Sulfamethazine

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    Jennifer
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    General Description

    Synonyms: 4-Amino-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide; N(Sup 1)-(4,6-dimethyl-2-pyrimidinyl) Sulfanilamide; Diazil; Diazyl; Sulfamezathine; Sulfamethiazine; Sulfisomidine; Superseptil; Sulmet; Pirmazin; Primazin; Sulfadimerazine
    OSHA IMIS Code Number: S228
    Chemical Abstracts Service (CAS) Registry Number: 57-68-1
    NIOSH Registry of Toxic Effects of Chemical Substances (RTECS) Identification Number: WO9275000
    Chemical Description and Physical Properties:
    white or yellowish-white crystalline powder, with slightly bitter taste
    molecular weight: 278.36
    molecular formula: C12H14N4O2S
    Health Factors
    Carcinogenic Classification:
    International Agency for Research on Cancer (IARC): Group 3, Not classifiable as to its carcinogenicity to humans
    Potential Symptoms: In rats and mice: thyroid cancer
    Notes:
    Sulfamethazine is primarily used as a veterinary antibacterial drug in food animals and has been detected in airborne dust collected from a pig-fattening farm.
    The FDA regulates the amount of sulfamethazine residue allowed (0.1 ppm) in uncooked edible tissues of chickens, turkeys, cattle and pigs (21 CFR 556.670).
    Its major urinary metabolite is N-acetyl sulfamethazine, which is produced by the NAT2 isoform of arylamine N-acetyl-transferase, an enzyme in liver and red blood cells that displays polymorphism.
    Sulfamethazine has been used as a tool for phenotyping people as slow acetylators or fast acetylators for NAT2 substrates.
    Sulfamethazine-induced thyroid cancer is thought to involve a cascade of effects starting with the inhibition of the enzyme thyroid peroxidase, leading to decreased thyroxine synthesis, with a consequent increase in thyroid stimulating hormone (TSH) secretion from the pituitary. The excessive TSH then stimulates thyroid hypertrophy and hyperplasia in rodents. This cascade is not known to occur with sulfamethazine exposure in humans.
    Although sulfonamide antimicrobial drugs as a class are known to cause adverse hypersensitivity reactions, especially skin reactions, a recent review of “sulfa allergy” did not cite any cases or studies involving sulfamethazine.
    Literature Basis:
    Choquet-Kastylevsky, G., Vial, T. and Descotes, J.: Allergic adverse reactions to sulfonamides. Curr. Allergy Asthma Rep. 2(1): 16-25, 2002.
    Hamscher G., Pawelzick, H.T., Sczesny, S., Nau, H. and Hartung, J.: Antibiotics in dust originating from a pig-fattening farm: a new source of health hazard for farmers? Environ. Health Perspect. 111(13): 1590-1594, 2003.
    Poirier, L.A., et al.: An FDA review of sulfamethazine toxicity. Regul. Toxicol. Pharmacol. 30(3): 217-222, 1999.
    Vree, T.B., Hekster, Y.A., Nouws, J.F. and Baakman, M.: Pharmacokinetics, metabolism, and renal excretion of sulfadimidine and its N4-acetyl and hydroxy metabolites in humans. Ther. Drug Monit. 8(4): 434-439, 1986.
    Date Last Revised: 10/27/2005

    Monitoring Methods used by OSHA
    Primary Laboratory Sampling/Analytical Method (SLC1):
    Glass Fiber Filter (37 mm)
    analytical solvent: Methanol
    maximum volume: 120 Liters
    maximum flow rate: 1.0 L/min
    current analytical method: High Performance Liquid Chromatography; HPLC/UV
    method reference: OSHA Salt Lake Technical Center In-House File
    method classification: Not Validated
    note: OSHA personnel may obtain E-PERM sampler from the Salt Lake Technical Center.
    Conditions: Column: C18; Mobile Phase: 50:50:0.2 Methanol:Water:H3PO4; Detector Wavelength: 280 nm; Detection Limit: Source of material: FDA

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