Low-dose effects of ammonium perchlorate on the hypothalamic-pituitary-thyroid axis of adult male rats pretreated with PCB126.
The objective of this research was to characterize the disturbances in the hypothalamic-pituitary-thyroid (HPT) axis resulting from exposure to a binary mixture, 3,3',4,4',5-pentachlorobiphenyl (PCB126) and perchlorate (ClO(4)(-)), known to cause hypothyroidism by different modes of action. Two studies were conducted to determine the HPT axis effects of ClO(4)(-) on adult male Sprague-Dawley rats pretreated with PCB126. In dosing study I, rats were administered a single oral dose of PCB126 (0, 7.5, or 75 microg/kg) on day 0 and 9 days later ClO(4)(-) (0, 0.01, 0.1, or 1 mg/kg day) was added to the drinking water until euthanasia on day 22. Significant dose-dependent trends were found for all thyroid function indices measured following ClO(4)(-) in drinking water for 14 days. Seventy-five micrograms PCB126/kg resulted in a significant increase in hepatic T(4)-glucuronide formation, causing a decline in serum thyroxine and fT(4), and resulting in increased serum thyroid-stimulating hormone (TSH). Serum TSH was also increased in animals that received 7.5 microg PCB126/kg; no other HPT axis alterations were found in these animals. When pretreated with PCB126, the ClO(4)(-) dose trends disappeared, suggesting a less than additive effect on the HPT axis. In dosing study II, animals were given lower doses of PCB126 (0, 0.075, 0.75, or 7.5 microg/kg) on day 0, and followed with ClO(4)(-) (0 or 0.01 mg/kg day) in drinking water beginning on day 1 and continuing for several days to explore transient HPT axis effects. No statistical effects were seen for PCB126 or ClO(4)(-) alone, and no perturbations were found when administered sequentially in dosing study II. In conclusion, these studies demonstrate that HPT axis disturbances following exposure to ClO(4)(-) are less than additive when pretreated with relatively high doses of PCB126. At relatively low doses, at or near the no-observed-effect-level for PCB126 and ClO(4)(-), no interactions between the chemicals occur.
McLanahan
Eva D
ED
Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA. evad@uga.edu
Campbell
Jerry L
JL
Ferguson
Duncan C
DC
Harmon
Barry
B
Hedge
Joan M
JM
Crofton
Kevin M
KM
Mattie
David R
DR
Braverman
Lewis
L
Keys
Deborah A
DA
Mumtaz
Moiz
M
Fisher
Jeffrey W
JW
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006728:Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007454:Iodides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010472:Perchlorates / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000096:biosynthesis / Q000502:physiology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D000099209:Sodium-Iodide Symporters
D006728:Hormones; D007454:Iodides; D010472:Perchlorates; D011078:Polychlorinated Biphenyls; D000644:Quaternary Ammonium Compounds; D027981:Symporters; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters; C023035:3,4,5,3',4'-pentachlorobiphenyl; C053506:ammonium perchlorate