At Corvallis, Robbins, et al. (1956) studied the fate of the labeled compound ina 
Guernsey bull calf, Their data on levels in the blood were similar to those reported from 
Kerrville, Cholinesterase in the treated animal was about 40 percent inhibited and was 
recovering 2 weeks after treatment. 
Near quantitative recovery of the administered radioactivity in the urine and feces 
was found by 11 days after treatment. Small quantities of unmetabolized insecticide were 
excreted in the feces, but none in the urine. 
After 14 days the animal was sacrificed and tissue samples were taken for analysis. 
Total radioactivity was highest inthe brain, liver, and kidney, ranging from 9 to 12 p.p.m., 
but only small amounts of the radioactive materials partitioned as unmetabolized insec- 
ticide. Total residues in meat were very low, and less than 0.05 p.p.m. was insecticide, 
Fat samples, however, still contained 7 p.p.m. after 2 weeks. 
In studies at the University of Wisconsin Plapp and Casida (1958) found the rates 
of metabolism in the blood, urine, and feces of a lactating Holstein cow to be similar 
to those reported from Kerrville and Corvallis. In milk taken from the animal 8 hours 
after treatment 32 p.p.m. of the insecticide were present. The amount declined rapidly, 
but 0.4 p.p.m. was still present after a week, Of the total dose 2 percent was secreted in 
the milk. 
After 7 days the cow was sacrificed and tissue samples were taken for analysis. As 
much as 18 p.p.m. of hexane-soluble radioactivity was found in fat samples, but it was 
not determined whether it was all insecticide or included other materials of similar 
solubility. 
The nature of ronnel metabolism was further studied in white rats and houseflies 
(Plapp and Casida, 1958). Since paper chromatographic techniques available at the time 
were unsatisfactory for separating the possible hydrolytic metabolites, an ion-exchange 
chromatographic separation was developed. It was demonstrated that in mammals ronnel 
was subject to hydrolysis at boththe P-0-phenyland P-0-methyl bonds whereas in insects 
hydrolysis occurred largely at the P-0-phenyl bond, The characterization of hydrolytic 
metabolites formed by hydrolysis of the P-0-methyl bond was the first report on com- 
pounds of this type. The amount of metabolites produced by hydrolysis of the P-0-methyl 
bond was much higher in mammals than in insects and it was postulated that this differ- 
ence may account, at least in part, for the lower toxicity of ronnel to mammals than to 
insects. 
Co-Ral,--The second insecticide to be registered for use as an animal systemic was 
Co -Ral (0-(3-chloro-4-methylumbelliferone) 0,0-diethyl phosphorothioate), also knownas 
Bayer 21/199, Preliminary tests with this compound showed that it was only partially 
effective as a systemic when administered orally to cattle (McGregor, et al. 1954), but 
later it was found to be highly active -as a spray (Brundrett, et al. 1957). It is cur- 
rently recommended as a 0.5 percent spray at the rate of 1 gallon per animal, A mini- 
mum of 45 days is required between treatment and slaughter. 
The metabolism and residues associated with the administration of Co-Ral to cattle 
have been extensively studied (Kaplanis, et al. 1959, Krueger, et al. 1959, Robbins, et al. 
1959). When applied as a spray, most of the insecticide remained on the hair and hide, 
Levels in the blood were very low, reaching a maximum of 0.27 p.p.m, in the different 
studies, Maximum ChE depression to about 60 percent of normal occurred | week after 
treatment. Residues in milk were never higherthan 0.1 p.p.m. Only small fractions of the 
dose were excreted in the urine and feces. 
When administered orally, as much radioactivity was excreted in the feces as in the 
urine (34 percent). Large amounts of the material in the feces were unmetabolized 
insecticide, indicating that it was poorly absorbed from the digestive tract. 
165 
