A comparison of the dose-dependent blood burden of di(2-ethylhexyl)
phthalate (
DEHP) and mono(2-ethylhexyl)
phthalate (
MEHP) in pregnant and nonpregnant rats and marmosets is presented. Sprague-Dawley rats and marmosets were treated orally with 30 or 500 mg
DEHP/kg per day, nonpregnant animals on 7 (rats) and 29 (marmosets) consecutive days, pregnant animals on gestation days 14-19 (rats) and 96-124 (marmosets). In addition, rats received a single dose of 1000 mg
DEHP/kg. Blood was collected up to 48 h after dosing. Concentrations of
DEHP and
MEHP in blood were determined by GC/MS. In rats, normalized areas under the concentration-time curves (AUCs) of
DEHP were two orders of magnitude smaller than the normalized AUCs of the first metabolite
MEHP. Metabolism of
MEHP was saturable. Repeated
DEHP treatment and pregnancy had only little influence on the normalized AUC of
MEHP. In marmosets, most of
MEHP concentration-time courses oscillated. Normalized AUCs of
DEHP were at least one order of magnitude smaller than those of
MEHP. In pregnant marmosets, normalized AUCs of
MEHP were similar to those in nonpregnant animals with the exception that at 500 mg
DEHP/kg per day, the normalized AUCs determined on gestation days 103, 117, and 124 were distinctly smaller. The maximum concentrations of
MEHP in blood of marmosets were up to 7.5 times and the normalized AUCs up to 16 times lower than in rats receiving the same daily oral
DEHP dose per kilogram of
body weight. From this toxicokinetic comparison,
DEHP can be expected to be several times less effective in the offspring of marmosets than in that of rats if the blood burden by
MEHP in dams can be regarded as a dose surrogate for the
MEHP burden in their fetuses.