. Charles. 1999. Comparison of open and closed questionnaire formats in obtaining demographic information from Canadian general internists. J Clin Epidemiol 52:997-1005.
  • Hardell, L. and M. Eriksson. 1999. A case-control study of non-Hodgkin lymphoma and exposure to pesticides. Cancer 85:1353-1360.
  • Hardell, L., M. Eriksson, and M. Nordstrom. 2002. Exposure to pesticides as risk factor for non-Hodgkin's lymphoma and hairy cell leukemia: pooled analysis of two Swedish case-control studies. Leuk Lymphoma 43:1043-1049.
  • Higgins, J. P. T. and S. Green, editors. 2011. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. [updated March 2011)]. Available at: www.cochrane-handbook.org. The Cochrane Collaboration.
  • Hill, A. B. 1965. The Environment and Disease: Association or Causation? Proc R Soc Med 58:295-300.
  • Hohenadel, K., S. A. Harris, J. R. McLaughlin, J. J. Spinelli, P. Pahwa, J. A. Dosman, P. A. Demers, and A. Blair. 2011. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces. Int J Environ Res Public Health 8:2320-2330.
  • Jurek, A. M., S. Greenland, and G. Maldonado. 2008. How far from non-differential does exposure or disease misclassification have to be to bias measures of association away from the null? Int J Epidemiol 37:382-385.
  • Jurek, A. M., S. Greenland, G. Maldonado, and T. R. Church. 2005. Proper interpretation of non-differential misclassification effects: expectations vs observations. Int J Epidemiol 34:680-687.
  • Kachuri, L., P. A. Demers, A. Blair, J. J. Spinelli, M. Pahwa, J. R. McLaughlin, P. Pahwa, J. A. Dosman, and S. A. Harris. 2013. Multiple pesticide exposures and the risk of multiple myeloma in Canadian men. Int J Cancer 133:1846-1858.
  • Karunanayake, C. P., J. J. Spinelli, J. R. McLaughlin, J. A. Dosman, P. Pahwa, and H. H. McDuffie. 2012. Hodgkin lymphoma and pesticides exposure in men: a Canadian case-control study. J Agromedicine 17:30-39.
  • Kaufman, D. W., T. E. Anderson, and S. Issaragrisil. 2009. Risk factors for leukemia in Thailand. Ann Hematol 88:1079-1088.
  • Landgren, O., R. A. Kyle, J. A. Hoppin, L. E. Beane Freeman, J. R. Cerhan, J. A. Katzmann, S. V. Rajkumar, and M. C. Alavanja. 2009. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood 113:6386-6391.
  • Lash, T. L. 2007. Bias analysis applied to Agricultural Health Study publications to estimate non-random sources of uncertainty. Journal of Occupational Medicine and Toxicology  2(15): 1-9.
  • Lee, W. J., K. P. Cantor, J. A. Berzofsky, S. H. Zahm, and A. Blair. 2004a. Non-Hodgkin's lymphoma among asthmatics exposed to pesticides. Int J Cancer 111:298-302.
  • Mandel, J. S., B. H. Alexander, B. A. Baker, J. F. Acquavella, P. Chapman, and R. Honeycutt. 2005. Biomonitoring for farm families in the Farm Family Exposure Study. Scand J Work Environ Health 31 Suppl 1: 98-104.
  • McDuffie, H. H., P. Pahwa, J. R. McLaughlin, J. J. Spinelli, S. Fincham, J. A. Dosman, D. Robson, L. F. Skinnider, and N. W. Choi. 2001. Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health. Cancer Epidemiol Biomarkers Prev 10:1155-1163.
  • Mink, P.J.,  J. S. Manderl, J. I. Lundin and B. K. Sceurman. 2011. Epidemiologic studies of glyphosate and non-cancer health out comes: a review. Regul Toxicol Pharmacol  61:172-184.
  • Nordstrom, M., L. Hardell, A. Magnuson, H. Hagberg, and A. Rask-Andersen. 1998. Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study. Br J Cancer 77:2048-2052.
  • Orsi, L., L. Delabre, A. Monnereau, P. Delval, C. Berthou, P. Fenaux, G. Marit, P. Soubeyran, F. Huguet, N. Milpied, M. Leporrier, D. Hemon, X. Troussard, and J. Clavel. 2009. Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study. Occup Environ Med 66:291-298.
  • Pahwa, P., C. P. Karunanayake, J. A. Dosman, J. J. Spinelli, H. H. McDuffie, and J. R. McLaughlin. 2012. Multiple myeloma and exposure to pesticides: a Canadian case-control study. J Agromedicine 17:40-50.
  • Pearce, N. and D. McLean. 2005. Agricultural exposures and non-Hodgkin's lymphoma. Scand J Work Environ Health 31 Suppl 1:18-25; discussion 15-17.
  • Schinasi, L. and M. E. Leon. 2014. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis. Int J Environ Res Public Health 11:4449-4527.
  • Weichenthal, S., C. Moase, and P. Chan. 2010. A review of pesticide exposure and cancer incidence in the Agricultural Health Study Cohort. Environmental Health Perspectives 118 (8): 1117-1125.

Toxicology Studies

  • Heydens, W. F., C. E. Healy, K. J. Hotz, L. D. Kier, M. A. Martens, A. G. E. Wilson and D. R. Farmer. 2008. Genotoxic potential of glyphosate formulations: mode-of-action investigations. J. Agric. Food Chem. 56:1517-1523.
  • Williams, G. M , R. Kroes and I. C. Munro. 2000. Regulatory Toxicology and Pharmacology. 31: 117-165. 
  • Levine, S. L., Z. Han, J. Liu, D. R. Farmer and V. Papadopoulos. 2007. Disrupting mitochondrial function with surfactants inhibits MA-10 Leydig cell steroidogenesis. Cell Biol Toxicol 23:385-400.

Regulatory and Government Documents

  • US EPA.  1993.  Reregistration Eligibility Decision (RED):  Glyphosate.  Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Washington, DC. 
  • US EPA. 2013 Federal Register Final Rule Glyphosate; Pesticide Tolerances. 78 (84): 25396-25401.  The following documents provide the assessments behind this final rule:
    • US EPA. 2012. Human Health Risk Assessment (EPA–HQ–OPP–2012–0132-0010). Glyphosate. Section 3 Registration Concerning the Application of Glyphosate to Carrots, Sweet Potato, Teff, and Oilseeds (Crop Group (CG) 20) and to Update the CG Definitions for Bulb Vegetable (CG 3–07), Fruiting Vegetable (CG 8–10), Citrus Fruit (CG 10–10), Pome Fruit (CG 11–10), and Berry (CG 13–07).
    • US EPA. 2012. Drinking Water Assessment (EPA-HQ-OPP-2012-0132-0013) for Label Amendments (Roundup WeatherMAX® EPA Reg. No. 524-537 and Roundup Ultra® EPA Reg. No. 524-475) for Glyphosate Use on Oilseed Crops, Root and Tuber Crops, Pome Fruit Crops, Citrus Fruit Crops, Fruiting Vegetable Crops, Berry and Small Fruit Crops, Bulb Vegetables Crops.
    • US EPA. 2012. Dietary Exposure and Risk Assessment (EPA-HQ-OPP-2012-0132-0011) in Support of the Requested Application of Glyphosate to Carrots, Sweet Potatoes, and Oilseeds (Crop Group (CG) 20) and to Update the CG Definitions for Bulb Vegetable (CGT 3-07), Fruiting Vegetable (CG 8-10), Citrus Fruit (CG 10-10), Pome Fruit (CG 11-10), and Berry (CG 13-07).
  • Canada Pest Management Regulatory Agency.  1991.  Pre-Harvest use of glyphosate herbicide [Preharvest application of glyphosate (Roundup) herbicide].  Discussion Document D91-01.  98 pp.  Pesticide Information Division, Plant Industry Directorate, Agriculture Canada.
  • JMPR (WHO/FAO). 1986.  Pesticides residues in food. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. Part II-Toxicology, Glyphosate: 63-76. Rome, Italy, 29 September – 8 October.
  • JMPR (WHO/FAO).  2004.  Pesticide Residues in Food.  Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group. Part II-Toxicology, Glyphosate: 96-169.  Rome, Italy 20-29 September 2004.
  • JMPR (WHO/FAO) .  2004.  Pesticide Residues in Food.  Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues. FAO Plant Production and Protection Paper 178, Glyphosate Dietary Risk Assessment: 98-103.  Rome, Italy 20-29 September 2004.
  • World Health Organization (WHO).  1994.  Glyphosate. International Programme on Chemical Safety, Environmental Health Criteria No. 159.  World Health Organization, Geneva. 
  • World Health Organization (WHO).  2005.  Glyphosate and AMPA in Drinking-water.  Background document for development of WHO Guidelines for Drinking-water Qualty.
  • European Commission.  (2002)  Report for the Active Substance Glyphosate, Directive 6511/VI/99, January 21.
  • Australian Pesticides and Veterinary Medicines Authority (APVMA).2013. A review of the Earth Open Source (EOS) report.
  • Germany Federal Institute for Risk Assessment (BFR)  - Update on glyphosate review. 2015.
  • Germany Federal Institute for Risk Assessment (BfR) Annex 1 Renewal Assessment Report Glyphosate
  • EFSA European Food Safety Authority Final review of the Séralini et al. 2012a publication on a 2-year rodent feeding study with glyphosate formulations and GM maize NK603 published online 19 September 2012 in Food and chemical Toxicology. EFSA Journal 2012 10(11):2986. http://www.efsa.europa.eu/en/search/doc/2986.pdf
  • ANSES National Agency for Food, Environmental and Occupational Health Safety. 2014. SCIENTIFIC AND TECHNICAL SUPPORT MEMORANDUM on the analysis of the differences between ‘Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’ by Séralini et al. (2014) and the original publication of said study in 2012.
  • Germany Federal Institute for Risk Assessment (BfR) opinion on Seralini et al. 2012 “Feeding study in rats with genetically modified NK603 maize and with a glyphosate containing formulation (Roundup) published by Séralini et al. (2012)” http://www.bfr.bund.de/cm/349/feeding-study-in-rats-with-genetically-modified-nk603-maize-and-with-a-glyphosate-containing-formulation-roundup-published-bei-seralini-et-al-2012.pdf
  • Food Standards Australia New Zealand FSANZ. 2013. Response to Seralini paper.