Effects of Mono‐n‐butyl Phthalate on the Development of Rat Embryos: In vivo and in vitro Observations

Abstract

The present study was conducted to further characterize the embryotoxic effects mono-n-butyl phthalate, a major metabolite of the plasticizer di-n-butyl phthalate, and evaluate its role in the developmental toxicity of di-n-butyl phthalate. The embryotoxic effects of mono-n-butyl phthalate were compared to those of the parent compound di-n-butyl phthalate after a single oral administration of 1.8, 3.6, 5.4, or 7.2 mmol/kg di-n-butyl phthalate or mono-n-butyl phthalate to Sprague-Dawley rats on gestational day 10 (Day 10). Embryos were evaluated for growth and development on Day 12. Both chemicals induced concentration-dependent developmental toxicity (i.e. decreased growth and malformations) which became apparent at 3.6 mmol/kg. Di-n-butyl phthalate and mono-n-butyl phthalate were approximately equally potent and produced qualitatively similar dysmorphogenic effects. Macroscopically, the most common malformations involved the prosencephalon, the optic system, and the mandibular and maxillary processes. In addition, the embryotoxic potential of mono-n-butyl phthalate was evaluated in vitro using the rat whole embryo culture system. Day 10 embryos were cultured for 48 hr in the presence of 0.5 to 5 mM mono-n-butyl phthalate and were then evaluated as the embryos grown in utero. Mono-n-butyl phthalate was a potent direct acting embryotoxicant, causing concentration-related growth retardation and dysmorphogenesis. The spectrum of morphological defects observed in mono-n-butyl phthalate-exposed embryos in vitro was comparable to those seen in vivo in the embryos at the same developmental stage after maternal administration of di-n-butyl phthalate or mono-n-butyl phthalate. These data provide additional evidence in support of the hypothesis that mono-n-butyl phthalate may be the active species for the developmental toxicity of ingested di-n-butyl phthalate in rats.

Polyamines protect rat embryo in vitro from high glucose‐induced developmental delay and dysmorphogenesis

“…Culture was realized as described by New (1978). Briefly, embryos were placed in a sterile bottle, with 1.0 mL/embryo of the respective media, previously gassed 3-5 min with 5% O 2 /5% CO 2 /90% N 2 (Salleinfait et al, 2001). The culture bottles were rolled on a 30-rpm rotator wheel in a 371C incubator.…”

Determination of Phthalate Esters in the Children's Products Using Ultrasonic Extraction and Gas Chromatography

“…As the infant's reproductive system. Endocrine system and Immune System are not yet fully developed, PAEs may affect the fetus and infant hormone secretion, causing hormone imbalance [4][5][6] . It may lead to children sexual precocity and impact on the reproductive system.…”

Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure

“…It may enter human bodies through many ways, such as food, air and medical treatment. Once in the body, DBP is quickly metabolized to monobutyl phthalate (MBP), which is responsible for the induction of the developmental toxic eff ects of DBP (Saillenfait et al, 2001). In the US National Health and Nutrition Examination Surveys (NHANES) III (1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994) survey, MBP (95th percentile 294 ppb, median 41.0 ppb) as well as other metabolites of phthalate were detected in almost 300 urine specimens collected from adults (Blount et al, 2000), refl ecting exposure to the parent compound DBP and other phthalates.…”