Animal studies vehicle control

In an earlier study, there were renal tubular cell adenomas in 5/50 Osbome-Mendel rats receiving doses of 212 mg/kg/day but no tumors in 49 animals receiving 423 mg/kg/day or in 20 vehicle control rats (Weisburger 1977). Despite the lack of tumors, there was a high incidence of nephropathy (18-66%) in exposed male and female rats. 

In studies conducted using animals, evidence of carcinogenicity from 1,4-dichlorobenzene exposure is based on 2-year oral studies in mice and rats. 1,4-Dichlorobenzene was administered by gavage to male rats at doses of 150 mg/kg/day and 300 mg/kg/day, and to female rats and mice of both sexes at doses of 300 mg/kg/day and 600 mg/kg/day. There was a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidneys of male rats. There were no tubular cell tumors in dosed or vehicle-control female rats. There was a marginal increase in the incidence of mononuclear cell leukemia in dosed male rats compared with either vehicle controls or historical controls (NTP 1987). Based on the finding of renal tumors in this study, 1,4-dichlorobenzene was found to be carcinogenic in male rats. 

The test chemical is typically administered directly into the stomach by gavage, which is a requirement of EPA and some other regulatory agencies. This method of dosing allows a precise calculation of the amount of test material received by the animal. Studies typically have three dose levels and a control group that receives the vehicle used for test material delivery. The high dose level is chosen to be one at which some maternal toxicity is known to occur, but never one that would cause more than 10% mortality. The low dose should be one at which no maternal toxicity is apparent, and the intermediate dose(s) should be chosen as a predicted low effect level. 

The dose levels for repeated dermal toxicity studies in animals should have at least three concentrations, including an appropriate vehicle control. Except for treatment with the test chemical, the control group should be handled in a manner identical to the test group. The highest-dose level should not produce evidence of toxicity attributable to the test chemical. 

Metabolic blood parameters are assayed in anesthetized male rats using a modified method of glucose clamp studies in rodents (Terrettaz and Jeanrenaud 1983). Four to 6 rats per group (vehicle control and one dose of the candidate compound) are used. Rats are anesthetized with an intraperitoneal injection of pentobarbital sodium (60 mg/kg), tracheotomized, and one jugular vein per rat is cannulated for intravenous infusion the other vein is prepared for collection of blood samples. Anesthesia is maintained for up to 7 hours by subcutaneous infusion of pentobarbital sodium (adjusted to the anesthetic depth of the individual animal about 24 mg/kg/h). Body temperature is monitored with a rectal probe thermometer, and temperature is maintained at 37 °C by means of a heated surgical table. Blood samples for glucose analysis (10 il) are obtained from the tip of the tail every 15 minutes, and for lactate analysis (20 p.1) every... 

Two sources reported the results of a study of rats administered sodium selenate or sodium selenite in the diet for a lifetime (Harr et al. 1967 Tinsley et al. 1967). A vehicle control and two positive control groups (administered a known hepatocarcinogen, V-2-fluorenyl-acetamide [FAA]) were included. Mortality was high in the highest dose group (0.8 mg selenium/kg/day), and therefore, selenium administration was discontinued. Longevity was reduced in animals fed 0.4 mg selenium/kg/day, but not... 

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