Application for the Reassessment of a Hazardous Substance under ...

1984). QA study. Study conducted according to US EPA PesticideAssessment Guidelines, Subdivision F, Hazard Evaluation: Human andDomestic Animals, Addendum 10: Neurotoxicity Series 81, 82 and 83,dated March 1991.―Materials and Methods―Dichlorvos (AMVAC Chemical Corporation, Los Angeles, CA, USA; lotNo. 802097; 97.87% purity) was administered orally by gavage to 12 adultfemale domestic hens per group (approximately 12-months old; 1945-2295g bw; Atkinson Bros, Postland, Crowland, Peterborough, Cambridgeshire,England) at 0, 0.3, 1.0 or 3.0 mg/kg bw/d[ay] in distilled water for 28 days.An additional group of 3 birds was administered 0.1 mg/kg bw/d[ay]dichlorvos for measurement of brain ChE activity. A positive control groupwas administered a daily oral gavage dose of 7.5 mg/kg bw/d[ay] TOCP(Coalite Chemical Group, location unspecified; Batch No. S16848; assumed100% purity) in corn oil for 28 days.―Results“Mortalities, clinical signs: One bird from the 1.0 mg/kg bw/d[ay] groupand 4 birds from the 3.0 mg/kg bw/d[ay] group died during or immediatelyafter the 28-day dosing period. Pretreatment mortalities in other groups(including the control) were due to aggression. Treatment-related clinicalsigns were observed at 1.0 and 3.0 mg/kg bw/d[ay] dichlorvos, but did notoccur in any other groups (including the positive control). At 1.0 mg/kgbw/d[ay], only 2/21 birds exhibited clinical signs, which included aninability to stand and unsteadiness. At 3.0 mg/kg bw/d[ay], 19/21 birds werequiet or subdued and unsteady. These clinical signs were observed 30 minafter dosing and were reported to last for up to 8 hours. By day 30, allsurviving birds appeared normal.“Delayed locomotor ataxia: It was reported that there were no clinical signsof neurotoxicity and no evidence of delayed locomotor ataxia in any bird.However, the results of the assessment of ataxia were not provided,including results for the positive control.“Brain ChE activity: There was dose-related inhibition of brain ChEactivity, which was toxicologically significant (ie. >20% relative to thecontrol) at and above 1.0 mg/kg bw/d[ay] at day 4, and at and above 0.3mg/kg bw/d at day 30. No statistical analysis was performed on this data.“NTE activity: There was no treatment-related effect on either brain orspinal cord NTE activity. [Neuropathy target esterase (NTE); Inhibition ofthis particular enzyme is a marker for predicting delayed neurotoxicity fromorganophosphate pesticides. (Handbook of Pesticide Toxicology, Ed RKrieger, 2001, Academic Press, San Diego CA. USA, Vol 2 p953ff.)] Incontrast, the positive control (7.5 mg/kg bw/d[ay] TOCP) caused a markedreduction in both brain and spinal cord NTE activity relative to the negativecontrol at day 4 and 30. No statistical analysis was performed on this data.Dichlorvos reassessment – application Page 247 of 436