Maternal and offspring toxicity but few sexually dimorphic behavioral alterations result from nonylphenol exposure.
Nonylphenol ethoxylates are used in the production of surfactants and are found in numerous manufactured substances. para-Nonylphenol (NP) is a suspected endocrine disruptor, exhibiting estrogen-like activity and might cause alterations with developmental exposure. To evaluate such effects, pregnant Sprague-Dawley rats consumed diets containing 0 (n = 11), 25 (n = 10), 500 (n = 10), or 2,000 (n = 9) ppm NP beginning on gestational day (GD) 7. At postnatal day (PND) 21, offspring continued on the same maternal diets until PND 77 and were evaluated for behavioral alterations (open-field activity at PNDs 22-24, 43-45, 64-66, play behavior at PND 35, running wheel activity at PND 63-77, flavored solution intake at PND 69-75). During pregnancy and lactation, dams in the 25-, 500-, and 2,000-ppm groups consumed 9 to 25% less food, which was associated with a 17% less weight gain during GDs 1 to 21 in dams of the 2,000-ppm group, although this effect was not statistically significant. Gestation duration, birth weight, sex ratio of live pups, and number of live or dead pups per litter did not differ between treatment groups. Offspring body weight and food consumption were decreased in the 2, 000-ppm group beginning at PND 28; however, an effect of feed aversion could not be eliminated. Behavioral assessments of offspring indicated no consistent NP-related effects in open-field activity at PNDs 22-24, 43-45, and 65-67 nor in running wheel activity at PNDs 63-75. Play behavior at PND 35 and intake of a 0.3% saccharin-flavored solution at PNDs 69-71 did not differ with respect to treatment groups. However, intake of a 3% sodium-flavored solution at PNDs 73-75 was significantly increased in offspring of the 2,000-ppm group and intake of regular water during this same time was also significantly increased. These results indicate that developmental NP treatment results in maternal and offspring toxicity as evidenced by decreased food intake and weight gain. However, behavioral alterations were evident only in increased intake of a sodium solution.
Ferguson
S A
SA
Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
Flynn
K M
KM
Delclos
K B
KB
Newbold
R R
RR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D010636:Phenols; C025256:nonylphenol