The 11-hydroxy metabolites of Delta(8).- and Delta(9)-tetrahydrocannabinol are more active than the parent compounds when administered to mice by either the intravenous or intracerebral route. Both Delta(8)- and Delta(9)-tetrahydrocannabinol are rapidly and extensively metabolized by the liver and not by the brain. The hypothesis that the 11-hydroxy metabolites may be the active form of tetrahydrocannabinol is discussed
Summary1. The distribution of A9-tetrahydrocannabinol-14C in the pregnant and nonpregnant mouse is very similar. High concentrations of radiolabel can be seen in the maternal liver, spleen, lungs, brown fat, adrenal glands, mammary glands, yolk sac placenta and corpora lutea. In the pregnant mouse A9-THC crosses the placenta and enters the foetuses in very low concentrations, with no apparent selective intrafoetal radiolabel accumulation sites. Autoradiograms showing the distribution of 14C-cannabinoid 2 h after dosing are presented. 2. A small amount of maternal liver and foetal tissue was removed from the mice, used for autoradiography and extracted with ethyl acetate. Most of the radiolabel in these tissues was solvent extractable and was separated by thin layer chromatography into two fractions, THC and metabolites.3. It appears that most of the cannabinoid is present in a free rather than conjugated fonn.
This study was conducted to determine the threshold concentration of tricresyl phosphate (TCP) in aviation engine oil able to cause delayed peripheral neuropathy in adult hens after repeated exposure. The study also evaluated the predictive value of endpoints usually used to measure acute peripheral neurotoxicity (neurotoxic esterase [NTE] inhibition, ataxia, and histopathologic changes), as measures of neurotoxicity in a subchronic study. Animals that received oil containing 3% TCP showed significant neurotoxicity that could not be accounted for by the small amount of TOCP present. Oil containing 1% TCP was without neurotoxic activity. There was an excellent correlation between percentage inhibition of NTE and development of neuropathy. An association was also seen for ataxia and neuropathology. Further study is needed to determine the phosphate ester isomers responsible for the significant neurotoxic potency demonstrated by the aviation engine oil containing 3% TCP.
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