Toxicological Sciences, Vol 52, 80-91, Copyright © 1999 by Society of Toxicology
RE Chapin, J Delaney, Y Wang, L Lanning, B Davis, B Collins, N Mintz and G Wolfe
The alkylphenol breakdown products of alkylphenol ethoxylates have been
shown in in vitro studies to be weakly estrogenic, but few in vivo data
address this issue in mammals. Because estrogens have been found to be most
potent during developmental/perinatal exposures, this study maximized
developmental exposure to nonylphenol (NP) by treating 3.5 generations of
Sprague-Dawley rats to NP in diet at 200, 650, and 2000 ppm to determine
the range and severity of any toxicity. Dose rate was higher for younger
rats; calculated dose ranges were 9-35, 30-100, and 100-350 mg/kg/d for the
low (200NP), middle (650NP), and high (2000NP) dose groups, respectively.
There were adult (F0, F1, F2) and postnatal day (pnd) 21 (F1, F2, F3)
necropsies; the oldest F3 rats were killed on pnd 55-58. Body weight gain
was reduced by 8-10% in the 650NP and 2000NP groups. Vaginal opening was
accelerated by approximately 2 days (650NP) and approximately 6 days
(2000NP) in F1, F2, and F3 generations. Uterine weights at pnd 21 were
increased in 650NP (14%) and 2000NP (50%) F1 females, but not in other
generations. Testis descent, anogenital distance, and preputial separation
were not consistently changed. No consistent changes were seen in pup
number, weight or viability, litter indices, or other functional
reproductive measures. Relative ovary weight in F2 adults was decreased at
650NP and 2000NP by 12%; relative ovary was unchanged in other generations.
Follicle counts were unchanged in F2 adults. Sperm indices, including CASA
measures, were unchanged in F0 and F1 males. In F2 rats, epididymal sperm
density was reduced by 8% and 13% at 650NP and 2000NP, respectively.
Testicular spermatid count was reduced by 13% in 2000NP F2 males; testis
and epididymis weights were unchanged. Erosion of gastric and duodenal
mucosa was monitored grossly and microscopically, and never found. Kidney
weights were increased in 650NP and 2000NP males, and renal medullary
tubular dilatation and cyst formation were noted in all generations of
males, and often at the lowest dose tested. These data show that NP had
limited effects on the reproductive system in the presence of measurable
nephrotoxicity. The F2 sperm effects are either statistical/biological
"noise," or imply heretofore unknown pharmacokinetics or toxicodynamics.
These sperm data should be interpreted cautiously until the findings are
repeated.
ARTICLES
The effects of 4-nonylphenol in rats: a multigeneration reproduction study
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chapin@niehs.nih.gov
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. McClusky, C de Jager, and M. Bornman Stage-Related Increase in the Proportion of Apoptotic Germ Cells and Altered Frequencies of Stages in the Spermatogenic Cycle Following Gestational, Lactational, and Direct Exposure of Male Rats to p-Nonylphenol Toxicol. Sci., January 1, 2007; 95(1): 249 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-K. Kim, B.-K. Kim, J.-H. Shim, J.-E. Gil, Y.-D. Yoon, and J.-H. Kim Nonylphenol and Octylphenol-Induced Apoptosis in Human Embryonic Stem Cells Is Related to Fas-Fas Ligand Pathway Toxicol. Sci., December 1, 2006; 94(2): 310 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Tyl, C. B. Myers, M. C. Marr, N. P. Castillo, J. C. Seely, C. S. Sloan, M. M. Veselica, R. L. Joiner, J. P. Van Miller, and G. S. Simon Three-Generation Evaluation of Dietary para-Nonylphenol in CD (Sprague-Dawley) Rats Toxicol. Sci., July 1, 2006; 92(1): 295 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cooper, J. R. Latendresse, D. R. Doerge, N. C. Twaddle, X. Fu, and K. B. Delclos Dietary Modulation of p-Nonylphenol-Induced Polycystic Kidneys in Male Sprague-Dawley Rats Toxicol. Sci., June 1, 2006; 91(2): 631 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Masuno, S. Okamoto, J. Iwanami, K. Honda, T. Shiosaka, T. Kidani, K. Sakayama, and H. Yamamoto Effect of 4-Nonylphenol on Cell Proliferation and Adipocyte Formation in Cultures of Fully Differentiated 3T3-L1 Cells Toxicol. Sci., October 1, 2003; 75(2): 314 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Lee, S. Chattopadhyay, E.-Y. Gong, R. S. Ahn, and K. Lee Antiandrogenic Effects of Bisphenol A and Nonylphenol on the Function of Androgen Receptor Toxicol. Sci., September 1, 2003; 75(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Daston, J. C. Cook, and R. J. Kavlock Uncertainties for Endocrine Disrupters: Our View on Progress Toxicol. Sci., August 1, 2003; 74(2): 245 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Latendresse, R. R. Newbold, C. C. Weis, and K. B. Delclos Polycystic Kidney Disease Induced in F1 Sprague-Dawley Rats Fed para-Nonylphenol in a Soy-Free, Casein-Containing Diet Toxicol. Sci., July 1, 2001; 62(1): 140 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Davis, G. Travlos, and T. McShane Reproductive Endocrinology and Toxicological Pathology over the Life Span of the Female Rodent Toxicol Pathol, January 1, 2001; 29(1): 77 - 83. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Atanassova, C. McKinnell, K. J. Turner, M. Walker, J. S. Fisher, M. Morley, M. R. Millar, N. P. Groome, and R. M. Sharpe Comparative Effects of Neonatal Exposure of Male Rats to Potent and Weak (Environmental) Estrogens on Spermatogenesis at Puberty and the Relationship to Adult Testis Size and Fertility: Evidence for Stimulatory Effects of Low Estrogen Levels Endocrinology, October 1, 2000; 141(10): 3898 - 3907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Odum and J. Ashby Neonatal Exposure of Male Rats to Nonylphenol Has No Effect on the Reproductive Tract Toxicol. Sci., August 1, 2000; 56(2): 400 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Nagao, Y Saito, K Usumi, M Nakagomi, S Yoshimura, and H Ono Disruption of the reproductive system and reproductive performance by administration of nonyiphenol to newborn rats Human and Experimental Toxicology, May 1, 2000; 19(5): 284 - 296. [Abstract] [PDF]
|
|
|
|
|
|
R. M. Blair, H. Fang, W. S. Branham, B. S. Hass, S. L. Dial, C. L. Moland, W. Tong, L. Shi, R. Perkins, and D. M. Sheehan The Estrogen Receptor Relative Binding Affinities of 188 Natural and Xenochemicals: Structural Diversity of Ligands Toxicol. Sci., March 1, 2000; 54(1): 138 - 153. [Abstract] [Full Text] [PDF]
|
|