Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies

References

• Acquavella JF, Alexander BH, Mandel JS, Gustin C, Baker B, Chapman P, Bleeke M. (2004). Glyphosate biomonitoring for farmers and their families: Results from the farm family exposure study. Environ Health Perspect, 112, 321–6.
   PubMed Web of Science ®Google Scholar
• Adami HO, Berry SC, Breckenridge CB, Smith LL, Swenberg JA, Trichopoulos D, et al. (2011). Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference. Toxicol Sci, 122, 223–34.
   PubMed Web of Science ®Google Scholar
• Alavanja MC, Ross MK, Bonner MR (2013). Increased cancer burden among pesticide applicators and others due to pesticide exposure. CA Cancer J Clin, 63, 120–42.
   PubMed Web of Science ®Google Scholar
• Anadon A, Martinez-Larranaga MR, Martinez MA, Castellano VJ, Martinez M, Martin MT, et al. (2009). Toxicokinetics of glyphosate and its metabolite aminomethyl phosphonic acid in rats. Toxicol Lett, 190, 91–5.
   PubMed Web of Science ®Google Scholar
• Antoniou M, Habib M, Howard C, Jennings R, Leifert C, Nodari R, et al. (2012). Teratogenic effects of glyphosate-based herbicides: divergence of regulatory decisions from scientific evidence. J Environ Anal Toxicol, S4, 006.
   Google Scholar
• Aris A, Leblanc S. (2011). Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada. Reprod Toxicol, 31, 528–33.
   PubMed Web of Science ®Google Scholar
• Aris A, Paris K. (2010). [Hypothetical link between endometriosis and xenobiotics-associated genetically modified food]. Gynecol Obstet Fertil, 38, 747–53.
   PubMed Web of Science ®Google Scholar
• Armitage JO. (1997). The changing classification of non-Hodgkin's lymphomas. CA Cancer J Clin, 47, 323–5.
   PubMed Web of Science ®Google Scholar
• Arysta Life Sciences. (1997a). HR-001: 18-Month Oral Oncogenicity Study in Mice. Tokyo, Japan: The Institute of Environmental Toxicology.
   Google Scholar
• Arysta Life Sciences. (1997b). HR-001: 24-Month Oral Chronic Toxicity and Oncogenicity Study in Rats. Kodaira-shi, Tokyo, Japan: The Institute of Environmental Toxicology.
   Google Scholar
• Arysta Life Sciences. (1997c). HR-001: 12-Month Oral Chronic Toxicity Study in Dogs. IET 94-0157
   Google Scholar
• Bailey J, Hauswirth J, Stump D. (2013). No evidence of endocrine disruption by glyphosate in male and female pubertal assays (Conference Abstract PS 1937). The Toxicologist (supplement to Toxicological Sciences), 132, 412.
   Google Scholar
• Barale-Thomas E. (2013). The SFPT feels compelled to point out weaknesses in the paper by Seralini et al. (2012). Food Chem Toxicol, 53, 473–4.
   PubMed Web of Science ®Google Scholar
• Benachour N, Seralini GE. (2009). Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol, 22, 97–105.
   PubMed Web of Science ®Google Scholar
• Berry C. (2013). Adverse effects in a feeding study of a GM derived corn in rats. Food Chem Toxicol, 53, 445–6.
   PubMed Web of Science ®Google Scholar
• Berry CL. (2010). Relativism, regulation and the dangers of indifferent science: the Sir Roy Cameron lecture of the Royal College of Pathologists. Toxicology, 267, 7–13.
   PubMed Web of Science ®Google Scholar
• Bradford Hill A. (1965). The environment and disease: association or causation? Proc R Soc Med, 58, 295–300.
   PubMedGoogle Scholar
• Bradley A, Mukaratirwa S, Petersen-Jones M. (2012). Incidences and range of spontaneous findings in the lymphoid and haemopoietic system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic toxicity studies. Toxicol Pathol, 40, 375–81.
   PubMed Web of Science ®Google Scholar
• Brayton CF, Treuting PM, Ward JM. (2012). Pathobiology of aging mice and GEM: background strains and experimental design. Vet Pathol, 49, 85–105.
   PubMed Web of Science ®Google Scholar
• Brock WJ. (2014). Strengthening the peer review process for the International Journal of Toxicology. Int J Toxicol, 33, 351–2.
   Web of Science ®Google Scholar
• Chandra M, Riley MG, Johnson DE. (1992). Spontaneous neoplasms in aged Sprague-Dawley rats. Arch Toxicol, 66, 496–502.
   PubMed Web of Science ®Google Scholar
• Cheminova. (1990). Glyphosate: 52 Week Oral Toxicity Study in Dogs. Inveresk Research International Report No.: 7502. Cheminova report No.: 52 GLY.
   Google Scholar
• Cheminova. (1993a). Glyphosate – 104 Week Combined Chronic Feeding/Oncogenicity Study in Rats with 52 Week Interim Kill (Results After 104 Weeks). Tranent, UK: Inveresk Research International, Ltd.
   Google Scholar
• Cheminova. (1993b). Glyphosate: 104 week dietary carcinogenicity study in mice. Tranent, UK: Inveresk Research International, Ltd.
   Google Scholar
• Chruscielska K, Brzezinski J, Kita K, Kalhorn D, Kita I, Graffstein B, et al. (2000a). Glyphosate – evaluation of chronic activity and possible far-reaching effects. Part 1. Studies on chronic toxicity. Pestycydy (Warsaw), 3–4, 11–20.
   Google Scholar
• Chruscielska K, Graffstein B, Szarapinska-Kwaszewska J, Brzezinski J, Kalhorn D. (2000b). Glyphosate: Evaluation of chronic activity and possible far-reaching effects. Part 2. Studies on mutagenic activity. Pestycydy (Warsaw) 3–4, 21–5.
   Google Scholar
• De Roos AJ, Blair A, Rusiecki JA, Hoppin JA, Svec M, Dosemeci M, et al. (2005). Cancer incidence among glyphosate-exposed pesticide applicators in the Agricultural Health Study. Environ Health Perspect, 113, 49–54. doi 10.1289/ehp.7340.
   PubMed Web of Science ®Google Scholar
• de Souza L, Oda LM. (2013). Letter to the editor. Food Chem Toxicol, 53, 440.
   PubMed Web of Science ®Google Scholar
• EC. (2002). Review report for the active substance glyphosate. European Commission., Directorate E – Food Safety: plant health, animal health and welfare, international questions, E1-Plant health.
   Google Scholar
• EFSA. (2012). Reasoned Opinion – Modification of the existing MRL for glyphosate in lentils. EFSA J, 10, 2250.
   Google Scholar
• Eriksson M, Hardell L, Carlberg M, Akerman M. (2008). Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis. Int J Cancer, 123, 1657–63.
   PubMed Web of Science ®Google Scholar
• EU. (2008). Council Regulation (EC) No 440/2008. Available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri = OJ:L:2008: 142:0001:0739:en:PDF. Accessed on November 13, 2012
   Google Scholar
• Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Foley GL, et al. (2013). Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol, 41, 560–614.
   PubMed Web of Science ®Google Scholar
• Excel. (1997). Combined Chronic Toxicity/Carcinogenicity Study of Glyphosate Technical in Sprague Dawley Rats. Pune, India: Indian Institute of Toxicology.
   Google Scholar
• Feinchemie Schwebda. (1996). Combined Chronic Toxicity and Carcinogenicity Study with Glyphosate Technical in Wistar Rats. Bangalore, India: Rallis India, Ltd.
   Google Scholar
• Feinchemie Schwebda. (2001). Carcinogenicity Study with Glyphosate Technical in Swiss Albino Mice. Bangalore, India: Rallis India, Ltd.
   Google Scholar
• Gad SC, Frith CH, Goodman DG, Boysen BG. (2008). Chapter 2. The Mouse. In: Gad, SC, Ed. Animal Models in Toxicology, Second Edition. Informa Health Care USA, Inc. ISBN-13: 978-0-8247-5407-5. ISBN-10: 0-8247-5407-7.
   Google Scholar
• Gasnier C, Benachour N, Clair E, Travert C, Langlois F, Laurant C, et al. (2010). Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines. J Occup Med Toxicol, 5, 29.
   PubMed Web of Science ®Google Scholar
• Germany Rapporteur Member State. (2015a). Glyphosate Renewal Assessment Report, Volume 1. Report and Proposed Decision. Revised 29th, January 2015.
   Google Scholar
• Germany Rapporteur Member State. (2015b). Glyphosate Renewal Assessment Report, Volume 3, Annex B.6.1 Toxicology and Metabolism. Revised 29th, January 2015.
   Google Scholar
• Germany Rapporteur Member State. (2015c). List of Endpoints, Active Substance Glyphosate. Report and Proposed Decision. Revised 29th, January 2015.
   Google Scholar
• Gold LS, Sawyer CB, Magaw R, Backman GM, de Veciana M, Levinson R, et al. (1984). A carcinogenic potency database of the standardized results of animal bioassays. Environ Health Perspect, 58, 9–319.
   PubMed Web of Science ®Google Scholar
• Grunewald W, Bury J. (2013). Comment on “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize” by Seralini et al. Food Chem Toxicol, 53, 447–8.
   PubMed Web of Science ®Google Scholar
• Hammond B, Goldstein DA, Saltmiras D. (2013). Response to original research article, in press, corrected proof, “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize’’. Food Chem Toxicol, 53, 459–64.
   PubMed Web of Science ®Google Scholar
• Hayes AW. (2014). Reply to letter to the editor: Editor in Chief of Food and Chemical Toxicology answers questions on retraction. Food Chem Toxicol, 65, 394–5.
   PubMed Web of Science ®Google Scholar
• IUPAC. (1997). Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997). XML on-line corrected version: http://goldbook.iupac.org (2006-) created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins. ISBN 0-9678550-9-8. doi:10.1351/goldbook. (http://goldbook.iupac.org/M03771.html).
   Google Scholar
• JMAFF. (2000). Data Requirements for Supporting Registration of Pesticides. Appendix, Section 2-1-15. Available at: http://www.acis.famic.go.jp/eng/shinsei/8147annex.pdf. Accessed on March 8, 2013.
   Google Scholar
• Johnson MD, Gad SC. (2008). Chapter 3. The Rat. In: Gad, SC, Ed. Animal Models in Toxicology, Second Edition. Informa Health Care USA, Inc. ISBN-13: 978-0-8247-5407-5. ISBN-10: 0-8247-5407-7.
   Google Scholar
• Kier LD, Kirkland DJ. (2013). Review of genotoxicity studies of glyphosate and glyphosate-based formulations. Crit Rev Toxicol, 43, 283–315.
   PubMed Web of Science ®Google Scholar
• Klimisch HJ, Andreae M, Tillmann U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul Toxicol Pharmacol, 25, 1–5.
   PubMed Web of Science ®Google Scholar
• Langridge P. (2013). Problems lie at several levels and bring into serious question the quality and standard of the editorial processes in your journal. Food Chem Toxicol, 53, 441.
   PubMed Web of Science ®Google Scholar
• Le Tien D, Le Huy H. (2013). Comments on “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize”. Food Chem Toxicol, 53, 443–4.
   PubMed Web of Science ®Google Scholar
• Levine S, Saltmiras D, Webb E, Holmes C, Mortensen S, Honegger J, Bailey J. (2012). Tier 1 EDSP Assays and Regulatory Safety Studies Provide a Weight of Evidence that Glyphosate is Not an Endocrine Disruptor (Conference Abstract 529). Abstract Book for SETAC North America 33rd Annual Meeting. Long Beach, California. November 11–15, 2012.
   Google Scholar
• Mink PJ, Mandel JS, Sceurman BK, Lundin JI. (2012). Epidemiologic studies of glyphosate and cancer: a review. Regul Toxicol Pharmacol, 63, 440–52.
   PubMed Web of Science ®Google Scholar
• Monsanto. (1981). A Lifetime Feeding Study of Glyphosate (ROUNDUP Technical) in Rats. East Millstone, New Jersey, USA: Bio/dynamics Inc.
   Google Scholar
• Monsanto. (1983). A Chronic Feeding Study of Glyphosate (Roundup^® Technical) in Mice. East Millstone, New Jersey, USA: Bio/dynamics, Inc.
   Google Scholar
• Monsanto. (1985). Twelve-month Study of Glyphosate administered by Gelatin Capsule to Beagle Dogs. Monsanto report ML-83-137.
   Google Scholar
• Monsanto. (1990). Chronic Study of Glyphosate Administered in Feed to Albino Rats. St. Louis, MO, USA: Monsanto Agricultural Company.
   Google Scholar
• Nolte T, Rittinghausen S, Kellner R, Karbe E, Kittel B, Rinke M, Deschl U. (2011). RITA–Registry of Industrial Toxicology Animal data: the application of historical control data for Leydig cell tumors in rats. Exp Toxicol Pathol, 63, 645–56.
   PubMed Web of Science ®Google Scholar
• Nufarm. (2007). Glyphosate technical: 52-week Toxicity Study by Oral Route (Capsule) in Beagle Dogs. Study No. 29647 TCC.
   Google Scholar
• Nufarm. (2009a). Glyphosate Technical: Dietary Carcinogenicity Study in the Mouse. Derbyshire, UK: Harlan Laboratories Ltd.
   Google Scholar
• Nufarm. (2009b). Glyphosate Technical: Dietary Combined Chronic Toxicity/Carcinogenicity in the Rat. Shardlow, Derbyshire, UK: Harlan Laboratories Ltd.
   Google Scholar
• OECD. (2012a). Guidance Document 116 on the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453, 2nd Edition. Available at: http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote = ENV/JM/MONO(2011)47&doclanguage = en. Accessed on 20th, January 2015.
   Google Scholar
• OECD. (2012b). OECD Guidelines for the Testing of Chemicals, Section 4 - Health Effects. Available at: http://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-of-chemicals-section-4-health-effects_20745788. Accessed on 20th, January 2015.
   Google Scholar
• Ollivier L. (2013). A comment on “Seralini, G.-E., et al., Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem. Toxicol. (2012)”. Food Chem Toxicol, 53, 458.
   PubMed Web of Science ®Google Scholar
• Paganelli A, Gnazzo V, Acosta H, Lopez SL, Carrasco AE. (2010). Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling. Chem Res Toxicol, 23, 1586–95.
   PubMed Web of Science ®Google Scholar
• Panchin AY. (2013). Toxicity of Roundup-tolerant genetically modified maize is not supported by statistical tests. Food Chem Toxicol, 53, 475.
   PubMed Web of Science ®Google Scholar
• Romano MA, Romano RM, Santos LD, Wisniewski P, Campos DA, de Souza PB, et al. (2012). Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression. Arch Toxicol, 86, 663–73.
   PubMed Web of Science ®Google Scholar
• Romano RM, Romano MA, Bernardi MM, Furtado PV, Oliveira CA. (2010). Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Arch Toxicol, 84, 309–17.
   PubMed Web of Science ®Google Scholar
• Saltmiras D, Remick A, Haas M. (2011). Repeat dietary administration of an organic acid causes salivary gland alterations. Toxicol Lett, 205S, S233.
   Google Scholar
• Saltmiras D, Tobia A. (2012). No evidence of endocrine disruption by glyphosate in Hershberger and Uterotrophic assays (Conference Abstract PS 2198). The Toxicologist (supplement to Toxicological Sciences), 126, 474.
   Google Scholar
• Sanders D, Kamoun S, Williams B, Festing M. (2013). Re: Seralini, G.-E., et al. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem. Toxicol. (2012). Food Chem Toxicol, 53, 450–3.
   PubMed Web of Science ®Google Scholar
• Schmitz P, Harvert H. (2012). Die ökonomische Bedeutung des Wirkstoffes Glyphosat für den Ackerbau in Deutschland [Agro-Economic Analysis of the use of Glyphosate in Germany]. J Kulturpflanzen, 64, 150–62.
   Google Scholar
• Schorsch F. (2013). Serious inadequacies regarding the pathology data presented in the paper by Seralini et al. (2012). Food Chem Toxicol, 53, 465–6.
   PubMed Web of Science ®Google Scholar
• Seralini GE, Clair E, Mesnage R, Gress S, Defarge N, Malatesta M, et al. (2014). Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Environ Sci Eur [Online], 26, 14.
   PubMedGoogle Scholar
• Son WC, Gopinath C. (2004). Early occurrence of spontaneous tumors in CD-1 mice and Sprague-Dawley rats. Toxicol Pathol, 32, 371–4.
   PubMed Web of Science ®Google Scholar
• Sorahan T. (2012). Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study data. Abstract P27-02. Toxicol Lett, 211S, S127.
   Google Scholar
• Syngenta. (1996a). Glyphosate Acid: 1 Year Dietary Toxicity Study in Dogs. Alderley Park, Macclesfield, Cheshire, UK: Central Toxicology Laboratory.
   Google Scholar
• Syngenta. (1996b). Glyphosate Acid: One Year Dietary Toxicity Study in Rats. CTL/P/5143.
   Google Scholar
• Syngenta. (2001). Glyphosate Acid: Two Year Dietary Toxicity and Oncogenicity Study in Rats. Central Toxicology Laboratory, Alderley Park Macclesfield, Cheshire, UK: Syngenta.
   Google Scholar
• Taddesse-Heath L, Chattopadhyay SK, Dillehay DL, Lander MR, Nagashfar Z, Morse HC, III, Hartley JW. (2000). Lymphomas and high-level expression of murine leukemia viruses in CFW mice. J Virol, 74, 6832–7.
   PubMed Web of Science ®Google Scholar
• Tester M. (2013). It does not become the quality of a journal such as Food and Chemical Toxicology to publish such poor work. Food Chem Toxicol, 53, 457.
   PubMed Web of Science ®Google Scholar
• Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, et al. (2010). Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary system. Toxicol Pathol, 38, 5S–81S.
   PubMed Web of Science ®Google Scholar
• Trewavas A. (2013). Science requires the dispassionate presentation of information. Food Chem Toxicol, 53, 449.
   PubMed Web of Science ®Google Scholar
• Tribe D. (2013). My comments about the paper do not adequately describe the serious failures that have occurred in the peer review process at FCT. Food Chem Toxicol, 53, 467–72.
   PubMed Web of Science ®Google Scholar
• US EPA. (1993). Reregistration eligibility decision (RED): glyphosate. United States Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic Substances. Washington, DC, USA.
   Google Scholar
• US EPA. (2012). OCSPP Harmonized Test Guidelines - Series 870 - Health Effects Test Guidelines. Available at: http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series870.htm. Accessed on November 13, 2012.
   Google Scholar
• Webb E, Saltmiras D, Levine S. (2013). Endocrine Disruptor Screening Program (EDSP) Tier 1 In Vitro Assays Indicate Glyphosate Does Not Interact with Estrogen and Androgen Receptor Nor Inhibit Steroidogenesis (Poster abstract P500. American College of Toxicology 33rd Annual Meeting, November 4–7, 2012). Int J Toxicol, 32, 77.
   Web of Science ®Google Scholar
• Weichenthal S, Moase C, Chan P. (2010). A review of pesticide exposure and cancer incidence in the Agricultural Health Study cohort. Environ Health Perspect, 118, 1117–25.
   PubMed Web of Science ®Google Scholar
• WHO/FAO. (2004a). Pesticides residues in food – 2004. Part II Toxicological Evaluations. Joint meeting of the FAO Panel of Experts on pesticide residues in food and the environment and the WHO Core Assessment Group (JMPR). World Health Organization/Food and Agriculture Organization of the United Nations, Rome, Italy. http://www.inchem.org/documents/jmpr/jmpmono/v2004pr01.pdf. Accessed on 20th, January 2015.
   Google Scholar
• WHO/FAO. (2004b). Pesticides residues in food – 2004. 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 (JMPR). World Health Organization/Food and Agriculture Organization of the United Nations, Rome, Italy. http://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/JMPR/Reports_1991-2006/report2004jmpr.pdf. Accessed on 20th, January 2015.
   Google Scholar
• Williams AL, Watson RE, DeSesso JM. (2012). Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis. J Toxicol Environ Health B Crit Rev, 15, 39–96.
   PubMed Web of Science ®Google Scholar
• Williams GM, Kroes R, Munro IC. (2000). Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol, 31, 117–65.
   PubMed Web of Science ®Google Scholar
• Woodside FC, Davis AG. (2013). The Bradford Hill Criteria: The Forgotten Predicate. Thomas Jefferson Law Rev, 35, 103–25.
   Google Scholar