The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Mono(2-ethylhexyl)phthalate and 2-ethylhexanol are metabolites of di(2-ethylhexyl)phthalate, a widely used phthalate ester plasticizer. In order to determine their contribution to DEHP's developmental toxicity, MEHP (NTP, 1990) and 2-EH (this study) were evaluated under conditions comparable to those in a previous study of DEHP (Tyl et al., 1988).
Microencapsulated 2-EH (0%, 0.009%, 0.03%, or 0.09% in feed) was provided on gestational days (gd) 0 to 17 ad libitum to timed-mated CD-1 mice (28/group). At sacrifice (gd 17),the number of ovarian corpora lutea and uterine implantation sites, including resorptions, and dead or live fetuses, were recorded. Live and dead fetuses were weighed. Live fetuses were sexed and examined for external, visceral and skeletal malformations and variations.
No dams died, delivered early or were removed from study. Pregnancy rate was high (93-96%) and equivalent across all groups. One litter at 0% was fully resorbed; all other pregnant animals had live litters at scheduled necropsy. The numbers of live litters evaluated were 27 at 0.009 and 0.03% and 26 at 0 and 0.09% 2-EH. There was no treatment-related maternal toxicity observed in this study. Maternal body weights, weight gains (absolute or corrected for gravid uterine weight), gravid uterine weight and liver weight (absolute or relative to body weight) were unaffected. Food consumption (g/kg/day and g/day) was significantly increased for gd 0-3 at 0.09% and unaffected for all other time points evaluated. The calculated consumption of 2-EH, based on gestational food consumption was 0 (0 mmol/kg), 17 (0.13 mmol/kg), 59 (0.46 mmol/kg) and 191 mg/kg/day (1.49 mmol/kg), for the 0, 0.009, 0.03 and 0.090% groups, respectively.
There were no effects of exposure to dietary 2-EH on any gestational parameters. The number of corpora lutea, uterine implantation sites (live, dead, resorbed), pre- and postimplantation loss, sex ratio (%, males) and live fetal body weight per litter (all fetuses or separately by sex) were all equivalent across all groups. There were also no treatment-related changes in the incidence of individual, external, visceral, skeletal or total malformations or variations.
In conclusion, there were no maternal or developmental toxic effects of 2-EH dietary exposure throughout gestation at any concentration tested, in contrast to the qualitatively similar maternal and developmental toxicity previously reported for DEHP (Tyl et al., 1988) and MEHP (NTP, 1990) at approximately equimolar doses administered under comparable experimental conditions. The present study therefore indicates that 2-EH plays essentially no role in the expression of DEHP-induced maternal and developmental toxicity.