Fetotoxic Effects of Mono-2-Ethylhexyl Phthalate (MEHP) in Mice

Abstract

Mono(2-ethylhexyl) phthalate (MEHP), one of the main metabolites of di(2-ethylhexyl) phthalate (DEHP), exerted embryo/fetotoxic effects similar to those of DEHP at lower doses. Oral administration of MEHP (1 mL/kg) to the mice of 8 days gestation resulted in less than 32% of live fetuses, all of which were deformed.When DEHP (10 mL/kg) was given to the pregnant mice of 8 days gestation, approximately 0.03% and 0.003% of the administered dose was found in fetuses as DEHP and MEHP, respectively, after 12 hr.The presence of the MEHP in fetuses is probably due to the transplacental crossing of the MEHP formed in the maternal body, since the fetuses of mice up to day 9 of pregnancy showed no hydrolytic activity of DEHP to MEHP. Crossing of MEHP through the placenta was proven by an experiment in which MEHP was administered in pregnant mice.A single injection of MEHP (25 or 50 mg/kg), but not DEHP (500 mg/kg) into pregnant mice, induced a significantly high incidence of somatic mutations in the coat hair of offspring of mice (KYG, 9 x PW, d; C57BL/6Crj, 9 x PW, 6). All these data suggest that MEHP could be responsible for the embryotoxic/ fetotoxic effects observed with DEHP.

Exposure to Di(2-ethylhexyl)phthalate in Humans during Pregnancy

“…To date, little information exists concerning transplacental crossing of these plasticizers in animal models [18,19], but DEHP-induced testicular damage and antiandrogenic action in prenatally exposed animals have been reported previously [6][7][8][9][10][11][12]. On the other hand, there is no indication concerning the distribution of phthalates in the maternal-placental-fetal compartments and DEHP/ MEHP-related toxicity of fetal exposure in humans.…”

Transfusion‐related exposure to the plasticizer di(2‐ethylhexyl)phthalate in patients receiving plateletpheresis concentrates

“…Concerns arise, however, in special patient groups, like neonates, children, pregnant women, or patients with impaired liver function. DEHP can cross the placenta, 33 exposing the fetus secondarily to maternal exposures. Newborns and infants can receive the highest doses of DEHP from other medical interventions like extracorporeal membrane oxygenation or respiratory therapy 34 .…”

Mechanisms of phthalate ester toxicity in the female reproductive system.

“…These effects are dose dependent, with a maximal no effect level of DEHP on mouse fetuses of 70 mg/kg/day. Tomita et al (1986) showed that effects of DEHP in mice depend on dose and timing of exposure. Exposure on gestational days 7 and 8 led to a high incidence of death and malformations, but exposure on other days had fewer effects (Tomita et al 1986).…”

“…Tomita et al (1986) showed that effects of DEHP in mice depend on dose and timing of exposure. Exposure on gestational days 7 and 8 led to a high incidence of death and malformations, but exposure on other days had fewer effects (Tomita et al 1986). In utero exposure to DEHP causes embryotoxic and teratogenic effects in mice and rats (Shiota and Nishimura 1982;Tyl et al 1988).…”