US EPA

684205 

Journal Article 

Abstract 

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

Swan, SH 

2006 

Yes 

Birth Defects Research, Part A: Clinical and Molecular Teratology
ISSN: 1542-0752
EISSN: 1542-0760 

DART/TER/6001093 

76 

5 

345 

English 

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. 

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 

Annual Meeting of the Teratology Society 

Tucson, AZ