title: Toxicological assessment of refined naphthenic acids in a repeated dose/developmental toxicity screening test.
abstract: Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic.
authors.affiliation: ExxonMobil Biomedical Sciences, Inc, 1545 US Highway 22 East, Annandale, NJ 08801, USA. Email: richard.h.mckee@exxonmobil.com.
authors.forename: Richard H
authors.initials: RH
authors.lastname: McKee
authors.forename: Colin M
authors.initials: CM
authors.lastname: North
authors.forename: Paula
authors.initials: P
authors.lastname: Podhasky
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Charlap
authors.forename: Adam
authors.initials: A
authors.lastname: Kuhl
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D012475:Salmonella / Q000187:drug effects; D018675:Toxicity Tests
chemical_list: D002264:Carboxylic Acids; D009153:Mutagens; C046170:naphthenic acid
keywords: OECD 422; chemical abstract services registry number 1338-24-5; naphthenic acids; toxicity assessment