Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry

Abstract

Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5–1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with 131I-sodium-iodohippurate and 125I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained. ImagesFIGURE 6.FIGURE 7.

Effects of PBBs on cattle. IV. Distribution and clearance of components of firemaster BP-6.

“…Claims that PBB causes toxic responses and death among dairy animals environmentally contaminated with trace levels of the compound must be seriously questioned, as we still have healthy animals on experiment with PBB concentrations up to and exceeding 30 ppm. Along with the information on the distribution of PBB in cattle, we have developed a broad base of information on the clinical (9, 10, 20, 21), pathological (14,22), and target organ (11,23) effects of exposed animals. These studies are continuing to develop a data base of residue and clinical information for the lifetime of remaining experimental animals.…”

Toxicity of polybrominated biphenyls (PBBs) in Domestic and laboratory animals.

“…Gupta and Moore (76) showed that PBBs are more toxic when given in small repeated doses versus a single acute dose. In most acute and chronic feeding studies, signs of PBB toxicity include weight loss or a decreased weight gain, and an increase in liver size (76)(77)(78)(79)(80)(81)(82)(83)(84)(85). Weight loss is not necessarily accompanied by decreased food intake (76,81) suggesting that PBBs may cause poor feed utilization.…”