Effects of hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone on serum thyroid hormone levels in rats.
Effects of administration of equimolar doses of hexachlorobenzene (HCB) and its metabolites pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ) on serum thyroxine (TT4) and triiodothyronine (TT3) levels in rats were studied. Furthermore, it was investigated whether the observed effects were related to the serum levels of HCB or PCP. Rats received either corn oil (controls) or HCB, PCP or TCHQ in a single equimolar intraperitoneal dose of 0.056 mmol/kg. Results indicated that HCB did not alter serum TT4 and TT3 levels for a period up to 96 h after dosing. In contrast, PCP and TCHQ were both capable of reducing serum TT4 levels with a maximum effect between 6 and 24 h after exposure. TCHQ was more effective in repressing TT3 than TT4 blood levels. Dose-response experiments were carried out in order to obtain insight into the sensitivity of the observed effects. Rats received different doses of PCP or TCHQ intraperitoneally. The reductions of TT4 levels by PCP were inversely related to serum PCP levels in exposed animals, based on the toxicokinetics and dose-response profiles. Furthermore, PCP serum levels after HCB administration appeared too low to cause an effect. The results of this study indicate that not HCB itself, but rather its metabolites PCP and TCHQ may be involved in reduced serum thyroid hormone levels after HCB administration.
van Raaij
J A
JA
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van den Berg
K J
KJ
Engel
R
R
Bragt
P C
PC
Notten
W R
WR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006581:Hexachlorobenzene / Q000633:toxicity*; D006873:Hydroquinones / Q000633:toxicity*; D008297:Male; D010416:Pentachlorophenol / Q000633:toxicity*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D006873:Hydroquinones; D014284:Triiodothyronine; D006581:Hexachlorobenzene; C044578:2,3,5,6-tetrachlorohydroquinone; D010416:Pentachlorophenol; D013974:Thyroxine