Metabolism of benzo[b]thien-4-yl methylcarbamate (Mobam) in rats. Balance study and urinary metabolite separation

The life of methylcarbamate insecticides in the animal body is very short. From 70 to 80% of an administered carbamate dose is usually eliminated, primarily in the urine, by 24 hr. The compounds are metabolized by hydrolytic and oxidative mechanisms and the resulting metabolites are excreted largely as sulfate and/or glucuronide conjugates. Some carbamates are reported to be conjugated directly, forming A-glucuronides, and then excreted.Hydrolysis of the carbamic acid ester results in detoxication of the insecticide. Carbamate metabolites formed by oxidation may be more or less toxic than the original compound. The toxicological properties of the conjugate metabolites have not been critically evaluated. This paper reviews recent findings on carbamate metabolism in animals, with particular emphasis on their metabolism by dairy cows and their residues in the milk.The toxicological significance of most foreign compounds entering the animal body is dependent, in part, on the manner in which they are metabolized. Some chemicals, such as strong bases, strong acids, and highly chlorinated hydrocarbons, are highly resistant to metabolism (Williams, 1963). These compounds, if toxic, would tend to retain their toxic action until excreted from the body. Usually, a chemical entering the body does undergo some type of transformation. The new chemical may be more toxic, less toxic, or equal in toxicity to the original compound. All three of these possibilities are known to occur as the result of metabolic transformation of certain carbamate insecticides by animal systems.The carbamate insecticides are esters of carbamic acid and those discussed herein are monomethyl derivatives of such esters. The first insecticidal carbamates synthesized were dimethyl carbamates (Gysin, 1952;Wiesmann, 1951;Wiesmann et al., 1951) but these did not have adequate insecticidal activity, and emphasis on the development of carbamate insecticides was placed on the more effective methylcarbamates (Casida, 1963;Fukuto, 1961;Kolbezen et al., 1954). The structures and chemical and common names of some of these compounds are given below.Although each of the compounds is a monomethyl carbamate, these three materials demonstrate that the carbamate insecticides are highly variable in their chemical makeup. Additional evidence as to the variability of the chemistry of this

Section: -Benzothienyl Methylcarbamate (Mobam)mentioning

confidence: 99%

Metabolism of insecticidal methylcarbamates in animals

Hw¹

1970

“…was filled to approximately 10 cm. with Porapak (Robbins et a!., 1969). Five milliliters of trioctylamine in 15 ml.…”

Section: Methodsmentioning

confidence: 99%

Dieldrin-14C metabolism in sheep. Distribution and isolation of urinary metabolites

Hedde¹,

Davison²,

Robbins³

1970

Self Cite

Seven sheep were given 165 to 230 microcuries of dieldrin-14C. Three to 14% of the radioactive dose was recovered in the urine over 3-to 6-day periods. This radioactivity was contained in six metabolites, four of which were extracted from urine with hexane and two of which were not. The extraction and isolation of these metabolites are described.That chlorinated hydrocarbon insecticides, such as dieldrin, are accumulated in body fat is well known. However, only recently has the metabolism of dieldrin and related insecticides been reported in animals. Korte and Arent (1965) reported the excretion of dieldrin metabolites in urine and feces of rabbits and rats. They isolated six metabolites from rabbit urine, with one comprising 86% of the total. This metabolite was identified as a trans-diol formed by the addition of water across the epoxide ring. Later,

“…Methyl (p-chlorophenyl tri-o-acetyl-/3-glucopyranosid)uronate was prepared by the method used by Robbins et al (1969) for the synthesis of methyl (4-benzothienyl tri-o-acetyl-S-glucopyranosid)uronate. For the synthesis of p-chlorophenyl glucuronide, 2 g of methyl (p-chlorophenyl tri-o-acetyl-/3-glucopyranosid)uronate was dissolved in 40 ml of boiling ethanol, 2 ml of 1 A KOH was added, and the solution was heated to 65°C for 1 hr.…”

Section: Earliermentioning

confidence: 99%

Metabolism of p-chlorophenyl N-methylcarbamate in the chicken

Paulson¹,

Zehr²

1971

Leghorn hens were given a single oral dose of either p-chlorophenyl-14C(U) A-methylcarbamate (ring label) or p-chlorophenyl jV-methylcarbamate 14C (carbonyl label). When the carbonyl-labeled compound was administered, 69.5 % of the carbon-14 was expired during the 48-hr collection period, whereas no expiratory carbon-14 was detected when the ring-labeled compound was given. Total carbon-14 excreted in the urine accounted for 95% of the activity given as the ring-labeled compound and 14% of the activity given as the carbonyllabeled compound; the feces was a minor route of excretion in both cases (less than 2%). Carbon-14 remaining in the hens 48 hr after dosing accounted for 0.7 and 7.5% of the activity given as the ringlabeled and carbonyl-labeled compounds, respectively. Eggs collected for 8 days after dosing contained 0.27% of the carbon-14 given as a single oral dose of the ring-labeled compound. Urinary metabolites were identified as p-chlorophenyl sulfate (I), p-chlorophenyl glucuronide (II), and p-chlorophenol (III). The feces contained I, II, III, and trace amounts of the parent compound. p-Chlorophenyl-14C(U) Ar-Methylcarhamate p-Chlorophenyl A'-Methylcarbamate-14C % dose/g