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; None-Guideline

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

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

[TEST MATERIAL (PURITY)]{.underline}: Ethephon (10% a.i.)

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

[CITATION]{.underline}: Reese, W.H., Jr. (1972) Final Report‑‑Phase II:
Evaluation of Ethrel in Human Volunteers: BRL Project No. 7223.
(Unpublished study received on unknown date under 4F1490; prepared by
Litton Industries, submitted by Union Carbide Agricultural Products Co.,
Ambler, Pa.; CDL:093946‑D). March 3, 1972. MRID 00036510

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

[EXECUTIVE SUMMARY]{.underline}:

In a non-guideline special human study (MRID 00036510), ethephon was
administered by capsule in a powdered formulation (10% a.i.
weight/weight) of hydrated silica and starch to human adults (5/sex) at
an average dose of 1.8 mg a.i./kg/day or placebo 0 mg/kg/day (3/sex) for
28 consecutive days. 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 during the first 8
hours. The subjects and the assistant did not know which capsules were
placebo or the test material. 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,
clinical chemistry and urinalysis were conducted initially and on Days
7, 14, 21, 28 and 2 weeks following the last administration. ChE (plasma
and RBC) determinations were conducted using the ΔpH/hr method (modified
Michel method) initially, and on Days 1, 2, 7, 14, 28 and 2 weeks after
the last administration.

The ethephon subjects, though exhibiting normal physical appearance and
behavior, developed typical symptoms of exposure to a cholinesterase
inhibitor such as diarrhea, increased urination and bowel movement. Thus
3 females and one male experienced a sudden Aonset of diarrhea@ or an
urgency of bowel movement of 1-4 days duration during the first week of
the compound administration; the one male experienced also loose stools
for 2 weeks. Another male complained of stomach cramps or gas for the
duration of the study. One subject in the ethephon group was asymptotic.
Five subjects experienced increased urgency and frequency of urination,
4 of whom experienced this symptom throughout the study. Two subjects
experienced decreased appetite while a third one (experiencing diarrhea)
experienced increased appetite during the first 2 days of the study.
None of the placebo subjects had similar complaints.

Unexpectedly, plasma and RBC ChE activities were similar or slightly
higher than initial values in the test subjects (the details of the ChE
determinations were not provided). No compound effects regarding
hematology, clinical chemistries and urinalysis were reported.

It is concluded that the daily dose of 1.8 mg/kg/day is the **LOAEL**
for the oral ingestion of ethephon in human subjects. The **NOAEL** is
\<1.8 mg/kg/day. This classified **acceptable/non-guideline**.

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