TOXICOLOGY
Fenthion was reviewed by the 1995 JMPR, which established an ADI of 0-0.007 mg/kg bw on the basis of an NOAEL of 0.07 mg/kg bw per day (the highest dose tested) for the inhibition of erythrocyte acetylcholinesterase activity in a 25-day study in volunteers. The available data did not permit the Meeting to establish an acute reference dose (acute RfD) different from the ADI. A study of neurotoxicity in rats given a single dose was available to the present Meeting to assist in reviewing the acute RfD.
In rats treated by gavage with single doses of 0, 1, 50 (males), 75 (females), 150 (males), or 225 (females) mg/kg bw of technical-grade fenthion, the NOAEL for the inhibition of brain acetylcholinesterase activity and for neurobehavioural effects was 1 mg/kg bw.
In a study that was reviewed by the 1995 JMPR, the administration of 0.07 mg/kg bw to volunteers daily for about 25 days did not inhibit erythrocyte acetylcholinesterase activity.
The Meeting concluded that an acute reference dose of 0.01 mg/kg bw could be allocated by taking into account the NOAEL of 1 mg/kg bw in rats and applying a safety factor of 100.
An addendum to the toxicological monograph was prepared.
TOXICOLOGICAL EVALUATION
RELEVANT FOR ESTABLISHING AN ACUTE RFD
Levels that cause no toxic effect
|
Rat: |
1 mg/kg bw (single oral administration, inhibition of brain acetylcholinesterase activity) |
|
| |
|
Human: |
0.07 mg/kg bw per day (four-week study in volunteers, highest dose tested) |
Estimated acute reference dose for humans
0.01 mg/kg bw
