Continuing education for gastroenterology recertification.
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Biomedical subjects
Publications and source records attributed to L S Andrews.
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The subchronic inhalation toxicity of methanol was evaluated in rats and monkeys. Animals were exposed to 0, 500, 2000, and 5000 ppm methanol vapor for 6 h/d, 5 d/w, for 4 wk. The only treatment-and dose-related effect noted was that of mucoid nasal discharge in rats, which was considered reflective of upper respiratory tract irritation. No consistent treatment-related effects were found for organ or body weights or for histopathologic or ophthalmoscopic examinations. Overall, these findings support the use of the present American Council of Governmental Industrial Hygienists threshold limit value (TLV) of 200 ppm and short-term exposure limit (STEL) of 250 ppm for exposure to methanol vapor.
Multifunctional acrylates and methacrylates (MFA) represent a class of materials with considerable chemical reactivity that are used in many applications with opportunity for contact exposure. They represent appreciable eye and skin contact hazards, and several members of the class may be absorbed from skin to cause systemic effects. A number of MFAs have been identified as sensitizers. While the acute toxicity of MFAs is certain, the effects of repeated or chronic exposure are less clear. Data are presented that suggest that MFAs are not appreciable fetotoxic or teratogenic hazards and do not elicit a strong carcinogenic response following chronic dermal exposure. The use of these data for product safety purposes and research needs is discussed.
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N-hydroxyphenacetin glucuronide has been previously shown to be an unstable compound (half-life 8.7 h) that breaks down to phenacetin, 2-hydroxyphenacetin glucuronide, acetaminophen, acetamide, and a deethylated metabolite that covalently binds to protein. Evidence was presented that the acetamide, acetaminophen and a compound that binds covalently were formed from a common intermediate which was postulated to be N-acetylimidoquinone. In the presence of phosphate buffer, 3-hydroxyphenacetin phosphate is formed at the expense of acetaminophen, acetamide and covalent binding. Phosphate buffer, however, only partially blocks covalent binding to protein suggesting that two deethylated reactive metabolites are formed that can covalently bind to protein. These metabolites also may be converted to acetaminophen but only one of them leads to acetamide. Since the phosphate conjugate contains the ethyl group apparently a third reactive intermediate, which can react with phosphate but not with protein, serves as a precursor of one of the metabolites.
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Benzo(a)pyrene hydroxylase activity was found in the bone marrow of control and 3MC-induced New Zealand white rabbits. This activity was localized in the microsomal fraction, was NADPH dependent and CO sensitive. The reaction was inhibited by 7,8-benzoflavone indicating that it was mediated by the 3MC-inducible form of cytochrome P-450. BP hydroxylase activity in rabbit bone marrow was located primarily in white cells, and was considerably higher than that previously reported for cultured human lymphocytes and monocytes. A possible role for the bone marrow mixed-function oxygenase in the production of hemopoietic toxicity is considered.
During the sulfation of N-hydroxy-2-acetylaminofluorene (NOH-2AAF) by rat liver 100,000 g supernatant fraction in vitro, an unidentified metabolite is produced which accounts for 22% of the N-OH-2AAF metabolized. This product has been characterized as the 2AAF dimer, 1-(N-2'-fluorenylacetamido-2-acetylaminofluorene) by comparing its TLC, HPLC, UV, and mass spectral properties with a synthetic standard which was prepared from the reaction of N-acetoxy-2-acetylaminofluorene (N-AcO-2AAF) with 2AAF. Increasing amounts of 2AAF added to the incubation mixture of N-OH-[acetyl-14C]2AAF and rat liver 100,000 g supernatant fraction decreased the irreversible binding of 14C to protein, and increased the formation of 2AAF dimer proportionately. This suggests that the 2AAF dimer is formed from the reaction of 2AAF and the electrophilic species produced from the sulfated N-OH-2AAF. In the presence of the 9,000 g fraction of rat liver, the dimer of 2AAF was aroximately 1/25 as active as 2AAF in producing mutations in the Salmonella mutagenesis test system.