Subsurface soil from a National Priorities List landfill containing about 2.5% polychlorinated biphenyls (PCBs) was extracted and the extract cleaned by Florisil slurry and alumina column chromatography. The refined extract contained 48 mg/mL PCB, mainly trichlorobiphenyls and tetrachlorobiphenyls, traces of polychlorinated naphthalenes, 125 micrograms/mL 2,2-bis-p-chlorophenyl-1,1-dichloroethylene (DDE), and low levels of chlorinated dibenzofurans. The refined extract was dissolved in corn oil and administered intraperitoneally to weanling (day 20) female rats on days 20 and 21; rats were terminated on day 22. Limited data indicated possible hematopoietic effects, including neutrophilia. There were no changes in relative uterus, kidney, or adrenal gland weights between total doses of 3 to 96 mg/kg total PCB. Relative liver weights increased significantly at 36 mg/kg and activities of P450s 1A1 (as ethoxyresorufin O-dealkylase) and 2B (as pentoxyresorufin O-dealkylase) increased at 12 mg/kg and plateaued at 36 (P450 1A1) or 48 (P450 2b) mg/kg. Serum total thyroxine (T4) declined significantly at doses of 36 mg/kg and greater; thyroid follicular epithelial cells were significantly larger within the same dose range, but the follicular colloid area decreased to less than 60% control values at 12 mg/kg and remained at this size through 72 mg/kg. Maximum mobilization of T4 apparently occurred at 12 mg/kg and attenuated measured declines in circulating levels. Even though a large proportion of proven and probable estrogenic chlorobiphenyls (CBs) were present, the lower amounts of more potent antiestrogenic aryl hydrocarbon (Ah) receptor agonists and/or decreased responsiveness because of low serum T4 levels may have antagonized the uterotropic response.
Weanling female Sprague-Dawley rats were given either 2 or 5 consecutive daily doses of 30 mg/kg 2,2',4,4'-tetrachlorobiphenyl (CB 47) or a total dose of 120 mg/kg Aroclor 1242 divided into 2, 3, or 5 daily doses by intraperitoneal injection. One day after the final dose, serum total thyroxine (T4) was determined and thyroid glands were collected and prepared for morphometric analysis. Serum T4 increased between 20 and 25 d of age, but declined to 35-52% of controls by d 25 in PCB-treated rats. In rats receiving only 2 doses of CB 47, the declines in serum T4 were more modest but the thyroid follicular epithelial cell height increased from 9 microns to 10-12 microns and the colloid area decreased from 1100 microns2 to 800-900 microns2. In Aroclor 1242-treated rats, follicular cell height increases and colloid area decreases were somewhat greater; serum T4 was higher (partially restored) in the rats having received earlier doses. The rapid response of the thyroid gland to moderate decreases in serum T4 attenuates the observed decrease in T4 and may mask effects on T4 metabolism in short-term structure-activity studies. Morphometric measurements may be helpful in characterizing early and/or transient responses to toxicants such as PCBs that have multiple endocrine disrupting effects.
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