United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
EPA-738-F-96-023
October 1996
R.E.D. FACTS
Pesticide
Reregistration
Use Profile
Chlorpropham
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered before November 1, 1984, be
reregistered to ensure that they meet today's more stringent standards.
In evaluating pesticides for reregi strati on, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
each pesticide's risks. EPA then reregisters pesticides that can be used
without posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregi strati on, EPA explains the basis
for its decision in a Reregi strati on Eligibility Decision (RED) document.
This fact sheet summarizes the information in the RED document for
reregi strati on case 0271, chlorpropham.
Chlorpropham is a herbicide and plant growth inhibitor used to
control mouseear chickweed in spinach and fruiting in ginkgo trees, reduce
Botrytis infection in Easter lilies as well as assist in their floral bud removal,
and inhibit sprouting in stored potatoes. Formulations include emulsifiable
concentrates (36%, 46.5%, and 25% active ingredient), soluble concentrates
(49.6%, 78.5%, and 78.4% active ingredient) and a ready-to-use product
(78.4% active ingredient).
Chlorpropham is applied by aerosol generator, mist blower, sprayer,
low pressure ground boom, and foaming apparatus. Use practice
limitations include the following:
• NPDES restrictions;
• a 30 day pre-harvest interval for spinach;
• prohibition of use on seed potatoes;
• prohibition of application through any type of irrigation equipment;
and
• ventilation requirements.
-------
Regulatory
History
Human Health
Assessment
Chlorpropham was registered in the United States in 1962 as a pre-
emergence and post-emergence herbicide and as a plant growth regulator.
It was originally registered for use on a variety of terrestrial food crops,
nonfood crops, and ornamentals to control broadleaf weeds and grasses,
and sprouting in stored potatoes. The Agency published an evaluation of
existing data and identified data gaps in the December 1987 Guidance for
the Reregi strati on of Pesticide Products Containing Chlorpropham as the
Active Ingredient (NTIS #PB88-169917). This Registration Standard
required additional data in the areas of product chemistry, residue
chemistry, toxicology, ecological effects, and environmental fate. By 1990,
the primary registrants had dropped all nationwide uses of Chlorpropham
except for sprout control on post-harvest stored potatoes. However, an
additional 11 registrations for use within a particular county or state
(registered under FIFRA Sect. 24(c)) remain today for use on spinach,
Easter lilies, and ginkgo trees.
A Data Call-In (DCI) was issued in April of 1994 requiring an
analytical method to detect a metabolite of Chlorpropham, 4-
hydroxychlorpropham-O-sulfonic acid, and a residue study to test for that
metabolite in meat and milk. The Agency is considering these data
confirmatory to the decisions in the RED document.
Toxicity
In studies using laboratory animals, Chlorpropham generally has been
shown to be of low acute toxicity. It is slightly toxic by the oral route and
has been placed in Toxicity Category III (the second lowest of four
categories) for this effect. Chlorpropham is a mild eye and skin irritant, and
is practically non-toxic through dermal exposure.
A 21-day dermal study using rabbits produced skin irritation and
blood cell changes in both sexes. A 60-week chronic feeding study in
beagle dogs resulted in reduced body weight gain, anemia, and changes in
thyroid function and structure. In a two-year chronic rat feeding study,
survival was not adversely affected by treatment. However, body weight
gain was reduced and there was destruction and loss of red blood cells.
Chlorpropham has been evaluated for carcinogenic activity in both
the rat and mouse. No treatment-related cancer effects were observed in the
study using mice, and the only treatment-related effects in the rat occurred
at a dose considered excessive by the Agency. The Agency has classified
Chlorpropham in Group E (evidence of non-carcinogenicity for humans)
under the Agency's cancer classification guidelines.
A developmental study in the rat produced one treatment related fetal
effect — an increased incidence of rudimentary 14th rib. A developmental
study with rabbits resulted in increased embryo resorptions and post-
implantation loss. A reproductive rat study affected growth and
-------
histopathological changes in the spleen, bone marrow, liver, and kidney.
Chlorpropham tested positive in two out of four mutagenicity studies.
Dietary Exposure
People may be exposed to residues of chlorpropham through the diet.
Currently, raw agricultural commodity tolerances for chlorpropham on
post-harvest potatoes and soybeans are listed under 40 CFR §180.181.
Also, interim tolerances for multiple crops are listed under 40 CFR
§180.319. The Agency has reassessed the tolerance on post-harvest
potatoes and determined that the tolerance value should be lowered from 50
ppm to 30 ppm.
The tolerance for soybeans and many of the interim tolerances will be
proposed for revocation because their use sites are no longer supported by
any registrant of chlorpropham. It should be noted that revoking these
tolerances may impact the importation into the United States of
corresponding food items bearing chlorpropham residues. Any interested
party who wishes to maintain a chlorpropham residue tolerance for
importation purposes in the absence of a registered use should contact the
Agency. In general, the Agency requires the same product chemistry and
toxicology data to support an import tolerance as are required to support
FIFRA registrations. The Agency also requires residue chemistry data
representative of growing conditions in the exporting countries.
EPA has assessed the dietary risk posed by chlorpropham. When risk
was estimated based on tolerance level residues of 30 ppm on potatoes, the
Anticipated Residue Concentration (ARC) for the overall U.S. population
represents 42% of the Reference Dose (RfD). The RfD is the amount
believed not to cause adverse effects if consumed daily over a 70-year
lifetime. Any exposure level less than 100% of the RfD is considered to be
an acceptable dietary risk. The most highly exposed subgroup, children 1
to 6 years of age, has an ARC which represents 85% of the RfD. Therefore,
it appears that chronic dietary risk is minimal.
Occupational and Residential Exposure
Chlorpropham is not currently registered for residential use.
Consequently, Margins of Exposure (MOEs), a ratio of the estimated
exposure level to the no observed effect level (NOEL) of 500 mg/kg/day
from a 21-day dermal study, were only calculated for occupational handlers
of chlorpropham in high exposure potential scenarios.
Human Risk Assessment
Acute dietary exposure is anticipated to be significantly lower than
2.5 mg/kg/day, which is the exposure that would trigger a concern based on
effects from the developmental rabbit study. Chronic dietary risk was
-------
assessed and exposure to the general population and all subgroups was less
than the RfD.
Although chlorpropham is classified as a group E chemical (evidence
of non-carcinogenicity for humans) according to the Agency's cancer
classification guidelines, one of its metabolites, 3-chloroaniline, is
structurally similar to a known carcinogen, 4-chloroaniline. There are no
cancer data available on 3-chloroaniline. However, the Agency believes it
is appropriate to use the cancer potency (Qj*) from 4-chloroaniline to gauge
any potential risk from 3-chloroaniline. Based on the structure of the
compounds, the Agency believes that 3-chloroaniline is probably, at most,
equally as potent and not likely to be more potent than 4-chloroaniline.
Two risk scenarios were used in the dietary cancer risk assessment.
One scenario would be more typical of the nationwide risk to chlorpropham
as this chemical is currently used. This scenario assumes that the average
public is exposed to 3-chloroaniline solely through residues on stored
potatoes.
The second scenario, termed the "local milkshed" scenario, describes
what could be a higher exposure in rural communities where cattle are fed
potato peelings. This scenario assumes that residues of 3-chloroaniline
would be present in beef liver based on a cattle diet of 75% treated potato
waste and in milk at half the limit of detection. It further assumes that these
food commodities are distributed locally.
The cancer risk assessment from the typical nationwide scenario
resulted in a risk estimate of 3 x 10"6. The resulting risk estimate from the
local milkshed assessment was 4 x 10"6. Both of these risk estimates exceed
the 1 x 10"6 estimate of individual excess lifetime cancer risk generally
considered to be negligible. However, for the reasons noted below, the
Agency believes these numbers likely represent an overestimation of risk.
(If new chlorpropham food uses are registered in the future which would
increase the dietary exposure to 3-chloroaniline, the Agency may require
additional data regarding the toxicity of 3-chloroaniline.)
• Based on a study by Amdur et al (1991), 3-chloroaniline would not be
expected to be more potent than 4-chloroaniline.
• Rat metabolism studies detected 3-chloroaniline but no 4-
chloroaniline.
• An oncogenicity study of chlorpropham in rats did produce an
increase in testicular Leydig cell adenomas. These benign tumors
were only observed at one excessive dose level (higher than the
maximum tolerated dose). Yet none of the tumor types which have
been observed in 4-chloroaniline data were present in the
chlorpropham studies (i.e, the 3-chloroaniline that was present in the
test was not observed having a similar mode-of-action effect).
-------
Environmental
Assessment
Additional Data
Required
Product Labeling
Changes
Required
The cancer dietary risk from spinach is likely to be small compared to
potatoes because of its lower consumption and lower residues. However, if
the spinach use is maintained, plant metabolism and possibly field residue
studies analyzing for 3-chloroaniline may be required.
MOEs were calculated for occupational handlers in high exposure
potential scenarios. The resulting MOEs are all greater than 100, indicating
only minimal concerns.
All data requirements for the indoor use of chlorpropham have been
fulfilled. It was not necessary to perform a risk assessment for ecological
effects for the indoor use of chlorpropham.
The three outdoor uses of chlorpropham (spinach, Easter lilies, and
ginkgo trees) were registered as Special Local Needs under FIFRA Section
24(c) and are not being supported by the primary registrants of technical
chlorpropham. In order to maintain these registrations, environmental fate
and ecological effects data will have to be submitted.
EPA is requiring additional generic residue data to confirm its
regulatory assessments and conclusions for the use of chlorpropham on
potatoes. The Agency is requiring additional studies in the areas of residue
chemistry, ecological effects, and environmental fate to maintain the
outdoor uses of chlorpropham.
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, revised Confidential Statements of
Formula (CSFs), and revised labeling for reregi strati on.
All chlorpropham end-use products must comply with EPA's current
pesticide product labeling requirements. For a comprehensive list of
labeling requirements, please see the chlorpropham RED document.
Minimum personal protective equipment (PPE) for all occupational
handlers is chemical resistant gloves. A restricted-entry interval of 12 hours
has been established for the two uses (Easter lilies and spinach) which are
within the scope of the Worker Protection Standard (WPS). PPE required
for persons who must enter areas that remain under a restricted-entry
interval includes coveralls, chemical-resistant gloves, shoes, and socks.
The Agency is requiring a respirator as PPE during application and
ventilation of stored potatoes when chlorpropham is applied as an aerosol
or through forced-air distribution.
The Agency is also establishing the following entry restriction for
uses of chlorpropham on stored potatoes when it has been applied as an
aerosol or through forced-air distribution:
"Do not enter or allow any person, other than a person equipped with
the appropriate handler personal protective equipment including a
-------
Regulatory
Conclusion
For More
Information
respirator, to enter the treated area until the area has been ventilated
for either a total of two (2) hours with fans or other mechanical
ventilation or four (4) hours with windows, vents, or other passive
ventilation or until such time as 10 complete air exchanges have
occurred. The ventilation time may be interrupted, i.e., the time may
be accumulated at sporadic intervals, such as 15 minutes of
ventilation followed by a period with no ventilation, until the total
required ventilation time has accumulated."
Chlorpropham products which are labeled for application to potatoes
on a conveyor belt must contain the following statement:
"Following application, workers (e.g. baggers) must wear chemical-
resistant gloves while potatoes are wet."
The Agency has determined that the nationwide use of chlorpropham
on stored potatoes to inhibit sprouting as currently registered will not cause
unreasonable risk to humans or the environment and this use is eligible for
reregi strati on. These products will be reregistered once the required
confirmatory generic data, product specific data, CSFs, and revised labeling
are received and accepted by EPA.
However, there are four registrations of chlorpropham on potatoes
first registered under Section 24(c) of FIFRA in the states of North Dakota,
Oregon, and Washington which have application rates not supported by
field residue data. These products are eligible for reregi strati on, provided
registrants of these products reduce their label application rates or submit
additional field residue data to the Agency which support these higher rates.
In addition, there are currently seven chlorpropham registrations first
registered under Section 24(c) of FIFRA restricted to particular states or
counties for use on spinach, Easter lilies, and ginkgo trees. There are
insufficient data to make a reregi strati on eligibility decision on these
outdoor uses of chlorpropham. The Agency is requiring additional studies
in the areas of residue chemistry, ecological effects, and environmental fate
to maintain these uses. There are sufficient data available to support the
existing interim tolerance on spinach while new data are generated.
EPA is requesting public comments on the Reregi strati on Eligibility
Decision (RED) document for chlorpropham during a 60-day time period,
as announced in a Notice of Availability published in the Federal Register.
To obtain a copy of the RED document or to submit written comments,
please contact the Pesticide Docket, Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregi strati on Information System
-------
at 703-308-7224. They also are available on the Internet on EPA's gopher
server, GOPHER.EPA.GOV, or using ftp on FTP.EPA.GOV, or using
WWW (World Wide Web) on WWW.EPA.GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489-8190, fax 513-489-8695.
Following the comment period, the chlorpropham RED document
also will be available from the National Technical Information Service
(NTIS), 5285 Port Royal Road, Springfield, VA 22161, telephone 703-487-
4650.
For more information about EPA's pesticide reregi strati on program,
the chlorpropham RED, or reregi strati on of individual products containing
chlorpropham, please contact the Special Review and Reregi strati on
Division (7508W), OPP, US EPA, Washington, DC 20460, telephone
703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
------- |