Laboratory Studies of the Effect of U-5897 on the Reproduction of Wild Male Rats

Abstract

The effects of U-5897 (3-chloro-l,2-propanediol), a male chemosterilant that acts by inducing epididymal lesions, were tested in the laboratory on ricefield rats (Rattus argentiventer), Polynesian rats (R. exulans), black rats (R. rattus), Norway rats (R. norvegicus), and laboratory rats (Long-Evans strain). For each species, seven treatment groups of five males each were given single oral doses ranging from 0-300 mg/kg. No lesions were induced in ricefield and Polynesian rats at any dose level. Some Norway and laboratory rats developed lesions at doses of 50 mg/kg, and all developed them at 100 mg/kg and above. Black rats developed lesions at 100 mg/kg, and higher, but the response was incomplete; at least one male at each dose level failed to develop lesions. Some Norway, laboratory, and Polynesian rats died from doses of 200 mg/kg and higher. The concept of controlling wildlife populations by interfering with one or more of the reproductive processes was discussed by Davis (1961), and attempts to apply the concept have been reported by several workers (Balser 1964, Linhart and Enders 1964, Linhart et al. 1968, Howard and Marsh 1969). Because reproductive inhibitors have advantages over traditional control chemicals in both safety and specificity, there is considerable interest in finding effective ones for use against species causing damage. One possible compound for rats is U-5897, a chlorohydrin. It was first shown to have a reversible antifertility effect in male monkeys, (Macaca mulatta), guinea pigs (Cavia cobaya), and white rats (Kirton et al. 1970, Ericsson and Youngdale 1970). Subsequent studies revealed that male white rats are permanently sterilized when given single oral doses of 45 mg/kg, approximately five times the minimum dose that produces reversible antifertility (Ericsson 1970). In both instances, the compound is a post-testicular artifertility agent that apparently does not affect libido (Ericsson 1970, Ericsson and Baker 1970). Sterility 1 Simonsen Laboratories, Gilroy, California. 508 induced in white rats is due to the formation of a lesion in the caput epididymidis that completely blocks passage of sperm to the exterior. Recently Ericsson and Connor (1969) reported that Norway rats also develop the epididymal lesion when treated by gavage or via drinking water. The unique properties of this compound suggested it might be a useful male sterilant for rat species causing agricultural damage. Accordingly, we tested its effects on Polynesian, black, ricefield, and Norway rats, and on laboratory rats for comparison.