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Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects.

Publication ,  Journal Article
Wade, MG; Foster, WG; Younglai, EV; McMahon, A; Leingartner, K; Yagminas, A; Blakey, D; Fournier, M; Desaulniers, D; Hughes, CL
Published in: Toxicol Sci
May 2002

Human populations throughout the world are exposed daily to low levels of environmental contaminants. The consequences of potential interactions of these compounds to human endocrine, reproductive, and immune function remain unknown. The current study examines the effects of subchronic oral exposure to a complex mixture of ubiquitous persistent environmental contaminants that have been quantified in human reproductive tissues. The dosing solution used in this study contained organochlorines (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], polychlorinated biphenyls [PCBs],p,p'-dichlorodiphenoxydichloroethylene [p,p'-DDE],p,p-dichlorodiphenoxytrichloroethane [p,p'-DDT], dieldrin, endosulfan, methoxychlor, hexachlorobenzene, and other chlorinated benzenes, hexachlorocyclohexane, mirex and heptachlor) as well as metals (lead and cadmium). Each chemical was included in the mixture at the minimum risk level (MRL) or tolerable daily intake (TDI) as determined by the U.S. EPA or ATSDR or, for TCDD, at the no observable effect level (NOEL) used to calculate the TDI. Sexually mature male rats were exposed to this complex mixture at 1, 10, 100, and 1000 times the estimated safe levels daily for 70 days. On day 71, all animals were sacrificed and a variety of physiological systems assessed for toxic effects. Evidence of hepatotoxicity was seen in the significant enlargement of the liver in the 1000x group, reduced serum LDH activity (100x), and increased serum cholesterol and protein levels (both 1000x). Hepatic EROD activities were elevated in animals exposed to10x and above. The mixture caused decreased proliferation of splenic T cells at the highest dose and had a biphasic effect on natural killer cell lytic activity with an initial increase in activity at 1x followed by a decrease to below control levels in response to 1000x. No treatment-related effects were seen on bone marrow micronuclei, daily sperm production, serum LH, FSH, or prolactin levels or weights of most organs of the reproductive tract. The weights of the whole epididymis and of the caput epididymis were significantly decreased at 10x and higher doses, although no effect was seen on cauda epididymal weight. The sperm content of the cauda epididymis was increased at the 1x level but not significantly different from control at higher dose levels. A slight, but significant, increase in the relative numbers of spermatids was seen in the animals from the 1000x group with a trend towards reduced proportion of diploid cells at the same dose. Only minor, nondose related changes were seen in parameters related to condensation of chromatin, as determined by flow cytometry, in epididymal sperm. We conclude that the mixture induced effects on the liver and kidney and on general metabolism at high doses but caused only minor effects on immune function, reproductive hormone levels, or general indices of reproductive function measures. These data suggest that additive or synergistic effects of exposure to contaminants resulting in residue levels representative of contemporary human tissue levels are unlikely to result in adverse effects on immune function or reproductive physiology in male rats.

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Published In

Toxicol Sci

DOI

ISSN

1096-6080

Publication Date

May 2002

Volume

67

Issue

1

Start / End Page

131 / 143

Location

United States

Related Subject Headings

  • Xenobiotics
  • Toxicology
  • Toxicity Tests
  • Reproduction
  • Rats, Sprague-Dawley
  • Rats
  • Microsomes, Liver
  • Micronucleus Tests
  • Metals, Heavy
  • Male
 

Citation

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Wade, M. G., Foster, W. G., Younglai, E. V., McMahon, A., Leingartner, K., Yagminas, A., … Hughes, C. L. (2002). Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects. Toxicol Sci, 67(1), 131–143. https://doi.org/10.1093/toxsci/67.1.131
Wade, Michael G., Warren G. Foster, Edward V. Younglai, Avril McMahon, Karen Leingartner, Al Yagminas, David Blakey, Michel Fournier, Daniel Desaulniers, and Claude L. Hughes. “Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects.Toxicol Sci 67, no. 1 (May 2002): 131–43. https://doi.org/10.1093/toxsci/67.1.131.
Wade MG, Foster WG, Younglai EV, McMahon A, Leingartner K, Yagminas A, et al. Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects. Toxicol Sci. 2002 May;67(1):131–43.
Wade, Michael G., et al. “Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects.Toxicol Sci, vol. 67, no. 1, May 2002, pp. 131–43. Pubmed, doi:10.1093/toxsci/67.1.131.
Wade MG, Foster WG, Younglai EV, McMahon A, Leingartner K, Yagminas A, Blakey D, Fournier M, Desaulniers D, Hughes CL. Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects. Toxicol Sci. 2002 May;67(1):131–143.
Journal cover image

Published In

Toxicol Sci

DOI

ISSN

1096-6080

Publication Date

May 2002

Volume

67

Issue

1

Start / End Page

131 / 143

Location

United States

Related Subject Headings

  • Xenobiotics
  • Toxicology
  • Toxicity Tests
  • Reproduction
  • Rats, Sprague-Dawley
  • Rats
  • Microsomes, Liver
  • Micronucleus Tests
  • Metals, Heavy
  • Male