SULFAMETHAZINE
Overview
Chemical Names
4-AMINO-N-(4,6-DIMETHYL-2-PYRIMYDYL) SULFANILAMIDE
Synonyms
SULFAMIDINE; SULFAMETHAZINE
CAS number
57-68-1
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT
ANTIMICROBIAL_AGENT
Evaluations
Evaluation year: 1995
ADI:0-0.05 mg/kg bw
ADI:
0-0.05 mg/kg bw
Comments:
Considering all available information, including the studies evaluated at the 34th meeting, the Committee established an ADI of 0-50 µg/kg bw/day based on an overall NOEL of 5 mg/kg bw/day observed in rats and pigs for changes in thyroid morphology and applying a safety factor of 100. Although it was recognized that primates (including humans) are less susceptible than rats and pigs to the antithyroidal effect of sulfonamides, the Committee noted that in individuals sensitized to sulfonamides, hypersensitivity reactions may occur as a result of the ingestion of sulfadimidine residues in food of animal origin. In line with the previous evaluation, the Committee therefore recommended that the MRLs should be set as low as practically achievable. In doing so, the Committee also recognized that these concentrations would then be below the levels considered significant for microbiological concern.
MRL Comment:
MRLs: Muscle, liver, kidney and fat (cattle, sheep, pigs and poultry): 0.1 (expressed as parent drug, in mg/kg); Milk (cattle): 0.025 (expressed as parent drug, in mg/l); Eggs: no MRL allocated (should not be used in laying hens)
MRL Code:
MRL
Intake:
87.5 µg/p/day TMDI for sulfadimidine residues
Meeting:
42
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
Rat study (McClain et al., 1993a): 20/sex/dose Charles River CD rats were administered via dietary admixture sulfadimidine at dosages of 0, 1, 2.5, 5, 10, 25, 50, 100, 200, 400, or 600 mg/kg bw/d for 4 weeks. At two weeks, 5/dose, and at 4 weeks 15/dose, were killed. Parameters included clinical signs, mortality, body weight, food consumption, T3, rT3, T4 and TSH, gross post mortem examination, thyroid weight, and histopathology of the thyroid gland. A 'thyroid functional morphology index' was determined based on the size of the follicles, the amount and functional properties of follicular colloid, and the follicular-cell height. At 2 and 4 weeks, plasma T4 and T3 levels decreased & TSH increased at >200 mg/kg bw. Significant dose-related increased thyroid weights occurred >200 mg/kg bw. Dose-related increased 'thyroid functional morphology index' and increased incidences of hypertrophy and hyperplasia of thyroid follicular cells were noted, starting at 10 mg/kg. The NOEL in this study was 5 mg/kg bw/d.
Pig study (Cullison et al., 1990b): Male weanling pigs (5/dose) received diets containing 0,125, 250, 500, or 1000 mg sulfadimidine/kg feed (0, 5, 10, 20, or 40 mg/kg bw/d) for 4 weeks. Weekly blood samples were analyzed for TSH, T4, and T3 levels, and thyroid weights & histology were assessed. The following effects were seen in high-dose pigs: increased average TSH levels, decreased T4 levels, and increased thyroid weights. Thyroid follicular hypertrophy or follicular cell hypertrophy and hyperplasia was noted in the 250 mg/kg feed dose group and higher. The NOEL in this study was 125 mg/kg feed, equivalent to 5 mg/kg bw/d.
Animal Specie:
Rats & pigs
Effect:
Changes in thyroid morphology
NOEL:
5 mg/kg bw/day, rats and pigs
Point of departure:
5 mg/kg bw/day, rats and pigs
Previous Years:
1991, TRS 815-JECFA 38/36. 0-0.004 (TEMPORARY). TE. TMRL
1989, TRS 788-JECFA 34/32, FAS 25-JECFA 34/79. 0-0.004 (TEMPORARY) (MRLs: MEAT, LIVER, KIDNEY AND FAT: 0.3 MG/KG AS TOTAL RESIDUE; 0.1 MG/KG AS SULFADIMIDINE; MILK: 0.05 MG/KG AS TOTAL RESIDUE; 0.
1991, TRS 815-JECFA 38/36. 0-0.004 (TEMPORARY). TE. TMRL
1989, TRS 788-JECFA 34/32, FAS 25-JECFA 34/79. 0-0.004 (TEMPORARY) (MRLs: MEAT, LIVER, KIDNEY AND FAT: 0.3 MG/KG AS TOTAL RESIDUE; 0.1 MG/KG AS SULFADIMIDINE; MILK: 0.05 MG/KG AS TOTAL RESIDUE; 0.