EPA Science Inventory

Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil

Citation:

Johnstone, A., M. Gilbert, C. Aydin, C. Grace, M. Hasegawa, AND C. Gordon. Thermoregulatory deficits in adult long evans rat offspring exposed perinatally to the antithyroidal drug, propylthiouracil. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 39:1-8, (2013).

Description:

Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor. Propylythiouracil (PTU) was used as a prototypical compound because of its well known anti-thyroidal properties. PTU was added to the drinking water of pregnant rats in concentrations of 0, 1, 2, 3, and 10 ppm from GD 6 through PND 21. Adult male offspring had been implanted with radiotransmitters to monitor Tc and motor activity (MA) were monitored undisturbed at an ambient temperature 22 °C for 12 consecutive days. Data were averaged into a single 24 hour period to minimize impact of ultradian and random changes in Tc and MA. All treatment groups showed a distinct temperature rhythm that is circadian by each day. Rats exposed to 10 ppm PTU exhibited a marked deviation in their regulated Tc with a reduction of approximately 0.4 °C below that of controls throughout the daytime period. Rats exposed to 1 ppm also had smaller but significant reductions in Tc. MA was unaffected by PTU. Overall, developmental exposure to moderate doses of an anti-thyroidal drug led to a permanent reduction in Tc of adult offspring that was independent of changes in MA. We advocate that to detect a subtle deficit in homeostasis such as regulation of Tc brought on by perinatal thyroid insult, a procedure such as radiotelemetry is required.

Purpose/Objective:

Developmental exposure to endocrine disrupting toxicants has been shown to alter a variety of physiological processes in mature offspring. Body (core) temperature (Tc) is a tightly regulated homeostatic system but is susceptible to disruptors of the hypothalamic-pituitary-thyroid axis. We hypothesized that thermoregulation would be disrupted in adult offspring exposed perinatally to an HPT disruptor.

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 05/31/2013
Completion Date: 05/31/2013
Record Last Revised: 10/28/2013
Record Created: 07/17/2013
Record Released: 07/17/2013
OMB Category: Other
Record ID: 257811

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

TOXICOLOGY ASSESSMENT DIVISION

NEUROTOXICOLOGY BRANCH