ABSTRACT
Phthalate esters and related compounds Many studies have demonstrated potency differences between various phthalate esters and related compounds. For example, the branched chain ester DEHP (compound IX in Figure 14.1) has been shown to be more potent in producing hepatic peroxisome proliferation in the rat than either diethyl, di-n-hexylphthalate, or di-n-octylphthalate (Moody and Reddy, 1978; Lake et al., 1984b; Mann et al., 1985; Reddy et al., 1986). In a series of 21-day feeding studies, Barber et al. (1987) investigated the effects of DEHP, seven other phthalate esters and DEHA (compound XI in Figure 14.1) on peroxisome numbers and associated enzyme activities in rat liver. These studies demonstrated that branched -chain esters such as DEHP, di-(isodecyl) phthalate (DIDP) and di-(isononyl) phthalate (DINP) were much more potent (Figure 14.4) than n-butylbenzylphthalate (BBP) and three mixtures of phthalate esters (Barber et al., 1987; Hirzy, 1989), namely di-(undecyl) phthalate (DUP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), and di-(heptyl, nonyl, undecyl) phthalate (71 IP). In contrast, in these studies DEHA and, to some extent, di-n-butyl phthalate (DBP) had intermediate potencies for induction of hepatic palmitoyl-CoA oxidation activity (Figure 14.4). While only limited bioassay data are available for DINP, BBP and 711P, the data are consistent, to some degree, with the potency of these compounds and DEHP to produce hepatic peroxisome proliferation in rodent liver (Hirzy, 1989). Differences in potencies for phthalate ester induced hepatic peroxisome proliferation have also been reported in 28-day feeding studies conducted in the rat, where no effect levels for induction of hepatic palmitoyl-CoA oxidation activity by DEHP, DIDP and DBP were reported to be 51.7, 57.0 and 104 mg kg-1 day-1, respectively (Lake et al., 1991).
