title: Di(isononyl) phthalate (DINP) and di(isodecyl) phthalate (DIDP) are not mutagenic.
abstract: Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.
authors.affiliation: ExxonMobil Biomedical Sciences, Inc. 1545 Route 22 East, PO Box 971, Annandale, NJ 08801-0971, USA. rhmckee@fpe.erenj.com
authors.forename: R H
authors.initials: RH
authors.lastname: McKee
authors.forename: R T
authors.initials: RT
authors.lastname: Przygoda
authors.forename: M A
authors.initials: MA
authors.lastname: Chirdon
authors.forename: G
authors.initials: G
authors.lastname: Engelhardt
authors.forename: M
authors.initials: M
authors.lastname: Stanley
mesh_terms: D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D051379:Mice; D009152:Mutagenicity Tests; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012475:Salmonella
chemical_list: D010795:Phthalic Acids; C012125:diisononyl phthalate; C042080:diisodecyl phthalate