Acute and 28-day repeated dose toxicology studies in mice with aryloxyalkanoate dioxygenase (AAD-1) protein expressed in 2,4-D tolerant DAS-40278-9 maize

• Published in: Regulatory toxicology and pharmacology Vol. 62; no. 2; pp. 363 - 370
• Main Authors: Stagg, Nicola J., Thomas, Johnson, Herman, Rod A., Juberg, Daland R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2012
• Subjects: 2,4-Dichlorophenoxyacetic Acid - toxicity; 28-Day toxicity study; Acute toxicology; Animals; Biotechnology; Corn; Dioxygenases - genetics; Dose-Response Relationship, Drug; Female; Herbicides - toxicity; Maize; Male; Mice; Plants, Genetically Modified - genetics; Safety; Toxicity Tests, Acute; Transgenic crop; Zea mays - genetics; Acute toxicology; Biotechnology; Transgenic crop; Corn; 28-Day toxicity study; Mice; Maize; Safety
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2011.10.018

► We evaluate the mammalian toxicology of a transgenic protein, AAD-1. ► AAD-1 provides herbicide tolerance in genetically modified corn. ► No toxicity was observed in mice after acute or 28-days with AAD-1. ► We conclude AAD-1 corn represents a negligible risk to human health. DAS-40278-9 maize (corn) plants have been genetically modified by the insertion of the aad-1 gene (aryloxyalkanoate dioxygenase), which confers tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) acetyl coenzyme A carboxylase (ACCase) inhibitors (“fop” herbicides) to enable the effective use of these herbicides on maize. The aad-1 gene, derived from Sphingobium herbicidovorans, encodes the aryloxyalkanoate dioxygenase (AAD-1) enzyme. As part of the safety assessment of the AAD-1 protein expressed in maize, acute and repeated dose mammalian toxicology studies were conducted. AAD-1 protein (heterologously produced) was orally administered to mice at a dose of 2000mg/kg, and no acute lethality or adverse effects were observed. Similarly, no adverse effects were observed in mice in a 28-day repeated-dose dietary toxicity study that incorporated the AAD-1 protein into diets at concentrations up to 1000-fold greater than the highest estimate of human exposure to maize. These results support the conclusion that the AAD-1 protein, as expressed in biotechnology derived DAS-40278-9 maize, represents a negligible risk to human health.