Toxicology and human health risk assessment of polyethoxylated tallow amine surfactant used in glyphosate formulations.

Roundup® branded herbicides contain glyphosate, a surfactant system and water. One of the surfactants used is polyethoxylated tallow amine (POE-T). A toxicology dataset has been developed to derive the most representative points of departure for human health risk assessments. Concentrated POE-T was very irritating to skin, corrosive to eyes, and sensitizing to skin. The irritation and sensitization potential of POE-T diminishes significantly upon dilution with water. Repeated dosing of rats with POE-T produced gastrointestinal effects but no systemic effect on organ systems. POE-T was not genotoxic and had no effect on embryo-fetal development or reproduction. The occupational risk assessment of POE- T for the agricultural use of glyphosate products has demonstrated that margins of exposure (MOEs) are 2517 and 100,000 for maximum and geometric mean dermal exposures, respectively. In the food risk assessment for relevant agricultural uses, the range of MOEs for consumption of foods from plant and animal origin were 330 to 2909. MOEs ≥100 are generally considered to be of no toxicological concern. Based on the results of the occupational and food risk assessments, it is concluded that there are no significant human health issues associated with the use of POE-T as a surfactant in glyphosate products.

Improving insect control protein activity for GM crops: A case study demonstrating that increased target insect potency can be achieved without impacting mammalian safety.

Many insect-protected crops express insecticidal crystal (Cry) proteins derived from the soil bacterium Bacillus thuringiensis (Bt), including both naturally-occurring Cry proteins and chimeric Cry proteins created through biotechnology. The Cry51Aa2 protein is a naturally-occurring Cry protein that was modified to increase its potency and expand its insect activity spectrum through amino acid sequence changes. The improved Cry51Aa2 variant, Cry51Aa2.834_16, and other developmental variants belong to the ETX_MTX2 family of proteins but share a low level of sequence similarity to other members of this family. This similarity is largely localized to the pore-forming and oligomerization protein domains, while sequence divergence is observed within the head domain that confers receptor binding specificity. The intact Cry51Aa2.834_16 protein was heat labile at temperatures ≥55 °C, and was rapidly degraded after exposure to the gastrointestinal protease pepsin. No acute oral toxicity was observed in mice for three protein variants of Cry51Aa2, including Cry51Aa2.834_16, at doses exceeding 1000 mg/kg body weight. The weight-of-evidence therefore supports the conclusion of safety for Cry51Aa2.834_16 and demonstrates that amino acid sequence modifications can be used to substantially increase insecticidal activity of a protein without an increased hazard to mammals.

Genotoxic potential of glyphosate formulations: mode-of-action investigations.

A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

An analysis of glyphosate data from the California Environmental Protection Agency Pesticide Illness Surveillance Program.

Glyphosate is among the pesticides most frequently reported to the California EPA Pesticide Illness Surveillance Program. We analyzed glyphosate-related calls to the Pesticide Illness Surveillance Program in order to assess the number of reports involving systemic symptoms and to better understand the nature and severity of reported cases. Data on glyphosate and other pesticides are available for the years 1982-1997 including: type of exposure (agricultural/other); target organ(s) affected (skin/eye/respiratory/systemic); exposure(s); an assessment of causal relationship (possible, probable, or definite); and limited medical text. Of 815 total glyphosate calls, most involved topical irritation of the eye (n = 399), skin (n = 250), upper airway (n = 7), or combinations of these sites (n = 32) without systemic symptoms. Of the 187 systemic cases, only 22 had symptoms recorded as probably or definitely related to glyphosate exposure alone. The reported symptoms were not severe, expected to be limited in duration, and frequently inconsistent with the route of exposure and/or previous experience with glyphosate. We conclude that call volume is not a reliable indicator of the actual incidence or severity of glyphosate-related incidents in California.