COOPERTRIX
Overview
Chemical Names
(RS)-alpha-CYANO-3-PHENOXYBENZYL (Z)-(1RS,3RS)-2-(CHLORO-3,3,3-TRIFLUOROPROPENYL)-2,2-DIMETHYLCYCLOPROPANECARBOXYLATE
Synonyms
PT-563; COOPERTRIX™; GRENADE®
Functional Class
Veterinary Drug
INSECTICIDE
INSECTICIDE
Evaluations
Evaluation year: 2004
ADI:0-0.005 mg/kg bw
ADI:
0-0.005 mg/kg bw
Comments:
The Committee evaluated cyhalothrin at its 54th meeting, which established a temporary ADI of 0–0.002mg/kg bw by applying a safety factor of 500 to the LOEL of 1 mg/kg bw/d for induction of liquid faeces in dogs in a 26-week study. The high safety factor was used to compensate for the absence of a NOEL in this study. The ADI was designated as temporary because the Committee was concerned that neurobehavioural effects had notbeen adequately investigated. The 2004 Committee meeting considered studies investigating genotoxicity and neurotoxicity with cylohathrin. The present Committee concluded that the data indicated an absence of genotoxicity for cyhalothrin and l-cyhalothrin. Comparison of the results of the studies of toxicity, including neurotoxicity, in rats with those in dogs suggested that cyhalothrin is of similar toxicity in the two species. The Committee established a new ADI of 0–0.005 mg/kg bw, based the LOEL of 1 mg/kg bw per day for dogs (also
the NOEL for rats) and a safety factor of 200. The safety factor incorporated a factor of 2 to compensate for the absence of a NOEL for dogs. An additional factor was considered appropriate because: liquid faeces is a common minor health effect in dogs, and some liquid faeces also occurred in control dogs; the LOEL was close to a NOEL; and because there was a clear NOEL for neurobehavioural effects in rats.
MRL Comment:
MRLs (expressed as cyhalothrin): Muscle and kidney (cattle, pigs, and sheep): 0.02 mg/kg; liver (cattle and pigs): 0.02 mg/kg; liver (sheep): 0.05 mg/kg; fat (cattle, pigs, and sheep): 0.4 mg/kg; milk (cattle): 0.03 mg/kg
Meeting:
62
Report:
Tox Monograph:
Residues:
Toxicological study
Pivotal Study:
Nonstandard neurotoxicity study in rats (Righi & Palermo-Neto, 2003): Adult male rats were given oral doses of cyhalothrin at 0, 1.0, 3.0 or 7.0 mg/kg bw for 7 days. Positive controls were treated with picrotoxin, an anxiogenic substance that is a non-competitive GABA receptor antagonist. Signs of intoxication included salivation, tremors and liquid faeces. Reduced total locomotor activity in the open field, reduced proportion of time spent in open field central zones, increased immobility time in the open field, reduced proportion of time spent exploring plus-maze open arms, and reduced time spent in social interaction were noted beginning at 3mg/kg bw/d. Serum corticosterone concentration was also increased at 3mg/kg bw/d. The NOEL was 1.0mg/kg bw/d.
26-week GLP-compliant dog study (Chesterman et al., 1981): Beagles (n=6/sex/group) were given cyhalothrin dissolved in corn oil inside a gelatin capsule at a dose of 0, 1.0, 2.5, or 10 mg/kg bw/d. Dose-related increases in the incidence of liquid faeces affected all treated groups. At 10 mg/kg bw/d, clinical signs included vomiting, salivation, incoordination, unsteadiness, collapse, muscular spasms, and convulsions. No NOEL was identified in this study owing to the finding of an increased frequency of liquid faeces at all doses. The LOEL was 1.0 mg/kg bw/ d.
Animal Specie:
Dog & rat
Effect:
Liquid feces (dogs); reduced proportion of time spent in open field central zones, increased immobility time in the open field, reduced proportion of time spent exploring plus-maze open arms, and reduced time spent in social interaction (rats)
NOEL:
1.0 mg/kg bw/ d (rats)
LOEL:
1.0 mg/kg bw/ d (dogs)
Point of departure:
1 mg/kg bw/d (LOEL for dogs; NOEL for rats)
Previous Years:
2002, TRS 911-JECFA 58/36, FNP 41/13-JECFA 54/1 (2000), FAS 45-JECFA 54/41 (2000). 0-0.002 mg/kg bw (TEMPORARY). THE COMMITTEE EXTENDED THE TEMPORARY ADI THAT WAS ESTABLISHED AT THE FIFTY-FOURTH MEETING (2000), PENDING THE RESULTS OF STUDIES APPROPRIATE F
2002, TRS 911-JECFA 58/36, FNP 41/13-JECFA 54/1 (2000), FAS 45-JECFA 54/41 (2000). 0-0.002 mg/kg bw (TEMPORARY). THE COMMITTEE EXTENDED THE TEMPORARY ADI THAT WAS ESTABLISHED AT THE FIFTY-FOURTH MEETING (2000), PENDING THE RESULTS OF STUDIES APPROPRIATE F