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ToxSci Advance Access published online on April 19, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj203
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received January 18, 2006
Accepted April 13, 2006

Reproductive and Developmental Toxicology

Three-Generation Evaluation of Dietary para-Nonylphenol in CD® (SD) Rats

R. W. Tyl 1 *, C. B. Myers 1, M. C. Marr 1, N. P. Castillo 1, J. C. Seely 2, C. S. Sloan 1, M. M. Veselica 1, R. L. Joiner 3, J. P. Van Miller 4, and G. S. Simon 5

1 RTI International, Research Triangle Park, NC 27709
2 Experimental Pathology Laboratories, Research Triangle Park, NC 27709
3 General Electric Company, Pittsfield, MA 01201
4 Toxicology/Regulatory Services, Charlottesville, VA 22911
5 Rhodia Inc., Raleigh, NC 27615

* To whom correspondence should be addressed.
R. W. Tyl, E-mail: rwt{at}rti.org


  Abstract

This study evaluated the potential for dietary para-nonylphenol (NP; CAS No. 84852-15-3), to affect parental fertility, and growth and development of 3 offspring generations in CD® (SD) rats, including sperm counts across generations to determine the validity of equivocal reductions observed in the F2 generation by Chapin et al. (1999). Male rat kidney toxicity was also examined based on inconsistent observations in NP-exposed rats at 2000 but not at 200 or 650 ppm in Purina 5002 (Cunny et al., 1997), and at all of these NP concentrations in NIH-07 diet (Chapin et al., 1999). Concentrations were 0, 20, 200, 650, and 2000 ppm NP in Purina 5002 diet and 0 and 650 ppm NP in NIH-07 diet. 17{beta}-estradiol (E2) was used as a positive control at 2.5 ppm in Purina 5002 diet.

There were no NP effects on any reproductive parameters in any generation, including sperm counts. Kidney toxicity (histopathology) occurred at 650 and 2000 ppm with no clear difference for the 2 diets. Ovarian weight was decreased at 2000 ppm NP in all generations, with no effect on reproduction. Dietary E2 at 2.5 ppm caused renal, reproductive, and developmental (lactational and peri-pubertal) toxicity in all generations.

This study confirmed that dietary NP is not a selective reproductive toxicant with a NOAEL of > 2000 ppm (~>150 mg/kg/day), and provided a NOAEL for male rat kidney toxicity of 200 ppm NP (~15 mg/kg/day). This work was supported by the Alkylphenols and Ethoxylates Research Council (APERC), Washington, DC.

Keywords: p-Nonylphenol; 17{beta}-Estradiol; Reproduction; Kidney; CD® (SD) rats; Purina Certified 5002 Diet; NIH-07 Diet.
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R. W. Tyl, C. B. Myers, M. C. Marr, C. S. Sloan, N. P. Castillo, M. M. Veselica, J. C. Seely, S. S. Dimond, J. P. Van Miller, R. S. Shiotsuka, et al.
Two-Generation Reproductive Toxicity Evaluation of Dietary 17{beta}-Estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) Mice
Toxicol. Sci., April 1, 2008; 102(2): 392 - 412.
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