Regular Article
Safety Evaluation and Risk Assessment of the Herbicide Roundup and Its Active Ingredient, Glyphosate, for Humans

https://doi.org/10.1006/rtph.1999.1371Get rights and content

Abstract

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.

References (189)

  • M.B. Lioi et al.

    Genotoxicity and oxidative stress induced by pesticide exposure in bovine lymphocyte cultures in vitro

    Mutat. Res.

    (1998)
  • M.F. Lockett

    Dangerous effects of isoprenaline in myocardial failure

    Lancet

    (1965)
  • M. Moriya et al.

    Further mutagenicity studies on pesticides in bacterial reversion assay systems

    Mutat. Res.

    (1983)
  • R.E. Morrissey et al.

    Evaluation of rodent sperm, vaginal cytology, and reproductive organ weight data from National Toxicology Program 13-week studies

    Fundam. Appl. Toxicol.

    (1988)
  • J.F. Acquavella et al.

    Human ocular effects from self-reported exposures to Roundup herbicides

    Hum. Exp. Toxicol.

    (1999)
  • A. Adam et al.

    The oral and intratracheal toxicities of Roundup and its components to rats

    Vet. Hum. Toxicol.

    (1997)
  • Allin, J. C. 1989, Glyphosate Residues in Wheat Grain and Straw after Preharvest Treatment with Roundup herbicide....
  • Auletta, C. S. 1983a, A Dermal Sensitization Study in Guinea Pigs—Test Material: Glyphosate. Unpublished report,...
  • Auletta, C. S. 1983b, A Dermal Sensitization Study in Guinea Pigs. Unpublished report, Bio/Dynamics, Inc. East...
  • Auletta, C. S. 1985a, Acute Oral Toxicity Study in Rats. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Auletta, C. S. 1985b, Acute Dermal Toxicity Study in Rabbits. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Auletta, C. S. 1985c, Primary Dermal Irritation Study in Rabbits (4-Hour Exposure). Unpublished report, Bio/Dynamics,...
  • Auletta, C. S. 1985d, Eye Irritation Study in Rabbits. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Y. Baba et al.

    Acute toxicity of the herbicide “Roundup” in the rat

    Jpn. J. Toxicol.

    (1989)
  • Bakke, J. P. 1991, Evaluation of the Potential of AMPA to Induce Unscheduled DNA Synthesis in the in Vitro Hepatocyte...
  • Bechtel, C. L. 1987, Acute Toxicity of Roundup Herbicide Administered by Inhalation to Male and Female Sprague–Dawley...
  • M.A. Bender et al.

    Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample

    Mutat. Res.

    (1989)
  • Birch, M. D. 1973, Toxicological Evaluation of Glyphosate. Unpublished report, Younger Laboratories, Inc. St. Louis,...
  • Birch, M. D. 1977, Toxicity Studies on POEA. Unpublished report, Younger Laboratories, Inc. St. Louis,...
  • Blaszcak, D. L. 1987a, Eye Irritation Study in Rabbits. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Blaszcak, D. L. 1987b, Primary Dermal Irritation Study in Rabbits (4-Hour Exposure/Semi-occlusive Covering)....
  • Blaszcak, D. L. 1987c, A Dermal Sensitization Study in Guinea Pigs. Unpublished report, Bio/Dynamics, Inc. East...
  • Blaszcak, D. L. 1987d, Acute Oral Toxicity Study in Rats. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Blaszcak, D. L. 1987e, Acute Dermal Toxicity Study in Rabbits. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Blaszcak, D. L. 1988, Primary Dermal Irritation Study in Rabbits (4-Hour Exposure/Semi-occlusive Covering). Unpublished...
  • Blaszcak, D. L. 1990, Eye Irritation Study in Rabbits. Unpublished report, Bio/Dynamics, Inc. East Millstone,...
  • Bodden, R. M. 1988a, Metabolism Study of Synthetic 13C/14C-Labeled Glyphosate and Aminomethylphosphonic Acid in...
  • Bodden, R. M. 1988b, Metabolism Study of Synthetic 13C/14C-Labeled Glyphosate and Aminomethylphosphonic Acid in Laying...
  • C. Bolognesi et al.

    Genotoxic activity of glyphosate and its technical formulation Roundup

    J. Agric. Food Chem.

    (1997)
  • Branch, D. K. 1981, Irritation of Isopropylamine Salt of Glyphosate to Rats. Unpublished report, Monsanto Environmental...
  • D. Brusick et al.

    Genotoxicity of radiofrequency radiation: DNA/genetox expert panel

    Environ. Mol. Mutagen.

    (1998)
  • California Environmental Protection Agency, Department of Pesticide Regulation, 1996, California Pesticide Illness...
  • C.P. Carpenter et al.

    Mammalian toxicity of 1-naphthyl-N-methylcarbamate (Sevin insecticide)

    J. Agric. Food Chem.

    (1961)
  • CCME, 1996, A Framework for Ecological Risk Assessment: General Guidance. Canadian Council Of Ministers Of The...
  • Centre de Toxicologie du Quebec, 1988, Etude de L'exposition professionnelle des travailleurs forestiers exposes au...
  • S. Chang et al.

    Endoscopy survey of glyphosate-surfactant intoxication

    J. Toxicol. Clin. Toxicol.

    (1995)
  • C. Clements et al.

    Genotoxicity of select herbicides in Rana catesbeiana tadpoles using the alkaline single-cell gel DNA electrophoresis (Comet) assay

    Environ. Mol. Mutagen.

    (1997)
  • Colvin, L. B, and, Miller, J. A. 1973a, Residue and Metabolism—The Dynamics of Accumulation and Depletion of Orally...
  • Colvin, L. B, and, Miller, J. A. 1973b, Residue and Metabolism—The Gross Distribution of N-Phosphonylmethylglycine-14C...
  • Colvin, L. B, Moran, S. J, and, Miller, J. A. 1973, The Metabolism of Aminomethylphosphonic Acid-14C in the Laboratory...
  • Cited by (659)

    View all citing articles on Scopus

    Roundup is a registered trademark of Monsanto.

    2

    To whom correspondence should be addressed. Fax: (905) 542-2900. E-mail: [email protected].

    View full text