Ecological chemistry. LXXXIII. In vitro metabolism of polychlorinated biphenyls-14-C.
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Biomedical subjects
Publications and source records attributed to F Coulston.
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The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) containing 0.05 ppm of tetrachlorodibenzo-p-dioxin, was administered to pregnant rhesus monkeys daily from Day 22 through Day 38 of gestation. At the dose levels administered, 0.05 mg/kg, 1 mg/kg, and 10 mg/kg, no evidence of toxicity was seen in the mother and no evidence of teratogenicity was seen in any of the offspring. Observations of the infants for 1 year following birth indicated that there was no toxicity due to the 2,4,5-T.
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The biological effects of airborne particulate lead were studied in rats and rhesus monkeys (Macaca mulatta) exposed nearly continuously (22 hours per day) at a concentration of 21.5 mug Pb/cubic meter of air. The year-long exposure elicited an increase in the concentration of lead in the blood to 28 mug/100 ml in the rats and 17 mug/100 ml in the monkeys. Levels of lead in control animals were about 5 mug/100 and 4 mug/100 ml, respectively, in the rats and monkeys. The elevated blood-lead levels reached a maximum during the first few months of exposure and did not increase significantly after that time. Elevated concentrations of lead were also detected in lung, liver, kidney and bone of both species. While concentrations of lead were nearly always less than 1 mug/g in control animals, they rose to 2-3 mug/g in soft tissues of exposed animals and up to 6 mug/g in bone. Differences between lead levels in animals exposed six months or twelve months were very small. The concentration of lead decreased in the soft tissues of animals removed from the chamber after one year's exposure but remained elevated in bone. The activity of the enzyme delta-amino-levulinic acid dehydrase (ALAD) in circulating erythrocytes was inhibited about 70% in rats exposed to the airborne lead. No reduction of the enzyme activity occurred in brain or liver tissue of either the rats or monkeys. Normal levels of ALAD in erythrocytes of the monkeys were too low to permit meaningful measurements. In spite of the reduced ALAD activity in rat erythrocytes, there was no concomitant alteration in the excretion of heme precursors. In all other respects, there appeared to be no deleterious effects on the animals from exposure to the airborne particulate lead. No changes were detected in serum chemistry or hematology nor were there any gross, microscopic or ultrastructural pathologic changes observed.
Two experiments were conducted to determine the effects of low-level exposure to airborne lead particulates on humans. Male volunteers were exposed 23 hours per day for about 18 weeks to either 10.9 mug Pb/m3 or 3.2 mug Pb/m3 of air. The particulate matter consisted primarily of sub-micron sized particles of alpha lead dioxide. During exposure to 10.9 mug Pb/m3, the mean blood-lead level of the men increased to 37 mug/100 ml while the level in controls remained at about 15 mug/100 ml. Exposure to 3.2 mug Pb/m3 elicited an increase in blood-lead to about 27 mug/100 ml. In both cases, the blood-lead levels appeared to plateau after about three months of exposure and subsequent to that, no further increases were observed. About two months after the men left the exposure chamber, their blood-leads returned to near normal levels. Although urinary excretion of lead was always within the limits usually considered normal, there was a definite increase in urinary lead in the men exposed to 10.9 mug Pb/m3 and a somewhat smaller increase in the men exposed to 3.2 mug Pb/m3. The activity of delta-aminolevulinic acid dehydrase was reduced by about 50% in the erythrocytes of men exposed to 10.9 mug Pb/m3, but returned to normal after exposure was terminated. Practically no changes in the activity of the enzyme were noted in the men exposed to 3.2 mug Pb/m3. Exposure to either level of particulate lead did not cause measurable changes in the excretion of heme precursors nor were there any alterations of serum chemistry or hematology profiles in any of the men.
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The separation and identification of hexachlorobenzene (HCB), pentachlorobenzene (QCB), and pentachlorophenol (PCP) by thin layer, high-pressure liquid, and gas chromatography are reported. Satisfactory results were obtained with reverse phase thin layer and high-pressure liquid chromatography. The 2 gas chromatographic columns tested gave adequate separation of HCB and QCB. A PCP methylation process using dimethyl sulfate was attempted. Procedures are presented for extraction, cleanup, separation, and identification of HCB and possible metabolites from feces of a rhesus monkey treated with 14C-HCB. Recovery of radioactivity in excess of 96% was attained in extracts from feces by these methods. Preliminary evidence suggests the formation of PCP and possibly other polar metabolites from HCB in the rhesus monkey.
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