EPA Reviewer: [Abdallah Khasawinah]{.underline}, Ph.D. , Date

Reregistration Branch [4]{.underline} (7509C)

EPA Secondary Reviewer: [Suhair Shallal, Ph.D.]{.underline} , Date

Reregistration Branch [4]{.underline} (7509C)

**TXR \# 0050281**

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  DATA EVALUATION RECORD

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[STUDY TYPE]{.underline}: Oral Study - Humans; Non-Guideline

[DP BARCODE]{.underline}: D281954 [SUBMISSION CODE]{.underline}:S609686

[P.C. CODE]{.underline}: 099801 [TOX. CHEM. NO.]{.underline}: 426A

[TEST MATERIAL (PURITY)]{.underline}: Ethephon (2.5% a.i.)

[SYNONYMS]{.underline}: 2-Chloroethyl phosphonic acid; Ethrel

[CITATION]{.underline}: Weir, R.J. (1977) Final Report: Evaluation of
Ethephon in Human Volunteers: LBI Project No. 2416. (Unpublished study
received Aug 30, 1978 under 264‑267; prepared by Litton Bionetics, Inc.,
submitted by Union Carbide Agricultural Products Co., Inc., Ambler, Pa.;
CDL:235116‑A). May 9, 1977 MRID 00066931

[SPONSOR]{.underline}: Union Carbide Agricultural Products Co., Ambler,
Pa.

[EXECUTIVE SUMMARY]{.underline}:

In a non-guideline special human study (MRID 00066931), ethephon was
administered by capsule in a powdered formulation (2.5% a.i.
weight/weight) of hydrated silica and starch to human adults (10/sex) at
an average dose of 0.5 mg a.i./kg/day or placebo 0 mg/kg/day (6 males
and 4 females) for 16 consecutive days followed by a 29 day recovery
period (phase 3). The dosing phase (phase II) was preceded with a 6 day
period (phase I) where all subjects received daily placebos.
Administration of the test material or the placebo was given orally by
capsule divided into three daily doses. Each subject received 2 capsules
postprandially for the first two dosing periods; the third dose was
given at the end of the work day in order to simulate as closely as
possible ingestion of the material as a crop residue. The capsules were
dispensed daily (5 days/week) by an assistant who observed the subjects
while they took each capsule and recorded solicited comments related to
the ingestion of the material for 8 hours. The subjects and the
assistant did not know which capsules were placebo or the test material
in of the study phases. Each Friday, the subjects received a supply of
capsules to be taken during the two day weekend. All subjects were
monitored regularly for adverse effects. Hematology measurements and
clinical chemistry were conducted on blood samples collected during
phases I, II and III while urinalysis was conducted on samples collected
during phase II. ChE (plasma and RBC) determinations were conducted
using the ΔpH/hr method (modified Michel method) on blood collected
during phases I, II, and III.

No clinical symptoms were reported. Hematological, clinical chemistry
values and urinalysis parameters were comparable to the placebo
controls.

Plasma and RBC ChE activities were significantly inhibited in both
placebo and test groups. Therefore, this finding makes any conclusions
regarding the effects attributable to ethephon administration
impossible. This is in contradiction to the study authors overall
conclusion that a daily ethephon oral dosage of 0.5 mg/kg/day produces
significant plasma ChE inhibition, which is reversible in 15 days.

The study is apparently well conducted but no conclusions can be made
regarding its classification.

**[COMPLIANCE]{.underline}:** Study predated GLP guidelines.