No FIFRA guideline pharmacokinetics or metabolism studies on carbofuran were submitted to
DPR. However, a series of studies from the open literature were available which examined the
handling and disposition of this insecticide in mammals after acute oral, intravenous, dermal, or
inhalation exposure. As detailed in the following sections, hydroxylation (oxidation) and
hydrolysis reactions, along with the appropriate polar conjugations, comprise the major
metabolic transformations of carbofuran, creating esters or ester cleavage products (JMPR,
1996). Metabolism and excretion can be followed using carbofuran labeled in one of two sites
on the molecule: 1. in the carbonyl carbon, which permits analysis of the fate of the carbarnate
group after hydrolysis, or 2. in the benzofuranyl ring, which allows analysis of the fate of the ring
moiety. In the rat, the data using carbonyl-14C-carbofuran indicate rapid absorption by the oral
route, followed by carbamate hydrolysis and excretion either through the lungs (14CO2) or
through the urine and feces. The data using ring-14C-carbofuran indicate rapid excretion,
predominantly in urine. One bile cannulation study demonstrated carbofuran entry into the
enterohepatic circulation. In this manner, appreciable cholinesterase inhibiting activity is
maintained in the blood after the disappearance of the parent molecule. One study suggests
that N-nitroso carbofuran, a mutagenic and cytotoxic derivative, might be formed in the
stomach.
No FIFRA guideline pharmacokinetics or metabolism studies on carbofuran were submitted toDPR. However, a series of studies from the open literature were available which examined thehandling and disposition of this insecticide in mammals after acute oral, intravenous, dermal, orinhalation exposure. As detailed in the following sections, hydroxylation (oxidation) andhydrolysis reactions, along with the appropriate polar conjugations, comprise the majormetabolic transformations of carbofuran, creating esters or ester cleavage products (JMPR,1996). Metabolism and excretion can be followed using carbofuran labeled in one of two siteson the molecule: 1. in the carbonyl carbon, which permits analysis of the fate of the carbarnategroup after hydrolysis, or 2. in the benzofuranyl ring, which allows analysis of the fate of the ringmoiety. In the rat, the data using carbonyl-14C-carbofuran indicate rapid absorption by the oralroute, followed by carbamate hydrolysis and excretion either through the lungs (14CO2) orthrough the urine and feces. The data using ring-14C-carbofuran indicate rapid excretion,predominantly in urine. One bile cannulation study demonstrated carbofuran entry into theenterohepatic circulation. In this manner, appreciable cholinesterase inhibiting activity ismaintained in the blood after the disappearance of the parent molecule. One study suggeststhat N-nitroso carbofuran, a mutagenic and cytotoxic derivative, might be formed in thestomach.
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