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Sulfosulfuron is a low-use rate sulfonylurea herbicide. A review of the toxicity database for sulfosulfuron indicates that the molecule has a low order of acute toxicity. It is not genotoxic and is not a reproductive, developmental, or nervous system toxicant. There were no indications of endocrine disruption in any study performed with the molecule. The only findings considered to be an adverse effect in mammalian laboratory animals following prolonged subchronic or chronic exposure to sulfosulfuron were isolated to the urinary tract. These findings occurred in conjunction with findings of urolith formation following high-level chemical dosing, resulting in epithelial hyperplasia that, in a few cases, progressed to tumor formation. Mode-of-action information supports the conclusion that these tumors result from a non-genotoxic, threshold-based process that is well established and widely considered to be not relevant to humans. Based on its short-term, infrequent application pattern and very low use rate and crop residues, aggregate and cumulative risk assessments indicate that sulfosulfuron has substantial margins of exposure and does not represent a significant risk to human health.

Tomato plants with delayed fruit ripening have been produced by stable insertion of the gene encoding the 1-aminocyclopropane-1-carboxylic acid deaminase (ACCd) protein into the tomato chromosome. Two approaches were used to assess the safety of the ACCd protein for human consumption. Purified Escherichia coli-produced ACCd protein, which is chemically and functionally equivalent to the ACCd protein produced in delayed ripening tomato fruit, was used in these studies. First, the ACCd protein was readily degraded under simulated mammalian digestive conditions. Second, the ACCd protein did not have any deleterious effects when administered to mice by acute gavage at a dosage of up to 602 mg/kg of body weight. This dosage correlates to greater than a 5000- fold safety factor relative to the average daily consumption of tomatoes, assuming that all tomatoes consumed contain the ACCd protein. These results, in conjunction with previously published data, establish that ingestion of tomato fruit expressing the AC...

Animal feeding studies were conducted with rats, broiler chickens, catfish and dairy cows as part of a safety assessment program for a soybean variety genetically modified to tolerate in-season application of glyphosate. These studies were designed to compare the feeding value (wholesomeness) of two lines of glyphosate-tolerant soybeans (GTS) to the feeding value of the parental cultivar from which they were derived. Processed GTS meal was incorporated into the diets at the same concentrations as used commercially; diary cows were fed 10 g/100 g cracked soybeans in the diet, a level that is on the high end of what is normally fed commercially. In a separate study, laboratory rats were fed 5 and 10 g unprocessed soybean meal 100 g diet. The study durations were 4 wk (rats and dairy cows), 6 wk (broilers) and 10 wk (catfish). Growth, feed conversion (rats, catfish, broilers), fillet composition (catfish), and breast muscle and fat pad weights (broilers) were compared for animals fed the parental and GTS lines. Milk production, milk composition, rumen fermentation and nitrogen digestibility were also compared for dairy cows. In all studies, measured variables were similar for animals fed both GTS lines and the parental line, indicating that the feeding value of the two GTS lines is comparable to that of the parental line. These studies support detailed compositional analysis of the GTS seeds, which showed no meaningful differences between the parental and GTS lines in the concentrations of important nutrients and antinutrients. They also confirmed the results of other studies that demonstrated the safety of the introduced protein, a bacterial 5-enolpyruvyl-shikimate-3-phosphate synthase from Agrobacterium sp. strain CP4.

The safety of 5-enolpyruvylshikimate-3-phosphate synthase enzyme derived from Agrobacterium sp. strain CP4 (CP4 EPSPS) was assessed. CP4 EPSPS is the only protein introduced by genetic manipulation that is expressed in glyphosate-tolerant soybeans, which are being developed to provide new weed-control options for farmers. Expression of this protein in plants imparts high levels of glyphosate tolerance. The safety of CP4 EPSPS was ascertained by evaluating both physical and functional characteristics. CP4 EPSPS degrades readily in simulated gastric and intestinal fluids, suggesting that this protein will be degraded in the mammalian digestive tract upon ingestion as a component of food or feed. There were no deleterious effects due to the acute administration of CP4 EPSPS to mice by gavage at a high dosage of 572 mg/kg body wt, which exceeds 1000-fold the anticipated consumption level of food products potentially containing CP4 EPSPS protein. CP4 EPSPS does not pose any important allergen concerns because this protein does not possess characteristics typical of allergenic proteins. These data, in combination with seed compositional analysis and animal feeding studies, support the conclusion that glyphosate-tolerant soybeans are as safe and nutritious as traditional soybeans currently being marketed.

Two approaches were used to assess the safety of the NPTII protein for human consumption using purified E. coli produced NPTII protein that was shown to be chemically and functionally equivalent to the NPTII protein produced in genetically engineered cotton seed, potato tubers and tomato fruit. The NPTII protein was shown, as expected, to degrade rapidly under simulated mammalian digestive conditions. An acute mouse gavage study confirmed that the NPTII protein caused no deleterious effects when administered by gavage at a cumulative target dosage of up to 5000 mg/kg of body weight. This dosage correlates to at least a million fold safety factor relative to the average daily consumption of potato or tomato, assuming all the potatoes or tomatoes consumed contained the NPTII protein. These results, along with previously published information, confirm that ingestion of genetically engineered plants expressing the NPTII protein poses no safety concerns.

Large-scale longitudinal toxicologic animal studies necessarily generate a considerable volume of numerical data points, though only a relatively small number of these data may be variations of interest to the investigator. This computer-based method detects these anomalies of interest by the use of predetermined criteria which create an individual element “window” to which each data point is compared. The anomalies thus detected are presented in various formats which assist the investigator in drawing scientific conclusions. The tedious manual task of screening the original data is eliminated, the accuracy is improved and professional time is conserved. The methodology of setting the windows is described, and typical sample outputs are presented.