compound partially extractable from acidified urine with chloroform. The paper- 
chromatographic technique developed in that study has found wide application in studies 
of the metabolism of other organophosphorus insecticides. 
Using ion-exchange chromatography, Dauterman, et al. (1959) also separated a large 
series of dimethoate metabolites. They showed that the major unknown metabolite was the 
carboxylic acid derivative formed by hydrolysis at the carbamoyl bond. They further 
showed that in both cattle and white rats the insecticide was detoxified by hydrolysis at 
all the possible esteratic sites. 
Ruelene.--Another compound to undergo recent extensive testing as an animal sys- 
temic is Ruelene (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate), This 
insecticide is effective against cattle grubs either orally or as a spray. Preliminary 
data on its effectiveness and toxicology have been published (Dow ACD Bulletin 1959). 
The metabolism of Ruelene has been investigated at Kerrville, Tex., and Corvallis, 
Oreg., following dermal and intramuscular administration to cattle. Studies thus far have 
shown that the insecticide is absorbed most rapidly following intramuscular treatment, 
peak levels in the blood occurring after 6 hours and after 12 hours following dermal treat - 
ment, 
Excretion of hydrolytic metabolites of the insecticides occurs fairly slowly and is 
incomplete. With orally and intramuscularly treated animals 35 to 42 percent of the dose 
was recovered in the urine and feces within 2 weeks. Following dermal administration 
recovery was considerably lower. 
The poor recovery of metabolites of Ruelene in the excretory products indicated that 
large amounts of the insecticide might remain in treated animals. Upon sacrifice, the 
total radioactivity was high in a number of tissues. However, fractionation showed most 
of this to be phosphoric acid and that there was almost no unmetabolized insecticide, 
residues being less than 0.1 p.p.m. It is therefore apparent that the metabolism of the 
insecticide goes completely to phosphoric acid and that the phosphate so produced is 
incorporated into the normal phosphorus metabolism of the animal, 
That this metabolism is complex and complete has been indicated by paper and ion- 
exchange chromatographic studies. From 7 to 11 metabolites have been observed, At 
present, however, they are incompletely characterized, and it is not possible to outline a 
metabolic pathway for the insecticide. 
CONCLUSIONS 
Many facets of the problems involved in the use of systemic insecticides in animals 
need further study. Among the most urgent is the treatment of dairy animals, All the 
compounds studied thus far which show systemic activity have been secreted in the milk, 
although often at very low levels, Residues in milk have been much lower in animals 
treated dermally than in those treated orally. However, with dermal treatments there 
is the problem of continuous slow absorption and the possibility that trace amounts of 
insecticide might be present for some time, 
The data available show that a high degree of cattle grub control can be obtained 
with levels of insecticide that leave no toxic residues present in edible tissues. Control 
can be obtained with both oral and dermal treatments and, possibly, by intramuscular 
injection, 
Much of our present knowledge of the metabolism of organic -phosphorus insecticides 
has been gained through studies of systemics. Techniques developed in these studies 
have found wide applications in investigation of such problems as the metabolism of 
insecticides in resistant and susceptible strains of insects. From these studies has come 
a considerable understanding of the fate of insecticides in both insects and mammals, 
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