title: 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.
abstract: 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.
authors.affiliation: Dow AgroSciences, LLC, Indianapolis, IN 46268, USA. njstagg@dow.com
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Stagg
authors.forename: Johnson
authors.initials: J
authors.lastname: Thomas
authors.forename: Rod A
authors.initials: RA
authors.lastname: Herman
authors.forename: Daland R
authors.initials: DR
authors.lastname: Juberg
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D049308:Dioxygenases / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D051379:Mice; D030821:Plants, Genetically Modified / Q000235:genetics*; D023382:Toxicity Tests, Acute; D003313:Zea mays / Q000235:genetics*
chemical_list: D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid; D049308:Dioxygenases