Characterization of trihalomethane (THM)-induced renal dysfunction in the rat. II: Relative potency of THMs in promoting renal dysfunction.
Single non-lethal doses (3 mmol/kg) of chloroform (CHCl3), dichlorobromomethane (CHCl2Br), dibromochloromethane (CHClBr2), and bromoform (CHBr3) were administered by intraperitoneal injection to male Sprague-Dawley rats and proximal tubular secretion and reabsorption was assessed at varied times following treatment. Each of the trihalomethanes (THMs) at this dose inhibited proximal tubular secretion, as indicated by decreased in vitro renal cortical slice accumulation of organic anion p-aminohippuric acid (14C PAH). The time of maximal THM interference with 14C PAH uptake occurred at 8 h, with recovery being demonstrated by 48 h. Each of the THMs also demonstrated interference with tubular reabsorption, as assessed by urinary glucose excretion, with maximal interference occurring during the first day post-treatment and recovery being observed during the second day post-treatment. In each case, CHCl2Br was the most potent inhibitor of proximal tubular function. Combining these data with those of the preceding paper, the relative potency in disrupting renal function was, in general, CHCl2Br > CHCl3 > CHClBr2 > CHBR3. Since the time course of this investigation indicates that proximal tubular dysfunction precedes other THM-induced renal function interferences, it also appears that proximal tubular damage is the primary event leading to further manifestations of renal dysfunction.
Kroll
R B
RB
Department of Biological Sciences, Towson State University, Maryland 21204.
Robinson
G D
GD
Chung
J H
JH
D000818:Animals; D005617:Chlorofluorocarbons, Methane / Q000633:toxicity*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005617:Chlorofluorocarbons, Methane