SPECTAM

Overview

Chemical Names
DECAHYDRO-4a,7,9-TRIHYDROXY-2-METHYL-6,8-bis(METHYLAMINO)-4H-PYRANO[2,3- b][1,4]BENZODIOXIN-4-ONE (Also available as DIHYDROCHLORIDE AND SULFATE)
Synonyms
ACTINOSPECTACIN; TROBICIN; M-141; STANILO; SPECTAM; SPECTOGARD; TOGAMYCIN; ANTIBIOTIC 153a
CAS number
1695-77-8
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 1999

ADI:
0-0.04 mg/kg bw

Comments:
The Committee concluded that adverse effects on human gut flora was the most relevant endpoint for establishing an ADI for spectromycin. An ADI of 0-40 µg/kg bw was calculated based on the modal MIC of 16 µg/ml for Bifidobacterium spp, the most sensitive strain, using the following formula: ADI (µg/kg bw) = (16 µg/ml (MIC) x 150 g (daily fecal bolus weight))/1 (fractional bioavailablity) x 1 (safety factor) x 60 kg (weight of adult human)) = 40 µg/kg bw. The Committee concluded that sufficient experimental data had been provided and that no specific factors to account for the range of MICs to cover sensitive bacteria, the anaerobic environment, bacterial density, or pH were required to adjust the modal MIC of 16 to a "microbiological no effect level". The Committee noted that absorption of spectinomycin from the gastrointestinal tract was poor. It therefore adopted a conservative factor which assumed 100% availability of ingested spectinomycin to organisms in the GI-tract.
MRL Comment:
MRLs (expressed as spectinomycin, in mg/kg tissue, mg/l milk): Muscle (cattle, pigs, sheep and chickens): 0.5; Liver and Fat (cattle, pigs, sheep and chickens): 2; Kidney (cattle, pigs, sheep and chickens): 5; Fat (cattle, pigs, sheep and chickens): 2; Milk (cattle): 0.2; Eggs (chickens): 2
MRL Code:
TMRL
Intake:
TMDI 1.8 mg/p/d
Meeting:
50
Report: 
TRS 888-JECFA 50/43
Tox Monograph: 
FAS 33-JECFA 42/59 (1994)
Residues: 
FNP 41/11-JECFA 50/119

Toxicological study

Pivotal Study:
In vitro microbiological study (Kotarski, 1993): Effects of spectinomycin on representative organisms of the human gut flora, including several species of Bifidobacterium, Eubacterium,Bacteroides, Peptococcus, and Fusobacterium were investigated. Many had MIC50 values of greater than 50 µg/ml but Bifidobacteria were more sensitive with MIC values in the range 2-32 µg/ml. The modal MIC for Bifidobacteria was 16 µg/ml with an inoculum density of 106 and 8 µg/ml with an inoculum density of 104.
Animal Specie:
Human GI flora
Effect:
Growth inhibition
Point of departure:
16 µg/ml (modal MIC)
Previous Years:
1994, TRS 851-JECFA 42/22, FNP 41/6-JECFA 42/63, FAS 33-JECFA 42/59. 0-0.004. MRLs (TEMPORARY) (EXPRESSED AS PARENT DRUG; MUSCLE (CATTLE, PIGS AND CHICKENS): 0.3; LIVER (CATTLE, PIGS AND CHICKENS): 2; KIDNEY (CATTLE, PIGS AND CHICKENS): 5; FAT (CATTLE, PI
1994, TRS 851-JECFA 42/22, FNP 41/6-JECFA 42/63, FAS 33-JECFA 42/59. 0-0.004. MRLs (TEMPORARY) (EXPRESSED AS PARENT DRUG; MUSCLE (CATTLE, PIGS AND CHICKENS): 0.3; LIVER (CATTLE, PIGS AND CHICKENS): 2; KIDNEY (CATTLE, PIGS AND CHICKENS): 5; FAT (CATTLE, PI