TRYPAMIDIUM
Overview
Chemical Names
3-AMINO-8-[3-[3-(AMINOIMINOMETHYL)PHENYL]-1-TRIAZENYL]-5-ETHYL-6-PHENYLPHENANTHRIDINIUM CHLORIDE
Synonyms
SAMORIN; TRYPAMIDIUM
CAS number
34301-55-8
Functional Class
Veterinary Drug
TRYPANOCIDE
TRYPANOCIDE
Evaluations
Evaluation year: 1993
ADI:0-0.1 mg/kg bw
ADI:
0-0.1 mg/kg bw
Comments:
An ADI of 0-100 µg per kg of body-weight was established for isometamidium based on the NOAEL of 50 mg/kg bw/day in the 13-week rat study and a safety factor of 500. The Committee chose this safety factor because of the marginal pharmacological
effects seen at the lowest dose in the rat study and the limited extent of the data available, although it recognized that neither the drug nor its metabolites were bioavailable when given by the oral route.
MRL Comment:
MRLs: Muscle and fat: 0.1 mg/kg; Liver (cattle): 0.5 mg/kg; Kidney (cattle): 1 mg/kg; Milk (cattle): 0.1 mg/l
MRL Code:
MRL
Intake:
TMDI (isometamidium equivalents): 1.11 mg/p/d
Meeting:
40
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
13-week rat study (Peters et al., 1991): Crl:CD(SD)BR rats (10/sex/dose) were gavaged with 0, 50, 225 or 1000 mg/kg bw/d isometamidium in 0.5% aqueous methylcellulose for 13 weeks. Immediately after treatment, all animals showed salivation, discoloured fur, hair loss and respiratory distress, which was most severe in the two highest dose groups. 3/sex at the high dose died by week 3, all showing disturbed gait and posture, diarrhoea, emaciation, distended abdomen and irregular breathing. The remaining high dose animals were sacrificed on Week 4. Slight, significantly increased relative spleen weight was noted in 225 mg/kg males. Distended ileum was recorded in both sexes at 225 mg/kg bw while distended caecum was reported at all doses. Mild hyperplasia of the caecal mucosa with varying degrees of inflammatory cell infiltration and luminal dilation was noted in 225 mg/kg males. Apart from the acute post-dosing clinical signs, which were of pharmacological origin and caecal distension at necropsy, there were no other effects at 50 mg/kg bw/day, the non-toxic dose level in this study.
Animal Specie:
Rat
NOAEL:
50 mg/kg bw/day
Point of departure:
50 mg/kg bw/day
Previous Years:
1989, TRS 788-JECFA 34/44, FNP 41/2-JECFA 34/43, FAS 25-JECFA 34/125. NO ADI ALLOCATED. NO MRLs ALLOCATED. NO. O
1989, TRS 788-JECFA 34/44, FNP 41/2-JECFA 34/43, FAS 25-JECFA 34/125. NO ADI ALLOCATED. NO MRLs ALLOCATED. NO. O