Results of the l5178y mouse lymphoma assay and the balb/3t3 cellin vitro transformation assay for eight phthalate esters

Abstract

Eight phthalate esters, with alcohol chain lengths of 1–11 carbon atoms and with various degrees of branching, were tested in vitro in the L5178Y mouse lymphoma mammalian cell mutation assay and in the Balb/3T3 cell transformation assay. The tests were performed as part of a voluntary testing agreement between the Chemical Manufacturers Association’s Phthalate Esters Panel and the United States Environmental Protection Agency (US EPA). The esters tested were: dimethyl phthalate (DMP), di‐n‐butyl phthalate (DBP), butyl benzyl phthalate (BBP), di‐{n‐hexyl, n‐octyl, n‐decyl} phthalate (610P), di‐isononyl phthalate (DINP), di‐{heptyl, nonyl, undecyl} phthalate (711P), di‐isodecyl phthalate (DIDP) and di‐undecyl phthalate (DUP). Both DMP and DBP were found to produce significant increases in the mutant frequency in the mouse lymphoma assay in the presence but not in the absence of an Aroclor‐induced rat liver activation system (S‐9). Ester 610P gave equivocal results in the mouse lymphoma assay in the presence and absence of rat liver S‐9. There was no indication of mutagenic potential for any of the other test materials in the mouse lymphoma assay, and none of the test materials increased transformation frequency in the Balb/3T3 cell transformation assay. Aldehyde metabolites of the de‐esterified alcohols are postulated to play a role in the positive results for DMP and DBP. Copyright © 2000 John Wiley & Sons, Ltd.

Risk assessment of oral exposure to diisononyl phthalate from children’s products

“…DINP was not mutagenic in Salmonella (McKee et al, 2000;Zeiger et al, 1985) or mouse lymphoma cells (Barber et al, 2000), did not induce unscheduled DNA synthesis in primary rat hepatocytes (Litton Bionetics, 1981), and generally failed to induce phenotypic transformation of BALB/C-3T3 mouse cells either with or without metabolic activation (Barber et al, 2000). In addition, DINP tested negative in various in vitro and in vivo Microbiological Associates, 1981) chromosome damage assays.…”

Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates [Diethyl Phthalate and Di(2-ethylhexyl) Phthalate] as a Case Study

“…Environmental Protection Agency (U.S. EPA) 1993b]. No evidence of other effects in animals at lower NOAELs exists (Api 2001; Barber et al 2000; Gray et al 2000). …”

Comparative Effects of Phthalate Monoesters on Gap Junctional Intercellular Communication and Peroxisome Proliferation in Rodent and Primate Hepatocytes

“…Cancer induction in rats appears to exhibit a threshold for hepatocellular carcinoma (Butala et al, 1996;David et al, 1999). Phthalates have tested negative in most short-term mutagenicity bioassays and thus appear to function through nongenotoxic/epigenetic mechanisms (Barber et al, 2000;Huber et al, 1996;Zeiger et al, 1985;McKee et al, 2000). While the mechanism of liver tumor induction is not clearly understood, our group has recently shown that induction of peroxisomal proliferation in rodent liver by several phthalates along with inhibition of gap junctional intercellular communication correlates with carcinogenic potential .…”