A-9568 B
Overview
Chemical Names
4,6-DIAMINO-2-(CYCLOPROPYLAMINO)-5-PYRIMIDINECARBONITRILE; 4,6-DIAMINO-2-CYCLOPROPYLAMINOPYRIMIDINE-5-CARBONITRILE
Synonyms
CLIK; A-9568 B; CGA 183893
Functional Class
Veterinary Drug
INSECTICIDE
INSECTICIDE
Evaluations
Evaluation year: 2003
ADI:0-0.007 mg/kg bw
ADI:
0-0.007 mg/kg bw
Comments:
The Committee established an ADI of 0-7 mg/kg bw, on the basis of the NOEL of 0.71 mg/kg bw per day for increased plasma cholesterol in the 1-year study of toxicity in dogs and a safety factor of 100, rounded to one significant figure. Estimated intake values corresponding to the MRLs were 0.13 mg/p/d at the TMDI (31% of ADI). The EDI based on intake of residues at geometric mean sum of 2 marker compounds is 0.031 mg/p/d (7% of ADI). The EDI based on GEMS/Food consumption data at MRLs is 0.18-3.6 µg/p/d (0.04-0.85% of ADI).
MRL Comment:
MRLs (expressed as dicyclanil, in mg/kg): Muscle (sheep): 0.15; Liver and kidney (sheep): 0.125; Fat (sheep): 0.2
Intake:
TMDI: 0.13 mg/p/d (31% of ADI). Intake based on intake of residues at geometric mean sum of 2 marker compounds: 0.031 mg/p/d (7% of ADI). Intake based on GEMS/Food consumption data at MRLs: 0.18-3.6 µg/p/d (0.04-0.85% of ADI).
Meeting:
60
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
1-year dog study (Altmann, 1995): Beagles (4/sex/group) received technical-grade dicyclanil in the diet at a concentration of 0, 5, 25, 150, or 750 mg/kg of diet (0, 0.16, 0.71, 4.4, and 23 mg/kg bw/day (males) and 0, 0.15, 0.77, 5.1, and 23 mg/kg bw/day (females)). Two/sex in the control and high-dose groups were maintained for a 4-week recovery period. One high dose female was found dead on day 13. One high dose male was killed on study day 32 after vomiting, showing marked apathy, lying in a lateral position, and weight loss correlated to reduced food intake. Vomiting and decreased food consumption & bodyweight gain was observed in high dose females. Throughout the treatment period, the plasma cholesterol was increased at the high dose in both sexes and in males at 150 mg/kg. High dose males showed slightly lower plasma calcium concentrations. Both males and females at the high dose had reduced plasma bilirubin and urea and alkaline phosphatase. The absolute and relative liver weights were increased in high-dose animals, but only the change in absolute weight in males was statistically significant. The absolute (statistically significant) and relative weights of the heart were decreased in high-dose females. On the basis of increased plasma cholesterol in males, the NOEL was 25 mg/kg of diet, equal to 0.71 mg/kg bw/day .
Animal Specie:
Dog
Effect:
Increased plasma cholesterol (males)
NOEL:
0.71 mg/kg bw/d
LOEL:
4.4 mg/kg bw/d
Point of departure:
0.71 mg/kg bw/d
Previous Years:
2000, TRS 900-JECFA 54/43, FNP 41/13-JECFA 54/29, FAS 45-JECFA 54/75. 0-0.007 mg/kg bw. MRLs (EXPRESSED AS DICYCLANIL, in mg/kg): MUSCLE (SHEEP): 0.2; LIVER AND KIDNEY (SHEEP): 0.4; FAT (SHEEP): 0.15. FU. MRL.
2000, TRS 900-JECFA 54/43, FNP 41/13-JECFA 54/29, FAS 45-JECFA 54/75. 0-0.007 mg/kg bw. MRLs (EXPRESSED AS DICYCLANIL, in mg/kg): MUSCLE (SHEEP): 0.2; LIVER AND KIDNEY (SHEEP): 0.4; FAT (SHEEP): 0.15. FU. MRL.