The effect of chlorinated paraffins on hepatic enzymes and thyroid hormones.
Male rats and mice were administered chlorinated paraffins (CPs) by daily gavage in corn oil for 14 days. Chlorowax 500C (short chain CP with 58% chlorination), Cereclor 56L (short chain CP with 56% chlorination) and Chlorparaffin 40G (medium chain CP with 40% chlorination) were the CPs studied at dose levels of 0, 10, 50, 100, 250, 500 and 1000 mg/kg for both rats and mice. The no effect levels for hepatic peroxisome proliferation for the above chemicals, as determined by the CN- insensitive palmitoyl co-enzyme A beta-oxidation (PCO) assay, were calculated as 184, 600 and 473 mg/kg and 180, 120 and 252 mg/kg for rats and mice, respectively, whilst those for percent liver weight/body weight were calculated as 74, 51 and 31 mg/kg and 215, 70 and 426 mg/kg for rats and mice, respectively. The short chain CPs were more potent peroxisome proliferators than the medium chain CP, with the mouse proving to be more responsive than the rat. Rats administered the highest dose of CPs showed a depressed plasma thyroxine (T4) level, with a concomitant increase in the plasma concentrations of thyroid stimulating hormone (TSH). The decreased plasma T4 levels appeared to be the result of increased T4 glucuronidation.
Wyatt
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ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Coutts
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CT
Elcombe
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CR
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006843:Hydrocarbons, Chlorinated / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008830:Microbodies / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010232:Paraffin / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
D006843:Hydrocarbons, Chlorinated; C010555:chlorowax 500C; D010232:Paraffin; C079915:chloroparaffin 40G; D013972:Thyrotropin; D013974:Thyroxine