United States Office of Pesticides and Toxic Substances
Environmental Protection Office of Pesticide Programs ITS 766C)
Agency Washington. DC 20460
&EPA Pesticide
Fact Sheet
Name Of Chemical: Ethylenethiourea (ETU)
Reason for Issuance: Initiation of Special Review
Date Issued: June 1987
Fact Sheet Number: 139
DESCRIPTION OF CHEMICAL;
Generic Name: NA
Common Name: Ethylenethiourea
Trade Names: NA
Chemical Abstracts Service (CAS) Number: 96-45-7
Year of Initial Registration: NA'
Pesticide Type: Contaminant, degradation product, and metabolite
of the EBDC pesticides.
U.S. and Foreign Producers: The principal producers of various of the
EBDC pesticides include FMC Corporation,
Pennwalt Corporation, and Rohm & Haas
Company.
USE PATTERNS AND FORMULATIONS:
ETU is a contaminant, metabolite, and degradation product of
the family of pesticides known as the EBDCs. There are
five such pesticides currently registered: mancozeb, maneb,
metiram, nabam, and zineb. All registrations of araobam products
are now cancelled. In their agricultural uses, the EBDC pesticides
are broad spectrum fungicides used to prevent crop damage by
fungi and to protect harvested crops from deterioration. Some
EBDC pesticides products are also used as industrial biocides in
some applications.
Although these pesticides are used on a wide variety of
crops, the principal crops on which they are used are apples,
potatoes, and tomatoes. All types of formulation types are
registered. Application is done by various methods, including
airblast, ground boom, and sprinkler irrigation.
-------
2
SCIENCE FINDINGS
Summary Science Statement: ETU has been classified by the Agency
as a Group 82 oncogen (probable human carcinogen). ETU has
induced an increased incidence of thyroid tumors in rats, arid
liver tumors in mice. In addition, ETU has been shown to be a
teratogen in studies with rats and hamsters, and has shown thyroid
effects in rat feeding studies.
Toxicology Characteristics
Subchroriic Toxicity:
Oral (rats): NOEL for thyroid effects (Sprague—Dawley
rats) - 5 ppm (0.25 mg/kg/day) (Freudenthal,
1977).
Oral (mouse): NOEL for liver effects — 10 ppm
NOEL for thyroid effects — 10 ppm
(1.72 mg/kg/day, males; 2.38 mg/kg/day, female)
(O’Hara & DiDonata, 1985).
Oral (monkey): NOEL for thyroid effects — < 50 ppm.
NOEL not determined for thyroid effects in the dog.
Chronic Toxicity:
Chronic Toxicity: No chronic NOEL determined for thyroid
effects in the rat. Study required in
Sprague-Dawley rats.
Oncogenicity: Potency estimate of 0.1428 mg/kg/day based on
liver tumors in mice (Innes 1969).
Produced thyroid tumors in rats (Ulland 1972;
Graham 1975).
Teratology: Teratogenic effects: NOEL (rats) — 5 mg/kg
(Khera 1973). The dose resulting in abnormalities
such as hydrocephalus in the hamster was 27
times that resulting in hydrocephalus in the
rat.
Reproduction: Study required.
Mutagenicity: Mixed results - weakly genotoxic.
-------
3
Tolerance Assessment : Tolerances have been set for maneb and
zineb at 40 CFR 180.110 arid 40 CFR 180.115, respectively.
Tolerances for inancozeb, expressed as zinc ethylene bisdithio-
carbamate, have been established for raw agricultural commodities
at 40 CFR 180.176, for meat byproducts at 40 CFR 180.319, and in
processed food and feed at 21 CFR 193.460 and 21 CFR 561.410,
respectively.
SUMMARY OF REGULATORY POSITION & RATIONALE
The Agency is initiating a Special Review of the EBDC
pesticides because of concern about the oncogeriic risk to consumers
from dietary exposure to ETtJ fro ’ foods treated with these
pesticides, and the risks of teratogenicity and adverse thyroid
effects to applicators and mixer/loaders from exposure to ETU.
ETU is present as part of the residue of the EBDC pesticides on
treated agricultural commodities. In addition, a portion of the
EBDC pesticide residues convert into ETU in the body after ingestion.
The Agency estimates that the lifetime dietary oncogenic risk to
consumers from these two sources of exposure to ETU is 2.2 x
lOs. This estimate is based on exposure to ETU from the residues
of only one of the EBDC pesticides. Consequently, the overall
dietary risk may be higher.
Applicators and mixer/loaders are exposed to ETU during
application and mixing and loading of the EBDC pesticides.
Because ETU is a contaminant, degradation product, and metabolite
of these pesticides, it is present in tank mixes and in the
formulations of the EBDC pesticides.
The Agency calculated margins of safety for teratogenic and
thyroid effects from exposure to ETU in mancozeb, one of the EBDC
pesticides. Several margins of safety were below the threshold
of concern. (A safety factor of 100 is used to measure the
acceptable margin between actual exposure and the levels at which
chronic effects may occur. A margin of safety for chronic effects
of less than 100 is unacceptable). For example, airblast
applicators applying mancozeb to apples had margins of safety
for exposure to ETU of 87 for teratogenic effects, and 11 for
thyroid effects. Ground boom applicators applying mancozeb to
potatoes, onions and tomatoes had margins of safety for exposure
to ETU of less than 100 for thyroid effects. The Agency is not
initiating a Special Review on oncogenic risks to applicators and
mixer/loaders because the relative risks and the number of persons
potentially exposed are low.
This elevated level of potential risk warrants a careful
examination during the Special Review process of the risks and
benefits of using the EBDC pesticides, and a determination
whether such uses should be cancelleil or otherwise regulated.
-------
4
Contact Person :
David Giamporcaro
Review Manager
Special Review Branch
Registration Division
Office of Pesticide Programs
(703)557—0481
------- |