The phthalate syndrome in rodents and humans: Comparing outcomes and exposures

Swan, SH

HERO ID

684205

Reference Type

Journal Article

Subtype

Abstract

Year

2006

Language

English

HERO ID 684205
Material Type Abstract
In Press No
Year 2006
Title The phthalate syndrome in rodents and humans: Comparing outcomes and exposures
Authors Swan, SH
Journal Birth Defects Research, Part A: Clinical and Molecular Teratology
Volume 76
Issue 5
Page Numbers 345
Abstract An extensive body of animal studies has demonstrated that prenatal phthalate exposure, by lowering fetal testicular testosterone, can cause testicular, epididymal, and gubernacular cord agenesis, as well as shortened anogenital distance (AGD). This cluster of abnormalities has been termed the "phthalate syndrome". We present data from the first study to examine AGD and related endpoints in relation to in utero phthalate exposure in humans. Methods: A standardized measure of AGD and some of the genital measurements used to identify the phthalate syndrome in rodents were obtained in boys 2-30 months of age. Alternative methods for adjusting AGD and body weight at examination were compared. Markers of genital development were examined in relation to phthalate metabolite levels in stored prenatal urine samples. These phthalate levels were compared to those measured in a national sample and to those causing phthalate syndrome in rodents. Results: Four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP)] were inversely related to AGD (p-values from 0.012 (MEP) to 0.055 (MBzP). Comparing concentration in the highest to the lowest quartiles, the odds ratio for a shorter-than-predicted AGD ranged from 3.8 to 10.2 (all p-values < 0.05). AGD was more strongly related to a measure of joint exposure to these four phthalate metabolites. Shorter AGD was correlated with a measure of testicular descent and penile volume. The urinary phthalate concentrations associated with shorter AGD were consistent with those that have been measured in one-quarter of the female population of the United States. The median intake estimates associated with reduced AGD are two orders of magnitude below the USEPA reference doses for these chemicals. Discussion: We demonstrated associations between phthalates and genital development that are consistent with the anti-androgenic action of phthalates and the development of the phthalate syndrome previously identified in rodents at higher doses. This study supports the hypothesis that prenatal phthalate exposure can adversely affect reproductive development in male infants and that current regulatory levels may not be adequately protective.
Is Certified Translation No
Dupe Override No
Conference Location Tucson, AZ
Conference Name Annual Meeting of the Teratology Society
Comments Authoring Organization: UNIV OF ROCHESTER
Is Public Yes
Language Text English
Keyword Pregnancy; Animals; Humans; Male; Female; Rodentia; Phthalic Acids/TOXICITY; Prenatal Exposure Delayed Effects/CHEMICALLY INDUCED; Genitalia/ABNORMALITIES/DRUG EFFECTS; NO CAS RN; 88-99-3
Is Qa No