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Related Experiment Videos

Thyroid function and thyroid tumors in toxaphene-treated rats

R S Waritz1, M Steinberg, F K Kinoshita

  • 1BioSante International, Inc., Wilmington, Delaware, USA.

Regulatory Toxicology and Pharmacology : RTP
|October 1, 1996
PubMed
Summary
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This study investigated toxaphene's role in rodent thyroid tumors, suggesting a non-genotoxic mechanism potentially relevant for threshold-based regulation. Further research is needed to confirm human relevance.

Area of Science:

  • Toxicology
  • Endocrinology
  • Carcinogenesis

Background:

  • Traditionally, xenobiotic-induced neoplasia is linked to direct DNA damage with no exposure threshold.
  • Recent evidence suggests some rodent neoplasms may have non-genotoxic or non-human-relevant mechanisms.
  • This challenges the no-threshold regulatory approach for certain chemical exposures.

Purpose of the Study:

  • To investigate the potential non-genotoxic origin of toxaphene-induced thyroid tumors in rodents.
  • To determine if toxaphene's effects on thyroid hormones and histology support a threshold-based regulatory approach.

Main Methods:

  • Male rats were administered technical grade toxaphene daily for 28 days.
  • Serum hormone levels (TSH, T3, T4, rT3) and endocrine organ weights were measured.

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  • Thyroid glands were histopathologically examined for neoplastic changes.

    • Main Results:

    • Toxaphene treatment led to significant, time-related increases in serum TSH levels.
    • Thyroid follicular cell hypertrophy and hyperplasia increased, with decreased colloid stores.
    • No significant changes were observed in T3, T4, rT3, or endocrine organ weights.
    • Observed changes suggest increased T3/T4 excretion due to liver cytochrome P450 induction, a mechanism not typically seen in humans.

    Conclusions:

    • The observed thyroid changes in rats are consistent with a non-genotoxic mechanism, likely involving liver enzyme induction.
    • This mechanism for thyroid neoplasia is not known to occur in humans.
    • Findings support the possibility of regulating toxaphene by a threshold approach, rather than a zero-exposure threshold.