In an animal sacrificed 2 weeks after spraying at 52 mg./kg. the most insecticide 
in any tissue was 0.11 p.p.m. in subcutaneous fat. In a dairy animal sacrificed 6 weeks 
after dermal treatment at 40 p.p.m., residues in all internal tissues were less than 0.06 
p-p-m. However, high residues of unmetabolized insecticide were still present on the 
hide several weeks after treatment. A sensitive chromatographic technique utilizing 
alumina was developed which allows for rapid separation of Co-Ral, its oxygen analog, 
and labeled phospholipids with similar partitioning properties (Krueger, et al. 1959). 
The peculiar property of Co-Ral--poorly effective orally, but systematically active 
dermally--may be ascribed to its chemical structure. Krueger et al, demonstrated 
that the pyrone ring can be opened to form a water-soluble derivative under alkaline 
conditions. When acidified, the ring is reclosed, and so the chemical can be converted 
to a water-soluble material without losing its toxicity. The same property has recently 
been made the basis for several methods of determining Co-Ral residues (Claborn, et al. 
1960, Kane, et al. 1960). lon-exchange chromatography has demonstrated that Co- -Ral, 
like ronnel, is detoxified by hydrolysis of both the P-0-phenyl and P-0O-alkyl groupings. 
There is evidence that the process goes completely to phosphoric acid. In rats differ- 
ences in the route of administration have resulted in differences in the site of hydrolytic 
attack, 
Dimethoate.--Dimethoate (0,0-dimethyl S-(N- methylcarbamoylmethyl) phosphoro- 
dithioate) is another organic phosphorus insecticide that has shown promise as an animal 
systemic, Studies on its toxicology (Hewitt, et al. 1958) and also metabolism and residues 
associated with its oral and intramuscular administration to cattle have been reported 
(Dauterman, et al, 1959, Kaplanis, et al, 1959). 
Oral administration of dimethoate to cattle at 10 mg./kg. caused 30 to 40 percent 
inhibition of RBC ChE, and administration at 40 mg./kg. caused an 80 percent reduction 
in ChE activity and symptoms of poisoning were noted, Highest levels of insecticide in 
the blood occurred 2 to 8 hours after oral treatment and within 1 hour following intra- 
muscular injection, Within 24 hours substantially all insecticide had disappeared from 
the blood, Paper chromatographic evidence was obtained forthe conversion of dimethoate 
to its oxygen analog and for the occurrence of both materials in blood, 
In bioassay studies on the blood of animals treated with the radioactive dimethoate, 
Roberts, et al. (1958) demonstrated the occurrence of a metabolite more toxic to stable- 
flies than the parent compound, The concentration of the metabolite increased as the 
concentration of the insecticide declined, but both were completely dissipated within 24 
hours, 
Dimethoate is the most rapidly metabolized and elirninated compound yet studied. 
About 90 percent of the administered material was accounted for in the urine within 
24 hours of oral and 9 hours of intramuscular treatment. Only trace amounts were 
eliminated in the feces, 
A total of 1.5 p.p.m. of dimethoate plus metabolites was present in the milk of a cow 
8 hours after oral treatment at 9 mg./kg., and it declined to less than 0.02 p.p.m. after 
48 hours. With a cow treated at 40 mg./kg. 4.0 p.p.m. was present in the 0-8 hour milk 
sample, and within 48 hours there was less than 0.04 p.p.m. 
Dimethoate leaves almost no residues in tissues of treated animals. Fat biopsies 
showed that 3 p.p.m. was present after 3 hours, and less than 0.1 p.p.m. after 8 hours. 
In animals treated orally at 10 mg./kg. there was less than 0.1 p.p.m., in all tissues 
within 14 days. 
The metabolism of dimethoate in cattle has been shown to be complex by both paper 
and ion-exchange chromatographic techniques, Kaplanis, et al. (1959) developed an 
acetonitrile:water system that gave excellent separation of a large series of hydrolytic 
metabolites. They found that most of the radioactivity in the urine was an unknown ionized 
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