Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans

Reviews on the safety of glyphosate and Roundup herbicide that have been co nducted by several regulatory agencies and scientific institutions worldwid e have concluded that there is no indication of any human health concern. N evertheless, questions regarding their safety are periodically raised. This review was undertaken to produce a current and comprehensive safety evalua tion and risk assessment for humans. It includes assessments of glyphosate, its major breakdown product [aminomethylphosphonic acid (AMPA)], its Round up formulations, and the predominant surfactant [polyethoxylated tallow ami ne (POEA)] used in Roundup formulations worldwide, The studies evaluated in this review included those performed for regulatory purposes as well as pu blished research reports. The oral absorption of glyphosate and AMPA is low , and both materials are eliminated essentially unmetabolized. Dermal penet ration studies with Roundup showed very low absorption. Experimental eviden ce 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 mo st, only minimal effects. The genotoxicity data for glyphosate and Roundup were assessed using a weight-of-evidence approach and standard evaluation c riteria. 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 potent ial for glyphosate. Accordingly, it was concluded that glyphosate is noncar cinogenic. Glyphosate, AMPA, and POEA were not teratogenic or developmental ly toxic. There were no effects on fertility or reproductive parameters in two multigeneration reproduction studies with glyphosate, Likewise there we re no adverse effects in reproductive tissues from animals treated with gly phosate, AMPA, or POEA in chronic and/or subchronic studies. Results from s tandard studies with these materials also failed to show any effects indica tive of endocrine modulation. Therefore, it is concluded that the use of Ro undup herbicide does not result in adverse effects on development, reproduc tion, or endocrine systems in humans and other mammals. For purposes of ris k assessment, no-observed-adverse-effect levels (NOAELs) were identified fo r all subchronic, chronic, developmental, and reproduction studies with gly phosate, AMPA, and POEA. Margins-of-exposure for chronic risk were calculat ed for each compound by dividing the lowest applicable NOAEL by worst-case estimates of chronic exposure. Acute risks were assessed by comparison of o ral 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. (C) 2000 Academic Press.