Suppression of mouse complement activity by contaminants of technical grade pentachlorophenol.
Pentachlorophenol (PCP) is an antimicrobial agent used chiefly for the preservation of wood. Subchronic oral exposure (14 days) to Technical Grade PCP significantly inhibited the functional activity of female B6C3F1 mouse complement when measured in a microtiter hemolytic assay. When evaluated one day following the final exposure the highest administered dose (100 mg/kg) significantly suppressed the Classical complement pathway, the Spontaneous C1 autoactivation pathway, the Alternate pathway and the level of complement component, C3. Reconstitution studies using C5-deficient serum also demonstrated deleterious effects on this complement component. The Classical pathway was the most sensitive to Technical Grade PCP effects. Animals treated with 100 mg/kg Technical Grade PCP had CH 50 levels 30% of vehicle controls. Animals treated for 14 days and allowed a 15 day recovery period had CH 50 values 36% of control and animals which recovered for 30 days had only 52% of the complement activity of control animals. C3 recovery studies also demonstrated continued suppression on days 15 and 30 post-final exposure. Doses of 10 and 30 mg/kg did not produce the marked effects observed with the highest dose; however, a dose-dependent trend was observed for all responses. Animals treated with 100 mg/kg of EC-7, a PCP preparation with reduced amounts of contaminating dioxins and dibenzofurans, did not demonstrate detrimental effects on the complement system.
D000818:Animals; D002733:Chlorophenols / Q000592:standards*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology; D003176:Complement C3 / Q000037:antagonists & inhibitors; D003182:Complement C5 / Q000037:antagonists & inhibitors; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D004340:Drug Contamination; D005260:Female; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010416:Pentachlorophenol / Q000494:pharmacology / Q000592:standards*
D002733:Chlorophenols; D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D003182:Complement C5; D003169:Complement Inactivator Proteins; D010416:Pentachlorophenol