title: Derived Reference Doses (RfDs) for the environmental degradates of the herbicides alachlor and acetochlor: results of an independent expert panel deliberation.
abstract: An independent peer expert panel was convened under the auspices of the Alliance for Risk Assessment (ARA) to review toxicology data and derive oral Reference Doses (RfDs) for four environmental degradates of the acetanilide herbicides, alachlor and acetochlor. The degradates included in this evaluation were (1) alachlor tertiary-ethanesulfonic acid (ESA), (2) alachlor tertiary-oxanilic acid (OXA), (3) acetochlor ESA, and (4) acetochlor OXA. Each degradate was judged to have sufficient data for developing low to medium confidence RfD, with use of an additional uncertainty factor (UF) to cover data gaps. Body weight decreases were identified as the most sensitive treatment-related adverse effect for RfD development. A composite UF of 1000 (10 for human variability in sensitivity, 10 for interspecies differences in sensitivity, and 10 for subchronic to chronic and database deficiency combined; i.e., 10(A)x10(H)x10(S&D)) for each degradate was considered reasonable, while noting that an argument could be made for an UF of 3000 (10(A)x10(H)x30(S&D)). Based on the available data, an oral RfD of 0.2 mg/kg-day is recommended for both acetochlor ESA and acetochlor OXA and an oral RfD of 0.8 mg/kg-day is recommended for both alachlor ESA and alachlor OXA.
authors.affiliation: Toxicology Excellence for Risk Assessment, Cincinnati, OH 45211, USA. gadagbui@tera.org
authors.forename: Bernard
authors.initials: B
authors.lastname: Gadagbui
authors.forename: Andrew
authors.initials: A
authors.lastname: Maier
authors.forename: Michael
authors.initials: M
authors.lastname: Dourson
authors.forename: Ann
authors.initials: A
authors.lastname: Parker
authors.forename: Alison
authors.initials: A
authors.lastname: Willis
authors.forename: John P
authors.initials: JP
authors.lastname: Christopher
authors.forename: Lebelle
authors.initials: L
authors.lastname: Hicks
authors.forename: Santhini
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roberts
mesh_terms: D000081:Acetamides / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D052918:Environmental Restoration and Remediation; D006540:Herbicides / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008962:Models, Theoretical; D019055:No-Observed-Adverse-Effect Level; D012016:Reference Values; D018570:Risk Assessment; D014052:Toluidines / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods / Q000706:statistics & numerical data; D014481:United States
chemical_list: D000081:Acetamides; D004785:Environmental Pollutants; D006540:Herbicides; D014052:Toluidines; C000188:alachlor; C043377:acetochlor