DIHYDROSTREPTOMYCIN

Overview

Chemical Names
O-2-DEOXY-(METHYLAMINO)-alpha-L-GLUCOPYRANOSYL-(1–>2)-O-5-DEOXY-3C- (HYDROXYMETHYL)-alpha-L-LYXOFURANOSYL-(1–>4)-N,N'-bis(AMINOIMINOMETHYL)-D- STREPTAMINE
CAS number
128-46-1
Functional Class
Veterinary Drug
ANTIMICROBIAL_AGENT

Evaluations

Evaluation year: 2002

ADI:
0-0.05 mg/kg bw

Comments:
The Committee noted the long history of use of dihydrostreptomycin and streptomycin and the absence of literature reports of adverse effects other than ototoxicity. Due to very low oral bioavailability in humans, consumption of residues of dihydrostreptomycin or streptomycin in animal products presents no risk to peri- or postnatal human health. The 43rd Committee determined that the most sensitive toxic effect was decreased weight gain in a two-year oral toxicity study in rats with dihydrostreptomycin. The present Committee used the NOEL of 5 mg/kg bw/d from this study, with application of a safety factor of 100, to establish a group ADI of 0-50 µg/kg bw for the combined residues of dihydrostreptomycin and streptomycin.
MRL Comment:
MRLs (as dihydrostreptomycin + streptomycin): Milk (cattle and sheep): 0.2 mg/kg. The MRLs recommended at the fifty-second meeting (1999): 600 μg/kg for muscle, liver and fat of cattle, pigs, sheep and chickens; 1000 μg/kg for kidney from cattle, pigs, sheep and chickens.
MRL Code:
MRL
Intake:
TMDI: 0.62 mg/p/d (including milk), 0.32 mg/p/d (not including milk)
Meeting:
58
Report: 
TRS 911-JECFA 58/26
Tox Monograph: 
FAS 39-JECFA 48/39 (1997)
Residues: 
FNP 41/14-JECFA 58/37

Toxicological study

Pivotal Study:
2-year rat study (Wazeter & Goldenthal, 1972): Dihydrostreptomycin was administered in the diet to Charles River CD rats, (25/sex/group), to achieve dosages of 0, 1, 5, or 10 mg/kg bw/d, for 2 years (dietary concentrations were adjusted weekly to compensate for changes in food consumption and bodyweight). Two control groups were included in the study. 12 to 17 out of 25 rats/sex in treated groups had survived up to two years. Body-weight gain was reduced in males in the high-dose group compared to control group 2, but not control group 1. Although this study did not meet current standards regarding the number of animals, the Committee concluded that survival of more than 50% of all treated animals in the 2-year phase of the study (24/50, 33/50, and 29/50 in the low-, mid-, and high-dose groups, respectively), represented an adequate test of the carcinogenic potential of the compound. The NOEL was 5 mg/kg bw/day based on decreased body-weight gain in males at the high dose.
Animal Specie:
Rat
Effect:
Decreased weight gain
NOEL:
5 mg/kg bw/d
LOEL:
10 mg/kg bw/d
Point of departure:
5 mg/kg bw/d
Previous Years:
1999, TRS 893-JECFA 52/20, FNP 41/12-JECFA 52/21, FAS 39-JECFA 48/39 (1997). 0-0.05 mg/kg bw (1997). MRLs (EXPRESSED AS THE SUM OF THE CONCENTRATIONS OF DIHYDROSTREPTOMYCIN AND STREPTOMYCIN): MUSCLE, LIVER AND FAT (CATTLE, SHEEP, PIGS AND CHICKENS): 0.6 m
1999, TRS 893-JECFA 52/20, FNP 41/12-JECFA 52/21, FAS 39-JECFA 48/39 (1997). 0-0.05 mg/kg bw (1997). MRLs (EXPRESSED AS THE SUM OF THE CONCENTRATIONS OF DIHYDROSTREPTOMYCIN AND STREPTOMYCIN): MUSCLE, LIVER AND FAT (CATTLE, SHEEP, PIGS AND CHICKENS): 0.6 m