TETRACYCLINE
Overview
Chemical Names
4-(DIMETHYLAMINO)-1,4,4a,5,5a,6,11,12a-OCTAHYDRO-3,6,10,12,12a-PENTAHYDROXY-6-METHYL-1,11-DIOXO-2-NAPHTHALENECARBOXAMIDE
CAS number
60-54-8
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT
ANTIMICROBIAL_AGENT
Evaluations
Evaluation year: 1999
ADI:0-0.03 mg/kg bw
ADI:
0-0.03 mg/kg bw
Comments:
Oxytetracycline, tetracycline, and chlortetracycline have a low degree of toxicity. Because the tetracyclines are poorly absorbed from the gastrointestinal tract, high concentrations are readily achieved in the intestine, inducing resistant strains, and altering the metabolic activity and colonization resistance properties of the microflora. Selection of resistant bacterial strains appears to be the most sensitive end-point for use in risk assessment, particularly the selection of resistant Enterobacteriaceae. As individuals show little variation with respect to this effect, the Committee concluded that no safety factor was needed and established an ADI of 0-30 µg/kg bw/d (rounded to one significant figure) for the tetracyclines alone or in combination based on the NOEL of 2 mg/d (equivalent to 33 µg/kg bw per day) from a study in humans. Estimated daily intake at the MRLs for tetracyclines, alone or in combination, would be 0.37 mg/p/d.
MRL Comment:
Group ADI and group MRLs for chlortetracycline, oxytetracycline, and tetracycline, expressed as parent drug, singly or in combination; MRLs (in mg/kg tissue, mg/l milk): Muscle (cattle, pigs, sheep and poultry): 0.2; Liver (cattle, pigs, sheep and poultry): 0.6; Kidney (cattle, pigs, sheep and poultry): 1.2; Eggs (poultry): 0.4; Milk (cattle and sheep): 0.1.
MRL Code:
MRL
Intake:
0.37 mg/p/d, group TMDI
Meeting:
50
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
Clinical study (Tancrede & Barakat, 1987): A dose-related effect of oxytetracycline was seen on intestinal microflora in people given 2, 20, or 2000 mg/d. The effects ranged from elimination of susceptible anaerobes and more resistant Enterobacteriaceae with 2 g/day to decreased in the numbers of susceptible Enterobacteriaceae and increased numbers of resistant strains at 20 mg/d. The NOEL was 2 mg/d.
Animal Specie:
Human
Effect:
Selection of resistant bacterial strains
NOEL:
33 µg/kg bw per day
Point of departure:
33 µg/kg bw per day
Previous Years:
1996, TRS 876-JECFA 47/22, FNP 41/9-JECFA 47/3, FAS 36-JECFA 45/85 (1995). 0-0.003 (1995). GROUP ADI AND GROUP MRLs FOR CHLORTETRACYCLINE, OXYTETRACYCLINE, AND TETRACYCLINE, EXPRESSED AS PARENT DRUG, SINGLY OR IN COMBINATION; MRLs: MUSCLE (CATTLE, PIGS, S
1996, TRS 876-JECFA 47/22, FNP 41/9-JECFA 47/3, FAS 36-JECFA 45/85 (1995). 0-0.003 (1995). GROUP ADI AND GROUP MRLs FOR CHLORTETRACYCLINE, OXYTETRACYCLINE, AND TETRACYCLINE, EXPRESSED AS PARENT DRUG, SINGLY OR IN COMBINATION; MRLs: MUSCLE (CATTLE, PIGS, S