THE SUBACUTE AND SUBCHRONIC ORAL TOXICITY OF 1,3-DICHLOROPROPANE IN THE RAT

1,3-Dichloropropane (DCP) was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats (10/sex/group). In the 14-day study using dose levels of 200, 600, and 1800 mg/kg/day, all high-dose group animals died, and none died in the other two treatment groups. Other signs associated with treatment in high-dose animals included languid behavior, salivation (also seen in middose group animals), dyspnea, and prostration. No differences were found between animals in the low-dose or middose groups compared to the control animals for body weight, food consumption, hematology, and gross postmortem and histopathology data. Total protein and albumin blood levels were increased for low-dose and middose females, and middose females, respectively. The clinical chemistry findings appeared to be treatment-related, since they were accompanied by significantly increased liver weights (absolute and relative; both sexes of middose animals) and kidney weights (absolute and relative; middose males). The dose levels used in the 90-day study, chosen on the results of the 14-day study, were 50, 200, and 800 mg/kg/day. All animals survived to termination. Males in the high-dose group exhibited a significant decrease in body weight, whereas females in this group exhibited urine-stained fur. No treatment-related effects were found in food consumption or hematology data. Alkaline phosphatase, alanine aminotransferase (males only), albumin, and total protein for high-dose group animals were increased. These findings were accompanied by increases in liver weight for low-dose (females only), middose, and high-dose animals and kidney weights for middose and high-dose group animals. Microscopic evaluations revealed centrilobular hepatocellular hypertrophy for the high-dose group animals and an exacerbation of chronic progressive nephropathy for middose (males only) and high-dose animals. The organ weight, microscopic lesions, and clinical chemistry results together support the conclusion that both hepatic and renal toxicologic effects were produced by the high dose. At the middose, there were essentially no hepatic lesions and a minimal exacerbation of chronic progressive nephropathy in males. However, the organ weight results for both liver and kidney demonstrated patterns related to dosage. In the low-dose animals, no signs associated with treatment were evidenced, except for the increased liver weight for females. Comparison of the effects in this study with DCP to the chemical analog 1,2-dichloropropane revealed that the two compounds have different target organs. The latter toxicant produces hematopoietic and splenic effects.