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THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM
Citation:
McDonald, A, Y M. Sey, AND J E. Simmons. THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM. Presented at SOT, San Francisco, CA, March 25 - 29, 2001.
Description:
THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containing organic matter results in the production of a variety of halogenated byproducts, including trihalomethanes (THMs) such as chloroform (CHC13). Exposure to CHC13 is virtually ubiquitous across all segments of the U.S. population, including the aged. The objective of the present study was to evaluate the influence of advanced age on the hepatic and renal toxicity of CHCl3. Young (-90 day old) and aged (22-24 months old) male F-343 rats were administered 0, 0.5, 1.0 or 2.0 mmol CHC13/kg by oral gavage in an aqueous vehicle (10% Alkamuls? at a gavage volume of 5 ml/kg at - 3 p.m.). Hepatotoxicity was assessed at 48 hr by serum SDH, ALT and AST. In both young and old rats, the hepatotoxic response to CHC13 was less at 48 hr than we have previously seen at 24 hr (McDonald et al., 2000), indicating that recovery was underway at this time. As at 24 hr, the differences between young and old rats at 48 hr were greatest at the highest dosage. At 24 hr and 2.0 mmol CHC13/kg, mean serum ALT, AST and SDH values were between 4- and 7-fold greater in the old rats. In contrast, at 48 hr, the maximum difference between young and old rats in these serum indicators was - 2-fold. Nephrotoxicity was assessed by analysis of urinary markers in urine collected at 0, 18 and 42 hr. Several markers of nephrotoxicity, notably urinary LDH and AST revealed apparent dose-, time- and age-dependency; response increased with dose, time after dosing and age. For other urine indicators, base-line levels in old and young animals differed. Urinary glucose and gamma-glutamyl transferase (normalized to urinary creatinine) were elevated consistently in young rats relative to old rats, both in control rats across the 3 time points and in CHC13-exposed rats prior to dosing. In conclusion, these data suggest that advanced age alters the hepatic and renal response to CHC13, indicating that the aged may be a susceptible subpopulation to THMs. (Abstract may not reflect EPA policy.)