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668088 
Journal Article 
Comparative embryotoxicity of di-n-butyl phthalate and its main metabolite mono-n-butyl phthalate at midgestation 
Langonne, I; Saillenfait, AM; Payan, JP 
1998 
1 
Teratology
ISSN: 0040-3709
EISSN: 1096-9926 
DART/TER/98001125 
58 
1 
22A 
English 
Di-n-butyl phthalate (DBP), an extensively used plasticizer, is a well known reproductive and developmental toxicant in rodents. Evidence has been presented to suggest that its metabolite mono-n-butyl phthalate (MBP) may contribute to its embryotoxic effects. In this study, the embryotoxic profiles of DBP and MBP were compared at midgestation. Pregnant Sprague-Dawley rats were given a single oral dose of 1.8, 3.6, 5.4, or 7.2 mmol DBP or MBP/kg on Gestational Day (GD) 10. The embryos were examined for growth and development on GD 12, a window for observing the origin of the lethality previously reported at term after DBP administration on GD 10 (J. Appl. Toxicol., 1997, 17, 223-229). No increase in embryo lethality was observed within 48 hr after administration of DBP or MBP at doses up to 7.2 mmol/kg. Both DBP and MBP produced growth retardation and dysmorphogenesis in a dose-dependent manner. DBP and MBP were essentially without effects at 1.8 mmol/kg. Adverse effects appeared at 3.6 mmol DBP or MBP/kg. At 5.4 mmol DBP or MBP/kg, all the parameters of growth and development assessed (i.e. crown-rump length, head lengths, and number of somite pairs) were reduced, and 80-88% of the embryos were malformed. The spectrum of malformations observed with MBP closely resembled that produced by the parent compound. The commonest morphological alterations were those of the anterior part of the head, and involved the prosencephalon, the optic and otic systems, and the mandibular arches. In addition, maternal plasma was analyzed by HPLC for metabolic species after administration of 5.4 mmol (14C)DBP/kg. MBP accounted for most of the DBP-derived 14C, whereas DBP was barely detectable. These results provide strong evidence that DBP-induced embryotoxic effects are mediated through its main metabolite MBP. 
Pregnancy; Rats; Animal; Female; Comparative study; Sprague-Dawley; Dibutyl Phthalate TOXICITY; Dibutyl Phthalate METABOLISM; Dose-Response Relationship; Drug; Phthalic Acids TOXICITY; Abnormalities; Drug-Induced; 84-74-2; 131-70-4; No cas rn