United States
Environmental Protection
Agency
Health Effects Support
Document for S-Ethyl
dipropylthiocarbamate (EPTC)
-------
-------
Health Effects Support Document
for
S-Ethyl dipropylthiocarbamate (EPTC)
U.S. Environmental Protection Agency
Office of Water (43 04T)
Health and Ecological Criteria Division
Washington, DC 20460
www.epa.gov/safewater/ccl/pdf/EPTC.pdf
EPA Document Number: 822-R-08-006
January, 2008
Printed on Recycled Paper
-------
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 IV
-------
FOREWORD
The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator
of the Environmental Protection Agency (EPA) to establish a list of contaminants to aid the
Agency in regulatory priority setting for the drinking water program. In addition, the SDWA
requires EPA to make regulatory determinations for no fewer than five contaminants by August
2001 and every five years thereafter. The criteria used to determine whether or not to regulate a
chemical on the Contaminant Candidate List (CCL) are the following:
The contaminant may have an adverse effect on the health of persons.
• The contaminant is known to occur or there is a substantial likelihood that the
contaminant will occur in public water systems with a frequency and at levels of
public health concern.
• In the sole judgment of the Administrator, regulation of such contaminant presents a
meaningful opportunity for health risk reduction for persons served by public water
systems.
The Agency's findings for all three criteria are used in making a determination to
regulate a contaminant. The Agency may determine that there is no need for regulation when a
contaminant fails to meet one of the criteria. The decision not to regulate is considered a final
Agency action and is subject to judicial review.
This document provides the health effects basis for the regulatory determination for
s-ethyl dipropylthiocarbamate (EPTC). In arriving at the regulatory determination, The Office
of Water used the Re-registration Eligibility Document (RED) for EPTC published by the Office
of Pesticides Programs (OPP), as well as any OPP health assessment documents that supported
the RED. The following publications from OPP were used in development of this document.
U.S. EPA (United States Environmental Protection Agency). 1999. Reregi strati on
eligibility decision. EPTC. EPA 738-R-99-006. Washington, DC: U.S. EPA Office of
Prevention, Pesticides and Toxic Substances.
U.S. EPA (United States Environmental Protection Agency). 1987. S-Ethyl
dipropylthiocarbamate (EPTC) Integrated Risk Information System. Office of Research
and Development. Washington DC.
Information from the OPP risk assessment was supplemented with information from the
primary references for key studies where they have been published and recent studies of EPTC
identified in a literature search conducted in 2004 and updated in 2007.
A Reference Dose (RfD) is provided as the assessment of long-term toxic effects other
than carcinogenicity. RfD determination assumes that thresholds exist for certain toxic effects,
such as cellular necrosis, significant body or organ weight changes, blood disorders, etc. It is
expressed in terms of milligrams per kilogram per day (mg/kg-day). In general, the RfD is an
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
-------
estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the
human population (including sensitive subgroups) that is likely to be without an appreciable risk
of deleterious effects during a lifetime.
The carcinogenicity assessment for EPTC includes a formal hazard identification and an
estimate of tumorigenic potency when available. Hazard identification is a weight-of-evidence
judgment of the likelihood that the agent is a human carcinogen via the oral route and of the
conditions under which the carcinogenic effects may be expressed.
Development of these hazard identification and dose-response assessments for EPTC has
followed the general guidelines for risk assessment as set forth by the National Research Council
(1983). EPA guidelines that were used in the development of this assessment may include the
following: Guidelines for the Health Risk Assessment of Chemical Mixtures (U.S. EPA, 1986a),
Guidelines for Mutagenicity Risk Assessment (U.S. EPA, 1986b), Guidelines for Developmental
Toxicity Risk Assessment (U.S. EPA, 1991), Guidelines for Reproductive Toxicity Risk
Assessment (U.S. EPA, 1996a), Guidelines for Neurotoxicity Risk Assessment (U.S. EPA,
1998a), Guidelines for Carcinogen Assessment (U.S. EPA, 2005), Recommendations for and
Documentation of Biological Values for Use in Risk Assessment (U.S. EPA, 1988), (proposed)
Interim Policy for Particle Size and Limit Concentration Issues in Inhalation Toxicity (U.S.
EPA, 1994a), Methods for Derivation of Inhalation Reference Concentrations and Application of
Inhalation Dosimetry (U.S. EPA, 1994b), Use of the Benchmark Dose Approach in Health Risk
Assessment (U.S. EPA, 1995), Science Policy Council Handbook: Peer Review (U.S. EPA,
1998b, 2000a), Science Policy Council Handbook: Risk Characterization (U.S. EPA, 2000b),
Benchmark Dose Technical Guidance Document (U.S. EPA, 2000c), Supplementary Guidance
for Conducting Health Risk Assessment of Chemical Mixtures (U.S. EPA, 2000d), and^4 Review
of the Reference Dose and Reference Concentration Processes (U.S. EPA, 2002a).
The chapter on occurrence and exposure to EPTC through potable water was developed
by the Office of Ground Water and Drinking Water. It is based primarily on first Unregulated
Contaminant Monitoring Rule (UCMR1) data collected under the SDWA. The UCMR1 data are
supplemented with ambient water data, as well as data from the States, and published papers on
occurrence in drinking water.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 VI
-------
ACKNOWLEDGMENT
This document was prepared under the U.S. EPA contract No. 68-C-02-009, Work
Assignment No. 2-54 and 3-54 with ICF Consulting, Fairfax, VA. The Lead U.S. EPA Scientist
is Steven Kueberuwa, Health and Ecological Criteria Division, Office of Science and
Technology, Office of Water.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 Vll
-------
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 Vlll
-------
TABLE OF CONTENTS
FOREWORD v
ACKNOWLEDGMENT vii
LIST OF TABLES xi
LIST OF FIGURES xiii
1.0 EXECUTIVE SUMMARY 1-1
2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES 2-1
3.0 USES AND ENVIRONMENTAL FATE 3-1
3.1 Production and Use 3-1
3.2 Environmental Release 3-1
3.3 Environmental Fate 3-2
3.4 Summary 3-3
4.0 EXPOSURE FROM DRINKING WATER 4-1
4.1 Introduction 4-1
4.2 Ambient Occurrence 4-1
4.2.1 Data Sources and Methods 4-1
4.2.2 Results 4-3
4.3 Drinking Water Occurrence 4-4
4.3.1 Data Sources, Data Quality, and Analytical Methods 4-4
4.3.2 CCL Health Reference Level 4-5
4.3.3 Results 4-5
4.4 Summary 4-8
5.0 EXPOSURE FROM MEDIA OTHER THAN WATER 5-1
5.1 Exposure from Food 5-1
5.1.1 Concentration in Non-Fish Food Items 5-1
5.1.2 Concentrations in Fish and Shellfish 5-1
5.1.3 Intake of EPTC from Food 5-1
5.2 Exposure from Air 5-1
5.2.1 Concentration of EPTC in Air 5-1
5.2.2 Intake of EPTC from Air 5-1
5.3 Exposure from Soil 5-2
5.3.1 Concentration of EPTC in Soil 5-2
5.3.2 Intake of EPTC from Soil 5-2
5.4 Other Residential Exposures 5-2
5.5 Occupational Exposures 5-2
5.5.1 Description of Industries and Workplaces 5-2
5.5.2 Types of Exposure 5-3
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 IX
-------
5.6 Summary 5-3
6.0 HAZARD AND DOSE-RESPONSE ASSESSMENT 6-1
6.1 Characterization of Hazard 6-1
6.1.1 Synthesis and Evaluation of Major Noncancer Effects 6-1
6.1.2 Synthesis and Evaluation of Carcinogenic Effects 6-2
6.1.3 Mode of Action and Implications in Cancer Assessment 6-3
6.1.4 Weight of Evidence Evaluation for Carcinogenicity 6-3
6.1.5 Potentially Sensitive Populations 6-3
6.2 Reference Dose 6-4
6.2.1 Choice of Principle Study and Critical Effect 6-4
6.2.2 Dose-response Characterization (dose conversion if needed) 6-4
6.2.3 Method of Analysis 6-4
6.2.4 Application of Uncertainty Factor(s) and Modifying Factor(s) 6-4
6.3 Carcinogen Assessment 6-5
6.4 Sensitive Population Considerations 6-5
6.5 Post Re-registration Health Effects Publications 6-5
6.6 CCL Health Reference Level 6-5
7.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK FROM
DRINKING WATER 7-1
7.1 Regulatory Determination for Chemicals on the CCL 7-1
7.1.1 Criteria for Regulatory Determination 7-1
7.1.2 National Drinking Water Advisory Council Recommendations 7-2
7.2 Health Effects 7-2
7.2.1 Health Criterion Conclusion 7-2
7.2.2 Hazard Characterization and Mode of Action Implications 7-3
7.2.3 Dose-Response Characterization and Implications in Risk Assessment
7-4
7.3 Occurrence in Public Water Systems 7-4
7.3.1 Occurrence Criterion Conclusion 7-5
7.3.2 Monitoring Data 7-5
7.3.3 Use and Fate Data 7-6
7.4 Risk Reduction 7-6
7.4.1 Risk Criterion Conclusion 7-7
7.4.2 Exposed Population Estimates 7-7
7.4.3 Relative Source Contribution 7-7
7.4.4 Sensitive Populations 7-7
7.5 Regulatory Determination Decision 7-8
8.0 REFERENCES 8-1
APPENDIX A: Abbreviations and Acronyms Appendix A-l
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
-------
LIST OF TABLES
Table 2-1 Chemical and Physical Properties of S-Ethyl dipropylthiocarbamate 2-2
Table 3-1 Environmental releases (in pounds) of EPTC in the United States, 1995-2002
3-2
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of EPTC in
Ambient Surface Water, 1992-2001 4-3
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of EPTC in
Ambient Ground Water, 1992-2001 4-4
Table 4-3 Summary UCMR1 Occurrence Statistics for EPTC in Small Systems (Based on
Statistically Representative National Sample of Small Systems) 4-6
Table 4-4 Summary UCMR1 Occurrence Statistics for EPTC in Large Systems (Based on
the Census of Large Systems) 4-7
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
XI
-------
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 Xll
-------
LIST OF FIGURES
Figure 2-1 Chemical Structure of S-Ethyl dipropylthiocarbamate 2-1
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 Xlll
-------
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 XIV
-------
1.0 EXECUTIVE SUMMARY
The U.S. Environmental Protection Agency (EPA) has prepared this Health Effects
Support Document for S-ethyl dipropylthiocarbamate (EPTC) to support a determination
regarding whether to regulate EPTC with a National Primary Drinking Water Regulation
(NPDWR). The available data on occurrence, exposure, and other risk considerations suggest
that, because EPTC does not occur in public water systems at frequencies and levels of public
health concern, regulating EPTC will not present a meaningful opportunity to reduce health risk.
EPA will present a determination and further analysis in the Federal Register Notice covering
the CCL proposals.
EPTC (Chemical Abstracts Services Registry Number 759-94-4) is a thiocarbamate used
to control the growth of germinating annual weeds such as broadleaves, grasses, and sedges. It
is a light yellowish, non-corrosive liquid with an aromatic odor. EPTC is released primarily into
the environment through spraying and, at times, through irrigation methods. EPTC is listed as a
Toxic Release Inventory (TRI) chemical, with air emissions constituting the majority of on-site
releases.
The primary route of exposure to EPTC is through the ingestion of residues of the
herbicide in food and drinking water. Dermal and inhalation exposure may occur in
occupational or residential settings during handling activities such as mixing, loading, or
applying.
EPTC is a reversible cholinesterase (ChE) inhibitor. In acute toxicity studies, EPTC is
moderately toxic via oral and dermal routes but displays higher toxicity when inhaled. Similar
to other thiocarbamates, EPTC does not produce a consistent ChE inhibition profile. There were
no consistent patterns observed in any of the toxicity studies with regard to species, duration of
treatment, or type of ChE enzyme measured. An increase in the incidence and severity of
cardiomyopathy was observed in subchronic and chronic studies performed in both rats and
dogs. The central and peripheral nervous systems also are affected by EPTC exposure with rats
and dogs exhibiting an increase in the incidence and severity of degenerative effects (neuronal
and/or necrotic degeneration).
In addition to its neurotoxic effects, EPTC has the ability to induce maternal and
reproductive toxicity and secondary developmental toxicity in exposed rats and rabbits. In a rat
developmental toxicity study, as well as a rabbit developmental toxicity study, toxicity
indications (decreased fetal body weight and litter size for rats; decreased fetal body weight for
rabbits) were observed, but were considered secondary to observed marked maternal toxicity
(increased mortality and decreased body weight for rats; decreased body weight and increased
mortality for rabbits). In a two-generation reproduction study in rats, effects in the offspring
were observed only at or above treatment levels that resulted in parental toxicity.
The available data for EPTC production and environmental releases all show a downward
trend. Drinking water monitoring of EPTC was conducted under the first Unregulated
Contaminant Monitoring Rule (UCMR 1) program. As a List 1 contaminant, EPTC was
monitored by all large community water systems (CWSs), large non-transient non-community
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 1-1
-------
water systems (NTNCWSs) and a statistically representative sample of small CWSs and
NTNCWSs. There were no detections of EPTC found in any of the large (i.e., serving more than
10,000 people) CWSs and large NTNCWSs. There were no detections of EPTC found in the
statistically representative national sample of 800 small (i.e., serving 10,000 people or fewer)
CWSs and NTNCWSs.
The Agency used long-term studies in mice and rats and short-term studies of
mutagenicity to evaluate the potential for carcinogenicity. Based on these data and using EPA's
2005 Guidelines for Carcinogen Risk Assessment, EPTC is not likely to be carcinogenic to
humans. Based on a 2-generation feeding study in rats, the oral Reference Dose (RfD) was
determined to be 0.025 mg/kg/day. The CCL health reference level (HRL) is 0.175 mg/L and
was derived from the RfD.
It appears that the general population is not exposed to EPTC through water consumption
or use. Therefore, the impact of regulating EPTC concentrations in drinking water on health risk
reduction is likely to be small. Regulation of EPTC in public water systems does not appear to
present a meaningful opportunity for health risk reduction.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 1 -2
-------
2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES
S-Ethyl dipropylthiocarbamate (EPIC) is a light yellowish, non-corrosive liquid with an
aromatic odor. It is highly volatile (vapor pressure 1.60 x 10"2 mm Hg at 20°C). The compound
is soluble in water (370 mg/L at 20°C) and miscible with some common organic solvents such as
acetone, ethanol, isopropanol, benzene, xylene, and kerosene. EPTC is also miscible with
hydrogen sulfide. The compound is hydrolyzed when heated in the presence of strong acids
(HSDB, 2004).
The technical grade purity of EPTC is 98.5%. Formulated products of the chemical
include granular formulations containing up to 25% active ingredient, and emulsifiable
concentrate liquids containing up to 87.8% active ingredient (U.S. EPA, 1999). Sometimes,
EPTC is supplied in a mixture with N,N-diallyl-2,2-dichloroacetamide, which is supposed to be
less toxic to maize, one of the crops to which this compound is applied (HSDB, 2004).
Figure 2-1 Chemical Structure of S-Ethyl dipropylthiocarbamate
Source: Chemfinder.com (2004)
The chemical structure of EPTC is shown above (Figure 2-1). Its physical and chemical
properties, and other reference information are listed in Table 2-1.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 2-1
-------
Table 2-1 Chemical and Physical Properties of S-Ethyl dipropylthiocarbamate
Property
Chemical Abstracts Registry
(CAS) No.
EPA Pesticide Chemical Code
Synonyms
Registered Trade Name(s)
Chemical Formula
Molecular Weight
Physical State
Boiling Point
Melting Point
Density (at 20°C)
Vapor Pressure:
At 20°C
At 25°C
Partition Coefficients:
Log Kow
LogKoc
Solubility in:
Water
Other Solvents
Conversion Factors
(at 25°C, 1 atm)
Information
759-94-4
041401
EPTC
Ethyl N,N-
dipropylthiocarbamate
Dipropylcarbamothioic acid
S-ethyl ester
EPTAM; Eradicane
C9H19NOS
189.32
Light yellow liquid
127°C
No data
0.9633 g/mL (at 25°C)
1.60xlO-2mmHg
2.4xlO-2mmHg
2.2 xlO3 ±0.1xl03at25°C
2.23-2.58
370 mg/L at 20°C
344 ± 5 mg/L at 25°C
Acetone, Ethanol,
Isopropanol, Benzene,
Xylene, Kerosene, Hydrogen
sulfide
1 ppm= 7.743 mg/m3
Img/m3 = 0.1291ppm
Source(s): U.S. EPA (1999); HSDB (2004)
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
2-2
-------
3.0 USES AND ENVIRONMENTAL FATE
3.1 Production and Use
EPTC is a pre-emergence or early post-emergence herbicide used to control the growth
of germinating annual weeds such as broadleaves, grasses, and sedges. It is used in every region
of the United States in the production of a variety of food crops. The major usage, in terms of
total pounds of active ingredient, is for crops like corn, potatoes, dry beans and peas, alfalfa, and
snap beans (U.S. EPA, 1999). The herbicide is also used on non-food plants such as trees,
shrubs, and ornamentals. In addition, EPTC is used at residential and public sites such as parks,
gardens, and golf course sand traps (HSDB, 2004).
Based on available pesticide survey usage information for the years of 1987 through
1996, an annual estimate of EPTC total domestic usage averaged approximately 20 million
pounds for almost 6 million acres treated throughout the United States (U.S. EPA, 1999).
EPTC can be synthesized by reacting ethyl mercaptan with phosgene to produce ethyl
chlorothioformate, which subsequently is reacted with di-n-propylamine. Another method for
production of EPTC is by reacting ethanethiol and dipropylcarbamoyl chloride (HSDB, 2004).
3.2 Environmental Release
EPTC is released primarily into the environment through pesticide spraying operations.
EPTC is expected to volatilize from the soil and exist primarily in the vapor phase in the air,
where it can redeposit onto earth through wet deposition (e.g., rain). Studies of rainwater have
indicated the presence of EPTC. Moderate soil affinity allows EPTC to travel moderately,
allowing some leaching to occur (HSDB, 2004).
The primary route of exposure to EPTC is through the ingestion of residues of the
herbicide in food and drinking water. Dermal and inhalation exposure may occur in
occupational or residential settings during handling activities such as mixing, loading, or
applying. Post-application exposure to EPTC during harvesting is unlikely as EPTC is normally
sprayed well before harvest time and is quickly volatilized from the soil.
Toxic Release Inventory (TRI) data for EPTC (see Table 3-1) are reported for the years
1995 to 2002 (U.S. EPA, 2004a). Total reported EPTC releases fluctuated widely in the range of
thousands of pounds per year during this period. On-site releases were dominated by air
emissions and sometimes underground injections. On-site surface water releases did not exceed
300 pounds per year; no land releases were reported. Off-site releases were significant, but
declined steadily after 1998.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 3-1
-------
Table 3-1 Environmental releases (in pounds) of EPTC in the United States, 1995-2002
Year
2002
2001
2000
1999
1998
1997
1996
1995
On-Site Releases
Air
Emissions
1,917
2,034
2,034
2,574
2,008
2,208
7,325
2,363
Surface Water
Discharges
98
99
95
156
115
113
2
291
Underground
Injection
0
1,146
6,083
903
2,088
9,501
29
373
Releases
to Land
0
0
0
0
0
0
0
0
Off-Site
Releases
708
1,655
2,798
3,570
4,565
2,778
590
9,366
Total On- &
Off-site
Releases
2,723
4,934
11,010
7,203
8,776
14,600
7,946
12,393
Source: U.S. EPA (2004a)
3.3 Environmental Fate
Direct releases of EPTC to the environment are expected due to its application as an
herbicide. The most important dissipation pathways for EPTC in the environment stem from
microbial degradation in the soil and volatilization, which can occur concurrently, making it
difficult to distinguish the primary environmental fate of the chemical. However, based on a
vapor pressure of 1.60 x 10"2mm Hg at 20°C, a Henry's Law constant of ~1 x 10"5 atm-m3/g-mol
at 25°C, and a water solubility of 375 mg/L, EPTC is likely to quickly volatilize from moist soil
after application and predominantly remain in the vapor phase while in the atmosphere. Limited
data suggest that degradation of EPTC vapor in the atmosphere occurs rapidly through reaction
with photochemically produced hydroxyl radicals (estimated half-life of 14 hours). EPTC vapor
may be removed from the atmosphere through wet deposition as indicated by the presence of
EPTC in rainwater samples (U.S. EPA, 1999).
EPTC is not expected to be rapidly incorporated into the soil with a fairly moderate log
octanol/water coefficient of 3.21 (Hansch et al., 1995). Laboratory test results inadequately
determine the relative rates of metabolism and volatilization from soils (U.S. EPA, 1999).
Data indicate that abiotic hydrolysis and direct photolysis and photo degradation are not
significant degradation pathways for EPTC in soil or water although microbial breakdown is a
significant soil removal process (HSDB, 2004). While some studies indicate that EPTC is
degraded microbially in water, there is not enough evidence to confirm this.
Based on data from terrestrial field studies, which indicate a range of dissipation half-
lives between 2 and 18.8 days, EPTC is not considered an environmentally persistent chemical.
Laboratory tests to measure dissipation rates indicate half-lives in the range of 36-75 days (U.S.
EPA, 1999). The contribution of volatilization to these dissipation rates has yet to be
determined. However, data indicate that volatilization significantly contributes to dissipation
within the first few days following application (U.S. EPA, 1999). Volatilization significantly
increases if EPTC is applied to moist surfaces, having an observed half-life of 3.4 hours under
these conditions (Nash, 1983). Studies using loam soil (25°C) inoculated with microbes proven
to degrade EPTC demonstrated an almost complete removal of EPTC from the soil within 15
days. A comparison to a sterile sample indicates that 45% of the loss was due to biodegradation
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
3-2
-------
and 55% was attributed to volatilization (Nagy et al., 1987). The biodegradation half-life of
EPIC (at a concentration of 5 ppm) in Regina heavy clay soil (pH 7.5) and Weyburn loam (pH
7.0) at 25°C was 4-5 wks and 4 wks, respectively (Smith and Fitzpatrick, 1971). Soil
biodegradation studies suggest that EPTC is, somewhat, more persistent under anaerobic
conditions with half-lives of 31 to 127 days (U.S. EPA, 1999).
The primary (soil/water) degradates of EPTC are EPTC-sulfoxide and dipropylamine.
EPTC-sulfone, N, N-dipropylformamide, dipropylamine, and ethanesulfonic acid also were
identified as degradates in one improperly conducted study which used black light; black light
does not represent sunlight (U.S. EPA, 1999). The limited data available suggest that EPTC
degradates are less persistent than their parent compound. In one study of aerobic soil
metabolism of EPTC, EPTC-sulfoxide was found to be <6% of applied EPTC (U.S. EPA, 1999).
Since EPTC has a moderate affinity for soil with a high potential for mobility in soil and
a moderate solubility in water, it may leach into groundwater (HSDB, 2004). However, due to
its low persistence, based on its short half-life and high volatility in soil, the potential for
leaching is significantly reduced. In unaged leaching columns, 9 percent of applied EPTC was
found in leachate of loam and clay loam soils, and 55 and 78 percent were found in leachate for
loamy sand and sandy loam soils, respectively. In aged soil columns, an average of 22% of the
parent was detected in the leachate. Less than 0.01 percent of applied radiolabeled (14C) found in
the leachate was attributed to degradates (U.S. EPA, 1999). Ground-water monitoring studies
indicate few occurrences of EPTC at concentrations greater than detection limits and in general,
concentrations are lower than those detected in surface waters. These data support the
conclusion that significant concentrations of EPTC will not reach groundwater (U.S. EPA,
1999).
In aqueous systems, EPTC may adsorb to suspended solids and sediment; however, it
does not have the highest affinity for carbon rich species as evident with its moderate Koc.
Accordingly, it is unlikely that EPTC will accumulate to a high level in subaqueous sediments of
ambient surface waters. Abiotic degradation, such as hydrolysis, is not expected in aqueous
systems. Biodegradation and volatilization of EPTC are expected to occur in water through
similar processes as it does in soil. Based on estimations from its Henry's Law constant and
vapor pressure, the calculated half-lives for a model river and model lake are 3 and 28 days,
respectively (HSDB, 2004).
The bioaccumulation and elimination of 14C-EPTC by bluegill sunfish were investigated
in a dynamic flow-through system, where the fish were exposed for 28 days at 22°C, followed by
depuration in EPTC free water for 14 days. Estimated bioconcentration factors for EPTC were
37, 60, and 110, respectively, in the edible, whole fish, and non-edible fish tissues. According to
a classification scheme, the whole-fish bioaccumulation factor (BCF) value suggests the
potential for bioconcentration in aquatic organisms is moderate (U.S. EPA, 1999).
3.4 Summary
Despite widespread use, the limited available data indicate that EPTC does not persist in
the environment due to rapid dissipation rates. EPTC is highly volatile. Terrestrial field studies
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 3-3
-------
indicate a range of dissipation half-lives between 2 and 18.8 days while laboratory tests to
measure dissipation rates indicated half-lives in the range of 36-75 days (U.S. EPA, 1999). The
risk of exposure to EPIC through food or groundwater is minimal due to its rapid rate of
dissipation and normally early (pre-emergent) plant application. However, estimated
bioconcentration rates in aquatic organisms are moderate, assuming the chemical persists long
enough to be taken up by an organism (U.S. EPA, 1999).
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 3-4
-------
4.0 EXPOSURE FROM DRINKING WATER
4.1 Introduction
EPA used data from several sources to evaluate the potential for occurrence of EPTC in
Public Water Systems (PWSs). The primary source of drinking water occurrence data for EPTC
was the UCMR1 program. The Agency also evaluated ambient water quality data from the
United States Geological Survey (USGS).
4.2 Ambient Occurrence
4.2.1 Data Sources and Methods
USGS instituted the National Water Quality Assessment (NAWQA) program in 1991 to
examine ambient water quality status and trends in the United States. NAWQA is designed to
apply nationally consistent analytical methods to provide a consistent basis for comparisons
among study basins across the country and over time. These occurrence assessments serve to
facilitate interpretation of natural and anthropogenic factors affecting national water quality. For
more detailed information on the NAWQA program design and implementation, please refer to
Leahy and Thompson (1994) and Hamilton and colleagues (2004).
Study Unit Monitoring
The NAWQA program conducts monitoring and water quality assessments in significant
watersheds and aquifers referred to as "study units." NAWQA's sampling approach is not
"statistically" designed (i.e., it does not involve random sampling), but it provides a
representative view of the nation's waters in its coverage and scope. Together, the 51 study
units monitored between 1991 and 2001 include the aquifers and watersheds that supply more
than 60% of the nation's drinking water and water used for agriculture and industry (NRC,
2002). NAWQA monitors the occurrence of chemicals such as pesticides, nutrients, volatile
organic compounds (VOCs), trace elements, and radionuclides, and the condition of aquatic
habitats and fish, insects, and algal communities (Hamilton et al., 2004).
Monitoring of study units occurs in stages. Between 1991 and 2001, approximately one-
third of the study units at a time were studied intensively for a period of three to five years,
alternating with a period of less intensive research and monitoring that lasted between five and
seven years. Thus, all participating study units rotated through intensive assessment in a ten-
year cycle (Leahy and Thompson, 1994). The first ten-year cycle was called "Cycle 1."
Summary reports are available for the 51 study units that underwent intensive monitoring in
Cycle 1 (USGS, 2001). Cycle 2 monitoring is scheduled to proceed in 42 study units from 2002
to 2012 (Hamilton et al., 2004).
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 4-1
-------
Pesticide National Synthesis
Through a series of National Synthesis efforts, the USGS NAWQA program is preparing
comprehensive analyses of data on topics of particular concern. These data are aggregated from
the individual study units and other sources to provide a national overview.
The Pesticide National Synthesis began in 1991. Results from the most recent USGS
Pesticide National Synthesis analysis, based on complete Cycle 1 (1991-2001) data from
NAWQA study units, are posted on the NAWQA Pesticide National Synthesis website (Martin
et al., 2003; Kolpin and Martin, 2003; Nowell, 2003; Nowell and Capel, 2003). USGS considers
these results to be provisional. Data for surface water, ground water, bed sediment, and biota are
presented separately, and results in each category are subdivided by land use category. Land use
categories include agricultural, urban, mixed (deeper aquifers of regional extent in the case of
ground water), and undeveloped. The National Synthesis analysis for pesticides is a first step
toward the USGS goal of describing the occurrence of pesticides in relation to different land use
and land management patterns, and developing a deeper understanding of the relationship
between spatial occurrence of contaminants and their fate, transport, persistence, and mobility
characteristics.
The surface water summary data presented by USGS in the Pesticide National Synthesis
(Martin et al., 2003) only include stream data. Sampling data from a single one-year period,
generally the year with the most complete data, were used to represent each stream site. Sites
with few data or significant gaps were excluded from the analysis. NAWQA stream sites were
sampled repeatedly throughout the year to capture and characterize seasonal and hydrologic
variability. In the National Synthesis analysis, the data were time-weighted to provide an
estimate of the annual frequency of detection and occurrence at a given concentration.
The USGS Pesticide National Synthesis only analyzed ground water data from wells;
data from springs, and agricultural tile drains were not included. The sampling regimen used for
wells was different than that for surface water. In the National Synthesis analysis (Kolpin and
Martin, 2003), USGS uses a single sample to represent each well, generally the earliest sample
with complete data for the full suite of analytes.
NAWQA monitored bed sediment and fish tissue at sites considered likely to be
contaminated and sites that represent various land uses within each study unit. Most sites were
sampled once in each medium. In the case of sites sampled more than once, a single sample was
chosen to represent the site in the Pesticide National Synthesis analysis (Nowell, 2003). In the
case of multiple bed sediment samples, the earliest one with complete data for key analytes was
used to represent the site. In the case of multiple tissue samples, the earliest sample from the
first year of sampling that came from the most commonly sampled type offish in the study unit
was selected.
As part of the National Pesticide Synthesis, USGS also analyzed the occurrence of select
semivolatile organic compounds (SVOCs) in bed sediment at sites considered likely to be
contaminated and sites that represent various land uses within each study unit (Nowell and
Capel, 2003). Most sites were sampled only once. When multiple samples were taken, the
earliest one was used to represent the site in the analysis.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 4-2
-------
Over the course of Cycle 1 (1991-2001), NAWQA analytical methods may have been
improved or changed. Hence, reporting levels (RLs) varied over time for some compounds. In
the summary tables, the highest RL for each analyte is presented for general perspective. In the
ground water, bed sediment, and tissue data analyses, the method of calculating concentration
percentiles sometimes varied depending on how much of the data was censored at particular
levels by the laboratory (i.e., because of the relatively large number of non-detections in these
media).
4.2.2 Results
Under the NAWQA program, USGS monitored EPIC between 1992 and 2001 in
representative watersheds and aquifers across the country. Reporting limits varied but did not
exceed 0.002 |ig/L. Results for surface water and ground water are presented in Tables 4-1 and
4-2. EPTC was not monitored in bed sediment or biota.
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of EPTC in
Ambient Surface Water, 1992-2001
Land Use Type
Agricultural
Mixed
Undeveloped
Urban
No. of Samples
(and No. of
Sites)
1,884 (78)
1,000 (47)
60(4)
892 (33)
Detection
Frequency
14.11%
11.88%
1.64%
4.81%
50th Percentile
(Median)
Concentration
-------
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of EPTC in
Ambient Ground Water, 1992-2001
Land Use Type
Agricultural
Mixed (Major
Aquifer)
Undeveloped
Urban
No. of Wells
1,443
2,717
67
834
Detection
Frequency
0.49%
0.33%
0.0%
0.72%
50th Percentile
(Median)
Concentration
-------
monitoring was conducted primarily between 2001 and 2003, some results were not collected
and reported until as late as 2006.
The objective of the UCMR1 sampling approach for small systems was to collect
contaminant occurrence data from a statistically selected, nationally representative sample of
small systems. The small system sample was stratified and population-weighted, and included
some other sampling adjustments such as ensuring the selection of at least two systems from
each State. With contaminant monitoring data from all large PWSs and a statistical, nationally
representative sample of small PWSs, UCMR1 List 1 Assessment Monitoring provides a
contaminant occurrence data set suitable for national drinking water estimates.
4.3.2 CCL Health Reference Level
To evaluate the systems and populations exposed to EPTC through PWSs, the monitoring
data were analyzed against the Minimum Reporting Level (MRL) and a benchmark value for
health that is termed the Health Reference Level (HRL). Two different approaches were used to
derive the HRL, one for chemicals that cause cancer and exhibit a linear response to dose and the
other applies to noncarcinogens and carcinogens evaluated using a non-linear approach.
The RfD for EPTC is 0.025 mg/kg/day based on decreased weight and cardiomyopathy
in treated rats given the chemical in feed (Mackenzie, 1986). Additional detail concerning the
RfD can be found in section 6.2. The Agency established the HRL for EPTC using the RfD and
a 20 percent relative source contribution as follows:
HRL = [(0.025 mg/kg/day x 70 kg)/2 L/day] x 20% = 0.175 mg/L (or 175 |ig/L)
4.3.3 Results
As a List 1 contaminant, EPTC was scheduled to be monitored by all large CWSs and
NTNCWSs and a statistically representative sample of small CWSs and NTNCWSs. The data
presented in this report reflect UCMR1 analytical samples submitted and quality-checked under
the regulation as of March 2006 EPTC data were collected and submitted by 797 (99.6 percent)
of the 800 small systems selected for the small system sample and 3,076 (99.2 percent) of the
3,100 large systems defined as eligible for the UCMR1 large system census. EPTC data have
been analyzed at the level of simple detections (at or above the minimum reporting level,
>MRL, or > 1 |ig/L), exceedances of the health reference level (>HRL, or >175 |ig/L), and
exceedances of one-half the value of the HRL (>/^HRL, or >87.5 |ig/L).
Results of the analysis are presented in Table 4-3 and 4-4. No detections of EPTC were
found in any samples, and thus there were also no exceedances of the HRL or one-half the HRL.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 4-5
-------
Table 4-3 Summary UCMR1 Occurrence Statistics for EPTC in Small Systems (Based
on Statistically Representative National Sample of Small Systems)
Frequency Factors
Total Number of Samples
Percent of Samples with Detections
99 Percentile Concentration (all samples)
Health Reference Level (HRL)
Minimum Reporting Level (MRL)
Maximum Concentration of Detections
99th Percentile Concentration of Detections
Median Concentration of Detections
Total Number of PWSs
Number of GW PWSs
Number of SW PWSs
Total Population
Population of GW PWSs
Population of SW PWSs
Occurrence by System
PWSs (GW & SW) with Detections (> MRL)
PWSs (GW & SW) > 1/2 HRL
PWSs (GW & SW) > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Population Served by PWSs > 1/2 HRL
Population Served by PWSs > HRL
UCMR Data -
Small Systems
3,251
0.00%
ViHRL, or PWSs > HRL = PWSs with at
least one sampling result greater than or equal to the MRL, exceeding the ViHRL benchmark, or exceeding the HRL benchmark, respectively;
Population Served by PWSs with detections, by PWSs >'/2HRL, or by PWSs >HRL = population served by PWSs with at least one sampling
result greater than or equal to the MRL, exceeding the '/zHRL benchmark, or exceeding the HRL benchmark, respectively.
Notes:
-Small systems are those that serve 10,000 persons or fewer.
-Only results at or above the MRL were reported as detections. Concentrations below the MRL are considered non-detects.
-Due to differences between the ratio of GW and SW systems with monitoring results and the national ratio, extrapolated GW and SW figures
might not add up to extrapolated totals.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
4-6
-------
Table 4-4 Summary UCMR1 Occurrence Statistics for EPTC in Large Systems (Based
on the Census of Large Systems)
Frequency Factors
Total Number of Samples
Percent of Samples with Detections
99th Percentile Concentration (all samples)
Health Reference Level (HRL)
Minimum Reporting Level (MRL)
Maximum Concentration of Detections
99th Percentile Concentration of Detections
Median Concentration of Detections
Total Number of PWSs
Number of GW PWSs
Number of SW PWSs
Total Population
Population of GW PWSs
Population of SW PWSs
Occurrence by System
PWSs (GW & SW) with Detections (> MRL)
PWSs (GW & SW) > 1/2 HRL
PWSs (GW & SW) > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Population Served by PWSs > 1/2 HRL
Population Served by PWSs > HRL
UCMR Data -
Large Systems
30,547
0.00%
HHRL, or PWSs > HRL = PWSs with at
least one sampling result greater than or equal to the MRL, exceeding the HHRL benchmark, or exceeding the HRL benchmark, respectively;
Population Served by PWSs with detections, by PWSs >1/2HRL, or by PWSs >HRL = population served by PWSs with at least one sampling
result greater than or equal to the MRL, exceeding the ViHRL benchmark, or exceeding the HRL benchmark, respectively.
Notes:
-Large systems are those that serve more than 10,000 persons.
-Only results at or above the MRL were reported as detections. Concentrations below the MRL are considered non-detects.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
4-7
-------
4.4 Summary
Under the NAWQA program, USGS monitored EPIC between 1992 and 2001 in
representative watersheds and aquifers across the country. The 95th percentile concentrations in
surface water were less than the reporting limit in undeveloped and urban settings, 0.009 |ig/L in
mixed land use settings, and 0.018 |ig/L in agricultural settings. The highest concentration,
estimated at 29.6 |ig/L, was found in a mixed land use setting. The 95th percentile concentrations
in ground water were less than the reporting limit in all settings. EPTC was detected more
frequently in ambient surface water than ambient ground water in all land use settings (1.64% vs.
0% for undeveloped land samples; 4.81% vs. 0.72% for urban samples; 11.88% vs. 0.33% for
mixed land use area samples; and 14.11% vs. 0.49% for agriculture samples).
For UCMR1, EPTC was scheduled to be monitored by all large CWSs and NTNCWSs
and a statistically representative sample of small CWSs and NTNCWSs. The data available in
March of 2006 were analyzed at the level of simple detections (at or above the minimum
reporting level, >MRL, or > 1 |ig/L), exceedances of the health reference level (>HRL, or >175
|ig/L), and exceedances of one-half the value of the HRL (>/^HRL, or >87.5 |ig/L). No
detections of EPTC were found in any samples and, thus, there were also no exceedances of the
HRL or one-half the HRL.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 4-8
-------
5.0 EXPOSURE FROM MEDIA OTHER THAN WATER
5.1 Exposure from Food
5.1.1 Concentration in Non-Fish Food Items
Based on the EPA's Reregi strati on Eligibility Decision (U.S. EPA, 1999), a single
reported EPTC residue of toxicological concern was found in goats (EPTC-cysteine conjugate)
and hens (unmetabolized EPTC) fed "highly exaggerated doses" of EPTC (doses were not
provided). In both cases, the residue was found in low concentrations only (the values were not
presented). EPA concluded that residues of EPTC in animal commodities represent a Category 3
situation under 40 CFR §180.6(a), in which it is impossible to clearly establish whether finite
residues will be incurred under reasonable worst-case exposure scenarios, and there is no
reasonable expectation that finite residues will be present in animal commodities. Therefore,
tolerances for residues of EPTC in animal commodities need not be established (U.S. EPA,
1999). No other studies of EPTC residues in animals were located.
Residues of EPTC and its three hydroxylated metabolites were nondetectable (<0.05
ppm) in the majority of samples of raw and processed agricultural commodities obtained from
submitted field trials (U.S. EPA, 1999).
5.1.2 Concentrations in Fish and Shellfish
Information concerning the concentrations of EPTC found in fish and shellfish was not
found in the literature reviewed.
5.1.3 Intake of EPTC from Food
Based on the information presented, EPTC was not readily detected in food items.
Consequently, the typical average daily intake of EPTC from food for the general population is
anticipated to be close to zero.
5.2 Exposure from Air
5.2.1 Concentration of EPTC in Air
The maximum concentration of EPTC detected over the Mississippi River, encompassing
an area from New Orleans, LA to St. Paul, MN during June 1994, was 1.5 ng/m3 (Majewski et
al., 1998). No other data are currently available.
5.2.2 Intake of EPTC from Air
Estimates of nonoccupational exposures to EPTC for adults can be derived from the
ambient air concentration encompassing an area from New Orleans, LA to St. Paul, MN during
June 1994 (Majewski et al., 1998) using the assumption that adult humans breath 15.2 m3 air per
day (U.S. EPA, 1996b).
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 5-1
-------
1.5 ng/m3 x 15.2 m3/day = 22.8 ng/day rounded to 23 ng/day
For children the average rate for air exchange is 8.7 m3 /day leading to an exposure of
1.5 ng/m3 x 8.7 m3/day = 13.05 ng/day rounded to 13 ng/day
5.3 Exposure from Soil
5.3.1 Concentration of EPTC in Soil
The mean concentration of EPTC at agrochemical facilities in Illinois was determined to
be 110 |-ig/kg (Krapac, 1995). No other data were available.
5.3.2 Intake of EPTC from Soil
Human exposure to contaminants in soils is usually from dust that infiltrate homes,
automobiles etc. in the adult, and from dusts and incidental soil ingestion in children. Estimates
of intake for soil often assume an ingestion rate of 100 mg/day for children and 50 mg/day for
adults (U.S. EPA, 1996b). Using the data from Krapac et al. (1995) of 0.110 mg EPTC/kg soil
and the assumption that infants ingest 0.000001 kg/soil per day (100 mg), exposure of infants to
EPTC from soils would be about 0.11 ng/day and that for adults would be 0.55 ng/day.
0.110 mg/kg soil x 0.000001 kg soil = 0.00000011 mg/day (0.11 ng/day)
0.110 mg/kg soil x 0.0000005 kg soil = 0.00000055 mg/day (0.55 ng/day)
5.4 Other Residential Exposures
Residential handler exposure to EPTC via dermal and inhalation routes can occur during
application activities. The exposure duration of these activities was classified as short-term (1-7
days), because EPTC is usually applied only once per year or during well-spaced intervals. This
prevents excessive concentration buildup.
5.5 Occupational Exposures
5.5.1 Description of Industries and Workplaces
The potential for exposure is greatest at agrochemical production facilities and during
direct (manual) application to crops and non-food flora. Protective measures are necessary to
reduce exposure risks (e.g., personal protective equipment and engineering controls).
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 5-2
-------
5.5.2 Types of Exposure
Occupational and residential exposure to EPIC residues via dermal and inhalation routes
can occur during handling activities such as mixing, loading, and applying. The exposure
duration of application activities was classified as short-term (1-7 days), because EPTC is
usually applied only once per year or applications are well-spaced in time, preventing excessive
concentration buildup.
The potential for post-application occupational exposure is minimal. There is little
chance for post-application dermal exposure because EPTC is directly applied to soil, or injected
into soil well before plants are mature and dissipates rapidly.
5.6 Summary
Based on the data, the general population should not be exposed to EPTC from food
items. Nonoccupational inhalation exposure to EPTC for adults is approximately 23 ng/day. For
children, exposure from ambient air is approximately 13 ng/day. Estimates of EPTC intake from
soils are 0.11 ng/day for infants and 0.55 ng/day for adults. Other residential exposures to EPTC
can occur via dermal and inhalation routes during application activities. The exposure duration
of these activities was classified as short-term (1-7 days) because EPTC is usually applied only
once per year or during well-spaced intervals.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 5-3
-------
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 5-4
-------
6.0 HAZARD AND DOSE-RESPONSE ASSESSMENT
6.1 Characterization of Hazard
6.1.1 Synthesis and Evaluation of Major Noncancer Effects
In a recent human study (Hoppin et al., 2002), EPIC exposure was shown to be
associated with a slight but significant increase in the in the odds ratio for wheezing in farmers
(odds ratio = 1.32; 95% confidence interval = 1.05-1.65; p=0.01). In acute animal toxicity
studies, EPIC is most toxic when exposure is via inhalation; acute responses following oral and
dermal exposures are less severe. In a primary eye irritation study in rabbits, technical EPIC
was shown to be slightly irritating (U.S. EPA, 1999).
An increase in the incidence and severity of cardiomyopathy was observed in subchronic
and chronic studies performed in both rats and dogs. In two chronic/oncogenicity feeding
studies and in 90-day feeding and inhalation studies, all rats exhibited myocardial degeneration
during the histopathology examination (Mackenzie, 1986; U.S. EPA, 1999). In dogs, two
chronic oral dosing studies revealed degenerative changes in the cardiac muscle when EPIC was
administered in a capsule, but not when it was administered at comparable doses in the diet.
Electrocardiograms were performed in both dog studies; however, only one high-dose male in
the capsule study exhibited changes which were described as "potentially" treatment-related
(U.S. EPA, 1999).
EPTC is a reversible cholinesterase (ChE) inhibitor. Similar to other thiocarbamates,
EPTC does not produce a consistent ChE inhibition profile. There were no consistent patterns
observed in any of the toxicity studies with regard to species, duration of treatment, or type of
ChE enzyme measured. Typically studies showed inhibition of plasma ChE with dose-related
increases in red blood cells and brain ChE inhibition. Some studies have shown that brain ChE
activity was inhibited without any effect on either plasma or erythrocyte ChE activities. Other
studies illustrated erythrocyte ChE inhibition with no inhibition of either plasma or brain ChE.
This inconsistent ChE inhibition profile is illustrated when comparing the results of a chronic
dog oral dosing study, in which only plasma ChE was inhibited, and a developmental rabbit
study, in which plasma and erythrocyte ChE were inhibited (U.S. EPA, 1999). In another study
with rats at or near the acute median lethal dose, EPTC inhibited only erythrocyte and brain ChE,
but not plasma ChE (U.S. EPA, 1999).
Exposure to EPTC, as well as other thiocarbamates (molinate, cycloate, pebulate,
vernolate, and butylate), also is associated with toxic effects on the central and peripheral
nervous systems. Both rats and dogs have exhibited increases in incidence and severity of
neuronal necrosis/degeneration in both the central and peripheral nervous systems. In a rat
neurotoxicity study, dose-related increases in the incidence of neuronal necrosis were observed
in the brain after acute and subchronic exposure to EPTC. However, in an acute delayed
neurotoxicity study of EPTC in hens, delayed neurotoxicity was not observed (U.S. EPA, 1999).
Treatment-related neuromuscular lesions were observed in both chronic toxicity/oncogenicity
studies in rats and in a chronic oral (capsule) study in dogs. In all of these studies, hindquarter
weakness was observed and, at necropsy evaluation, atrophy and degeneration of the skeletal
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 6-1
-------
muscle was observed. In the dog study, the lesions were described as Wallerian-type
degeneration in the spinal cords and various peripheral nerves (U.S. EPA, 1999).
Smulders et al. (2003) recently investigated effects of several carbamate pesticides on
neuronal nicotinic acetylcholine receptors (nAChRs) heterologously expressed in Xenopus laevis
oocytes. The potencies of carbamate effects on the nAChRs were then compared to the
potencies of rat brain AChE inhibition and the differential sensitivities of specific subtypes of
ganglionic and brain neuronal nAChRs. The results of this study indicate that in oocytes
expressing the rat a,4$4 nAChR, EPTC caused nearly complete inhibition when applied at a
concentration of 100 |J,M. In contrast, concentrations up to 1 mM of EPTC did not cause a
marked reduction in rat brain AChE activity. The nicotinic acetylcholine receptors subtypes
(«42, «3P4, and a3fi2) also were inhibited by EPTC, with similar potencies to those of a4fi4
receptors. Based on these observations, it was concluded that carbamate pesticides affect
different subtypes of neuronal nicotinic receptors independent of acetylcholinesterase inhibition
potential, and that these effects may contribute to long-term changes in the nervous system.
Maternal and parental developmental and reproductive toxicity were observed in rats and
rabbits exposed to EPTC. In a rat prenatal developmental toxicity study, developmental toxicity
indications (decreased fetal body weight and litter size) were observed, but were considered
secondary to marked maternal toxicity (i.e., increased mortality and decreased body weight)
(U.S. EPA, 1999). Similar results were observed in a rabbit developmental toxicity study in
which a developmental toxicity index (decreased fetal body weight) was observed in the
presence of marked maternal toxicity indices (decreased body weight and increased mortality)
(U.S. EPA, 1999).
A two-generation study conducted in rats fed diets containing 0, 50, 200 or 800 ppm
EPTC. Effects in the offspring were observed only at or above treatment levels that resulted in
parental toxicity. There was a slight decrease in pup body weight in the 800 ppm dose group.
Toxicity was observed in the Fl generation dams as reflected in a dose-related increase in
cardiomyopathy and reduced body weights. Degenerative cardiomyopathy is an abnormality in
the function of the heart muscle, which reduces physical abilities of the affected animal its
including the ability to compete for food and reproductive dominance (U.S. EPA, 1999; Cal
EPA, 1995).
Although the data do not provide evidence of reproductive or developmental toxicity
except at maternally toxic doses, the OPP did register a concern for developmental neurotoxicity
because of the neurodegenerative effects observed in studies in adult animals and for that reason
suggested that a food Quality Protection Act factor of 10 be applied when assessing the
pesticidal uses of this product (U.S. EPA, 1999).
6.1.2 Synthesis and Evaluation of Carcinogenic Effects
In a study conducted by Alavanja et al. (2003), there was no exposure-response
association between EPTC exposure and prostate cancer. In another study, Zheng et al. (2001)
examined the risk of non-Hodgkin lymphoma (NHL) from carbamate insecticide exposure using
a pooled analysis of three-population based case-control studies. There was an increased risk of
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 6-2
-------
NHL (30 to 50%) among farmers who had used carbamate pesticides as a group when compared
to non-farmers. For those who used EPIC plus protectant (protectant not specified) for less than
7 years the association was not as strong (odds ratio = 2.2; 95% confidence interval = 1.1-4.4);
the odds ratio among the farmers that used EPTC for $7 years was not significant but this may
be due to the small number of cases.
There are a number of chronic animal studies of EPTC which included evaluation of the
cancer endpoint. A 78-week study in mice (Tisdel et al., 1986) and a 2-year study in rats
(Dickie, 1987), both demonstrated that there was no significant increase in tumors when the
exposed animals were compared to the controls. The Tisdale et al., (1986) study used dietary
concentrations ranging from 0 to 1,800 ppm; the Dickie study used doses of 0 to 72 mg/kg/day
technical grade EPTC in the diet.
Based on the information provided, it does not appear that exposure to EPTC is
carcinogenic. Limited studies in humans do not implicate carbamate in the etiology for prostate
cancer and show only a weak association with NHL. Bioassays in rats and mice indicate that
exposure to EPTC does not result in an increased incidence of neoplastic lesions.
6.1.3 Mode of Action and Implications in Cancer Assessment
This section is not applicable because EPTC shows no evidence of carcinogenicity (as
described in Section 6.1.2, Synthesis and Evaluation of Carcinogenic Effects).
6.1.4 Weight of Evidence Evaluation for Carcinogenicity
Applying the criteria described in EPA's draft final guidelines for assessment of
carcinogenic risk (U.S. EPA, 2005), EPTC may be classified as not likely to be carcinogenic to
humans. This group is for agents with animal evidence that demonstrate lack of carcinogenic
effects in well-designed and well-conducted studies in at least two appropriate animal species (in
the absence of other animal or human data suggesting a potential for cancer effects); extensive
experimental evidence showing that the only carcinogenic effects observed in animals are not
relevant to humans; convincing evidence that carcinogenic effects are not likely to occur by a
particular exposure route; or convincing evidence that carcinogenic effects are not likely to occur
below a defined dose range.
6.1.5 Potentially Sensitive Populations
Results from both developmental and reproductive studies indicate that minimal adverse
effects on body weight occur in pups in animal studies at maternally toxic doses after EPTC
exposure. However, additional studies focusing on the potential for neurotoxic effects (neuronal
necrosis and degeneration) after pre- and post-natal exposures are needed. Accordingly, there is
some hypothetical concern that children may be a sensitive population for EPTC exposure.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 6-3
-------
6.2 Reference Dose
The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a
daily oral exposure to the human population (including sensitive subgroups) that is likely to be
without an appreciable risk of deleterious effects during a lifetime. The RfD is derived from the
no observed adverse effect level (NOAEL) in the critical or most sensitive study, which is then
divided by a variable uncertainty factor. The RfD for EPTC is 0.025 mg/kg/day. The
subsections below describe how this value was determined.
6.2.1 Choice of Principle Study and Critical Effect
The principal study for determining the RfD is a 2-generation rat reproductive study, in
which Crl:CD(SD)Br rats (30/sex/group) were fed diets providing 0, 50, 200, and 800 ppm
EPTC (equivalent to 0, 2.5, 10, and 40 mg/kg/day, respectively) (Mackenzie, 1986). At doses of
200 ppm and above, parental toxicity consisted of reduced body weights and weight gains, and a
dose-related increased incidence of degenerative cardiomyopathy. Reproductive/developmental
toxicity consisted of reduced pup weights at 800 ppm in both generations. The 50 ppm
concentration was identified as the NOAEL in this study.
6.2.2 Dose-response Characterization (dose conversion if needed)
Doses in the Mackenzie (1986) study were converted from ppm to mg/kg/day using the
assumption that 1 ppm was equivalent to 0.05 mg/kg/day (U.S. EPA, 1987). Accordingly, the
NOAEL of 50 ppm is equivalent to a dose of 2.5 mg/kg/day (U.S.EPA, 1987).
6.2.3 Method of Analysis
U.S. EPA (1987) derived the RFD for EPTC using the NOAEL/LOAEL approach. The
RfD was calculated as follows:
RfD = 2.5 mg/kg/dav = 0.025 mg/kg/day
100
Where:
2.5 mg/kg/day = The NOAEL for cardiomyopathy in the dams from a
two-generation study.
100 = An uncertainty factor that includes a 10 to adjust for interspecies
variability and a 10 for interspecies variability.
6.2.4 Application of Uncertainty Factor(s) and Modifying Factor(s)
An uncertainty factor of 100 was used for the RfD derivation (10 for interspecies
extrapolation and 10 for intraspecies variability). The Agency did not apply uncertainty factors
for the database or for a duration adjustment. However, the need for a study of developmental
neurotoxicity was noted and the Office of Pesticide Programs recommended use of a Food
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 6-4
-------
Quality Protection Act factor of 10 when setting tolerances for EPTC until this data need is
filled.
6.3 Carcinogen Assessment
This section is not applicable because EPTC shows no evidence of carcinogenicity (as
described in Section 6.1.2, Synthesis and Evaluation of Carcinogenic Effects).
6.4 Sensitive Population Considerations
The OPP identified children as a potentially sensitive population because of the neuronal
degeneration noted in the central and peripheral nervous system in mature rats and dogs and
because these same effects have been observed in studies of other thiocarbamates. Although the
RfD is protective of these effects in mature animals, a study of developmental neurotoxicity was
identified as a data need by the Office of Pesticide Programs.
6.5 Post Re-registration Health Effects Publications
Not applicable
6.6 CCL Health Reference Level
The CCL health reference level is 0.175 mg/L. EPA derived the HRL using an RfD
approach as follows: HRL = (RfD x?0 kg)/2 L/day x RSC, where:
RfD = An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily
oral exposure (mg/kg/day) to the human population (including sensitive subgroups) that
is likely to be without an appreciable risk of deleterious effects during a lifetime. It can
be derived from an NOAEL, LOAEL, or BMD, with uncertainty factors generally
applied to reflect limitations of the data used;
70 kg = The assumed body weight of an adult;
2 L = The assumed daily water consumption of an adult;
RSC = The relative source contribution, or the level of exposure believed to result
from drinking water when compared to other sources (e.g., air), and is assumed to
be 20% unless noted otherwise.
Therefore, the HRL = 0.025 mg/kg/dav x 70kg x Q.20 = 0.0.175 mg/L
2L/day
A discussion of the HRL as a benchmark for evaluating occurrence using monitoring data from
public water systems is found in Section 4.3.2.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 6-5
-------
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
-------
7.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK
FROM DRINKING WATER
7.1 Regulatory Determination for Chemicals on the CCL
The Safe Drinking Water Act (SDWA), as amended in 1996, required the Environmental
Protection Agency (EPA) to establish a list of contaminants to aid the Agency in regulatory
priority setting for the drinking water program. EPA published a draft of the first Contaminant
Candidate List (CCL) on October 6, 1997 (62 Federal Register [FR] 52193, U.S. EPA, 1997).
After review of and response to comments, the final CCL was published on March 2, 1998 (63
FR 10273, U.S. EPA, 1998c).
On July 18, 2003 EPA announced final Regulatory Determinations for one microbe and 8
chemicals (68 FR 42897, U.S. EPA, 2003) after proposing those determinations on June 3, 2002
(67 FR 38222, U.S. EPA, 2002b). The remaining 40 chemicals and ten microbial agents from
the first CCL became CCL 2 and were published in the Federal Register on April 2, 2004 (69 FR
17406, U.S. EPA 2004b).
EPA proposed Regulatory Determinations for 11 chemicals from CCL2 on May 1, 2007
(72FR 24016;U.S. EPA, 2007). Determinations for all 11 chemicals were negative based on a
lack of national occurrence at levels of health concern. The Agency is given the freedom to
determine that there is no need for a regulation if a chemical on the CCL fails to meet one of
three criteria established by the SDWA and described in section 7.1.1. After review of public
comments and submitted data, the negative determinations for the 11 contaminants have been
retained. Each contaminant will be considered in the development of future CCLs if there are
changes in health effects and/or occurrence.
7.1.1 Criteria for Regulatory Determination
These are the three criteria used to determine whether or not to regulate a chemical on the
CCL:
• The contaminant may have an adverse effect on the health of persons.
The contaminant is known to occur or there is a substantial likelihood that the
contaminant will occur in public water systems with a frequency and at levels of
public health concern.
• In the sole judgment of the Administrator, regulation of such contaminant presents a
meaningful opportunity for health risk reduction for persons served by public water
systems.
The findings for all criteria are used in making a determination to regulate a contaminant.
As required by the SDWA, a decision to regulate commits the EPA to publication of a Maximum
Contaminant Level Goal (MCLG) and promulgation of a National Primary Drinking Water
Regulation (NPDWR) for that contaminant. The Agency may determine that there is no need for
a regulation when a contaminant fails to meet one of the criteria. A decision not to regulate is
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-1
-------
considered a final Agency action and is subject to judicial review. The Agency can choose to
publish a Health Advisory (a nonregulatory action) or other guidance for any contaminant on the
CCL independent of the regulatory determination.
7.1.2 National Drinking Water Advisory Council Recommendations
In March 2000, the EPA convened a Working Group under the National Drinking Water
Advisory Council (NDWAC) to help develop an approach for making regulatory determinations.
The Working Group developed a protocol for analyzing and presenting the available scientific
data and recommended methods to identify and document the rationale supporting a regulatory
determination decision. The NDWAC Working Group report was presented to and accepted by
the entire NDWAC in July 2000.
Because of the intrinsic difference between microbial and chemical contaminants, the
Working Group developed separate but similar protocols for microorganisms and chemicals.
The approach for chemicals was based on an assessment of the impact of acute, chronic, and
lifetime exposures, as well as a risk assessment that includes evaluation of occurrence, fate, and
dose-response. The NDWAC protocol for chemicals is a semi-quantitative tool for addressing
each of the three CCL criteria. The NDWAC requested that the Agency use good judgment in
balancing the many factors that need to be considered in making a regulatory determination.
The EPA modified the semi-quantitative NDWAC suggestions for evaluating chemicals
against the regulatory determination criteria and applied them in decision-making. The
quantitative and qualitative factors for s-ethyl dipropylthiocarbamate (EPTC) that were
considered for each of the three criteria are presented in the sections that follow.
7.2 Health Effects
The first criterion asks if the contaminant may have an adverse effect on the health of
persons. Because chemicals have adverse effects at some level of exposure, the challenge is to
define the dose at which adverse health effects are likely to occur, and estimate a dose at which
adverse health effects are either not likely to occur (threshold toxicant), or have a low probability
for occurrence (non-threshold toxicant). The key elements that must be considered in evaluating
the first criterion are the mode of action, the critical effect(s), the dose-response for critical
effect(s), the reference dose (RfD) for threshold effects, and the slope factor for nonthreshold
effects.
A full description of the health effects information and dose-response assessment
associated with exposure to ETPC is presented in Chapter 6 of this document and summarized
below in Sections 7.2.1, 7.2.2 and 7.2.3.
7.2.1 Health Criterion Conclusion
Results of studies have shown that EPTC is a reversible cholinesterase (ChE) inhibitor.
Similar to other thiocarbamates, EPTC does not produce a consistent ChE inhibition profile;
consequently, there is no consistent pattern observed in any of the toxicity studies with regard to
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-2
-------
species, duration of treatment, or the type of ChE enzyme measured (U.S. EPA, 1999). EPTC
exposure also is associated with toxic effects on the central and peripheral nervous system. In
acute animal toxicity studies, EPTC was shown to be moderately toxic via oral and dermal
routes, and highly toxic via inhalation. In subchronic and chronic studies performed in both rats
and dogs, there was an increase in the incidence and severity of cardiomyopathy (Mackenzie,
1986; U.S. EPA, 1999).
The oral RfD for EPTC is 0.025 mg/kg/day, and the health reference level (HRL) for
EPTC is calculated to be 0.175 mg/L. EPTC is classifiable as not likely to be carcinogenic to
humans based on lack of evidence of carcinogenic effects in long term studies in rats and mice
(U.S. EPA, 1987; U.S. EPA, 2005). Based on these considerations, the evaluation of the first
criterion for EPTC is positive; EPTC may have an adverse effect on human health.
7.2.2 Hazard Characterization and Mode of Action Implications
In an epidemiological study of farmers, EPTC was associated with a slight increase in the
relative risk for wheezing. In animals, acute toxicity studies have shown that EPTC is
moderately toxic via oral and dermal routes, and is highly toxic when exposure is via inhalation.
EPTC also is a reversible cholinesterase (ChE) inhibitor. Similar to other thiocarbamates, EPTC
does not produce a consistent ChE inhibition profile. There were no consistent patterns observed
in any of the toxicity studies with regard to species, duration of treatment, or type of ChE
enzyme measured. Typically studies showed inhibition of erythrocyte and brain ChE; however,
some studies have shown that brain ChE activity was inhibited without any effect on either
plasma or erythrocyte ChE activities while others have identified erythrocyte ChE inhibition
with no inhibition of either plasma or brain ChE (U.S. EPA, 1999). In a primary eye irritation
study in rabbits, technical-grade EPTC was shown to be slightly irritating (U.S. EPA, 1999).
An increase in the incidence and severity of cardiomyopathy was observed in subchronic
and chronic studies performed in both rats and dogs (Mackenzie, 1986; U.S. EPA, 1999).
Additionally, the central and peripheral nervous systems also are affected by EPTC exposure
with rats and dogs exhibiting an increase in the incidence and severity of degenerative effects
(neuronal and/or necrotic degeneration) (U.S. EPA, 1999).
In addition to its neurotoxic effects, EPTC has the ability to induce maternal and
reproductive toxicity and secondary developmental toxicity in exposed rats and rabbits. In a rat
developmental toxicity study, as well as a rabbit developmental toxicity study, toxicity
indications (decreased fetal body weight and litter size for rats; decreased fetal body weight for
rabbits) were observed, but were considered secondary to observed marked maternal toxicity
(increased mortality and decreased body weight for rats; decreased body weight and increased
mortality for rabbits) (U.S. EPA, 1999). In a two-generation reproduction study in rats, effects
in the offspring were observed only at or above treatment levels that resulted in parental toxicity
(Mackenzie, 1986; U.S. EPA, 1999).
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-3
-------
7.2.3 Dose-Response Characterization and Implications in Risk Assessment
The RfD for EPIC is 0.025 mg/kg/day (U.S. EPA, 1987; U.S. EPA, 1999). This value
was calculated using an NOAEL of 2.5 mg/kg/day from a study by Mackenzie (1986) and
applying an uncertainty factor of 100 for inter- and intraspecies differences. The critical effect
associated with the RfD is cardiomyopathy (disease of the heart muscle). EPA determined that
the HRL is 0.175 mg/L or 175 |ig/L for EPTC, using the RfD of 0.025 mg/kg/day and a 20
percent relative source contribution.
The Agency used long-term studies in mice and rats and short-term studies of
mutagenicity to evaluate the potential for carcinogenicity. Based on these data and using EPA's
2005 Guidelines for Carcinogen Risk Assessment, EPTC is not likely to be carcinogenic to
humans (U.S. EPA, 2005).
EPA also evaluated whether health information is available regarding the potential
effects on children and other sensitive populations. Data do not suggest increased pre- or
post-natal sensitivity of children and infants to EPTC exposure because developmental adverse
effects observed were considered secondary to maternal effects (U.S. EPA, 1999). Although
results from both developmental and reproductive studies indicate that minimal adverse effects
occur in fetuses or offspring in animal studies after EPTC exposure, additional studies focusing
on the neurotoxic effects (neuronal necrosis and degeneration) are needed. The behavior
patterns of children that lead to heightened opportunities for exposure in the indoor environment
and the need for a developmental neurotoxicity study lead OPP to recommend the application of
a ten-fold FQPA factor for EPTC.
7.3 Occurrence in Public Water Systems
The second criterion asks if the contaminant is known to occur or if there is a substantial
likelihood that the contaminant will occur in public water systems with a frequency and at levels
of public health concern. In order to address this question the following information was
considered:
• Monitoring data from public water systems
• Ambient water concentrations and releases to the environment
• Environmental fate
Data on the occurrence of EPTC in public drinking water systems were the most
important determinants in evaluating the second criterion. EPA looked at the total number of
systems that reported detections of EPTC, as well those that reported concentrations of EPTC
above an estimated drinking-water HRL. For noncarcinogens, the estimated FIRL level was
calculated from the RfD assuming that 20% of the total exposure would come from drinking.
For carcinogens, the HRL was the 10"6 risk level (i.e, the probability of 1 excess tumor in a
population of a million people). The FtRLs are benchmark values that were used in evaluating
the occurrence data while the risk assessments for the contaminants were being developed.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-4
-------
The available monitoring data, including indications of whether or not the contaminant is
a national or a regional problem, are included in Chapter 4 of this document and summarized
below. Additional information on production, use, and fate are found in Chapters 2 and 3.
7.3.1 Occurrence Criterion Conclusion
There were no detections of EPTC found in any of the large (i.e., serving more than
10,000 people) community water systems (CWSs) and large non-transient non-community water
systems (NTNCWSs). There were no detections of EPTC found in the statistically
representative national sample of 800 small (i.e., serving 10,000 people or fewer) CWSs and
NTNCWSs. Additionally, the available data for EPTC production and environmental releases all
show a downward trend (NCFAP, 2004).
The physiochemical properties of EPTC suggest that EPTC does not persist in the
environment due to rapid dissipation rates and high volatility. However, estimated
bioconcentration rates in aquatic organisms is moderate, assuming the chemical persists long
enough to be taken up by an organism (U.S. EPA, 2005).
Based on the occurrence data, it is unlikely that EPTC will occur in public water systems
at frequencies or concentration levels that are of public health concern. Thus, the evaluation for
the second criterion is negative.
7.3.2 Monitoring Data
Under the National Water-Quality Assessment (NAWQA) program, the US Geological
Survey (USGS) monitored EPTC between 1992 and 2001 in representative watersheds and
aquifers across the country. Reporting limits varied but did not exceed 0.002 |-ig/L. In surface
water, EPTC was detected at frequencies ranging from 1.64% of samples in undeveloped land
settings to 4.81% in urban land-use settings, 11.88% in mixed land use settings, and 14.11% in
agricultural land use settings. The 95th percentile concentrations in all land-use settings were
below the reporting limit in undeveloped and urban settings, 0.009 |-ig/L in mixed land-use
settings, and 0.018 |-ig/L in agricultural settings. The highest maximum concentration, estimated
at 29.6 |ig/L, occurred in an agricultural land-use setting (Martin et al., 2003).
In ground water, EPTC detection frequencies ranged from 0.0% of samples in
undeveloped settings to 0.33% in mixed land-use (major aquifer) settings, 0.49% in agricultural
settings, and 0.72% in urban settings. The 95th percentile concentrations were less than the
reporting limit in all settings. The highest concentration, 0.45 |ig/L, occurred in an agricultural
setting (Kolpin and Martin, 2003).
Additionally, the first Unregulated Contaminant Monitoring Regulation (UCMR1)
collected information on the national occurrence of select emerging contaminants in drinking
water. Although UCMR 1 monitoring was conducted primarily between 2001 and 2003, some
results were not collected and reported until as late as 2006. All large (i.e., serving more than
10,000 people) CWSs and large NTNCWSs, plus a statistically representative national sample of
800 small (i.e., serving 10,000 people or fewer) CWSs and NTNCWSs were required to
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 7-5
-------
participate. The small system sample is population-weighted and was expressly designed to
provide UCMR1 contaminant monitoring results that are statistically representative of national
contaminant occurrence.
The monitoring data available through March 2006 were analyzed and indicate that there
were no detections of EPTC in any of the 33,798 samples collected from 3,873 systems.
Consequently, there also were no exceedances of the HRL or one-half of the HRL.
7.3.3 Use and Fate Data
EPTC is a pre-emergence or early post-emergence herbicide used to control the growth
of germinating annual weeds such as broadleaves, grasses, and sedges. The major usage, in terms
of total pounds of active ingredient, is in fields used to grow crops like corn, potatoes, dry beans
and peas, alfalfa, and snap beans (U.S. EPA, 1999). EPTC also is used at residential and public
sites such as parks, gardens, and golf courses (HSDB, 2004).
The physiochemical properties of EPTC suggest that it does not persist in the
environment due to rapid dissipation rates. EPTC is highly volatile. Terrestrial field studies
indicated a range of dissipation half-lives between 2 and 18.8 days while laboratory tests to
measure dissipation rates indicated half-lives in the range of 36-75 days (U.S. EPA, 1999). The
risk of exposure to EPTC through food or groundwater is minimal due to its rapid rate of
dissipation and normally early (pre-emergent) plant application. However, estimated
bioconcentration rates in aquatic organisms are moderate, assuming the chemical persists long
enough to be taken up by an organism (U.S. EPA, 1999).
The available data for EPTC production and environmental releases all show a downward
trend (NCFAP, 2004). EPTC moved from being the eighth most common pesticide ingredient in
1987 to the nineteenth in 1999. Toxic Release Inventory (TRI) data for EPTC are reported for
the years 1995 to 2002 (U.S. EPA, 2004a). Total reported EPTC releases fluctuated widely in
the range of thousands of pounds per year during this period but generally displayed a declining
trend for most years; releases to surface waters were low.
Monitoring data from public water systems are supportive of a decline in the presence of
EPTC in the environment. Monitoring data to date indicate that there were no detections of
EPTC in any of the 33,798 finished water samples evaluated. Consequently, there also were no
exceedances of the HRL or one-half of the HRL.
7.4 Risk Reduction
The third criterion asks if, in the sole judgment of the Administrator, regulation presents
a meaningful opportunity for health risk reduction for persons served by public water systems.
In evaluating this criterion, EPA looked at the total exposed population, as well as the population
exposed to levels above the estimated HRL. Estimates of the populations exposed and the levels
to which they are exposed were derived from the monitoring results. These estimates are
included in Chapter 4 of this document and summarized in section 7.4.2 below.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-6
-------
In order to evaluate risk from exposure through drinking water, EPA considered the net
environmental exposure in comparison to exposure through drinking water. For example, if
exposure to a contaminant occurs primarily through ambient air, regulation of emissions to air
provides a more meaningful opportunity for EPA to reduce risk than does regulation of the
contaminant in drinking water. In making the regulatory determination, the available
information on exposure through drinking water (Chapter 4) and information on exposure
through other media (Chapter 5) were used to estimate the fraction that drinking water
contributes to the total exposure. The EPA findings are discussed in Section 7.4.3 below.
In making its regulatory determination, EPA also evaluated effects on potentially
sensitive populations, including the fetus, infants and children. Sensitive population
considerations are included in section 7.4.4.
7.4.1 Risk Criterion Conclusion
The presence of EPTC in water is rare. To date, there have been no detections of EPTC
in any of the samples. Consequently, there also have been no exceedances of the HRL or one-
half of the HRL. Thus, the evaluation of the third criterion is negative.
7.4.2 Exposed Population Estimates
EPTC was monitored in all large (i.e., serving more than 10,000 people) community
water systems (CWSs) and large non-transient non-community water systems (NTNCWSs), with
the additon of a statistically representative national sample of 800 small (i.e., serving 10,000
people or fewer) CWSs and NTNCWSs under the UCMR1. There were no detections of EPTC
in any of the samples. Therefore, it appears that the general population is not exposed to EPTC
through water consumption or use.
7.4.3 Relative Source Contribution
Relative source contribution analysis compares the magnitude of exposure expected via
drinking water to the magnitude of exposure from intake of EPTC in other media, such as food,
air, and soil. In situations where EPTC occurs in drinking water, the water is likely to be the
major source of exposure. Intake values found in food, soil, and air are very low (if detectable at
all), and therefore, the RSC value should remain the default value of 20% were a lifetime HA to
be developed for noncancer effects.
7.4.4 Sensitive Populations
Data do not suggest increased pre- or post-natal sensitivity of children and infants to
EPTC exposure because developmental adverse effects observed in test animals were considered
secondary to maternal effects. Although results from both developmental and reproductive
studies indicate that minimal adverse effects occur in fetuses or offspring in animal studies after
EPTC exposure, additional studies focusing on the neurotoxic effects (neuronal necrosis and
degeneration) have been recommended by the Office of Pesticide programs under the Food
Quality Protection Act requirements.
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 7-7
-------
7.5 Regulatory Determination Decision
As stated in Section 7.1.1, a positive finding for all three criteria is required in order to
make a determination to regulate a contaminant. In the case of EPTC, only the finding for the
criterion on health effects is positive. EPTC may have an adverse effect on the health of
persons. No detections of EPTC were found in any UCMR1 drinking water samples. Therefore,
it appears that the general population is not exposed to EPTC through water consumption or use.
On the basis of these observations, the impact of regulating EPTC concentrations in drinking
water on health risk reduction is likely to be small. Regulation of EPTC in public water systems
does not appear to present a meaningful opportunity for health risk reduction.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008
-------
8.0 REFERENCES
Alavanja M.C.R., C. Samanic, M. Dosemeci, et al. 2003. Use of agricultural pesticides and
prostate cancer risk in the agricultural health study cohort. Am. J. Epidemiol. 157:800-814.
Cal EPA (California. Environmental Protection Agency). 1995. EPIC (S-ethyl-
dipropylthiocarbamamte) risk characterization document. Medical Toxicology and Worker
Health and Safety Branches. Department of Pesticide Registration. California Environmental
Protection Agency. Available from: .
Chemfmder.com. 2004. CambridgeSoft Corporation. Available from:
.
Dickie, B.C. 1987. Two-year oral feeding study of the oncogenicity and chronic toxicity of
EPTC in rats: Hazelton Laboratories America, Inc. PPG Industries, Inc. Study No. 6100-106.
DPR Vol. 117-069 #55491 (as cited in Cal EPA, 1995).
Hamilton, P.A., T.L. Miller, and D.N. Myers. 2004. Water quality in the nation's streams and
aquifers: overview of selected findings, 1991-2001. USGS Circular 1265. Available from:
. Link to document from:
.
Hansch, C., A. Leo, and D. Hoekman. 1995. Exploring QSAR - Hydrophobic, electronic, and
steric constants. Washington, DC: American Chemical Society, p. 65 (as cited in HSDB, 2004).
Hoppin J.A., D.M. Umbach, SJ. London, et al. 2002. Chemical predictors of wheeze among
farmer pesticide applicators in the Agricultural Health Study. Am. J. Respir. Crit. Care Med.
165:683-689.
HSDB (Hazardous Substance Data Bank). 2004. EPTAM. Division of Specialized Information
Services, National Library of Medicine. Available from: .
Kolpin, D.W. and J.D. Martin. 2003. Pesticides in Ground water: summary statistics; preliminary
results from Cycle I of the National Water Quality Assessment Program (NAWQA), 1992-2001.
Available from: . Link to
document from: .
Krapac, I.G., W.R. Roy, C.A. Smyth, et al. 1995. Occurrence and distribution of pesticides in
soil at agrichemical facilities in Illinois. J. Soil Contam. 4:209-226 (as cited in HSDB, 2004).
Leahy, P.P. and T.H. Thompson. 1994. The National Water-Quality Assessment Program. U.S.
Geological Survey Open-File Report 94-70. p. 4. Available from:
.
Mackenzie, K. 1986. Two-generation reproduction study with EPTC in rats: Report: Study No.
6100-108 [unpublished study]. Hazleton Laboratories America, Inc.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 8-1
-------
Majewski, M.S., W.T. Foreman, D.A. Goolsby, et al. 1998. Airborne pesticide residues along the
Mississippi River. Environ. Sci. Technol. 32:3689-98 (as cited in HSDB, 2004).
Martin, J.D., C.G. Crawford, and SJ. Larson. 2003. Pesticides in Streams: summary statistics;
preliminary results from Cycle I of the National Water Quality Assessment Program (NAWQA),
1992-2001. Available from:
Link to document from:
Nagy I. et al. 1987. Proceedings British Crop Protection Conference - Weeds 2:525-30 (as cited
in HSDB, 2004).
Nash, R.G. 1983. Determining environmental fate of pesticides with microagroecosystems.
Residue Rev. 85:199-215 (as cited in HSDB, 2004).
NCFAP (National Center for Food and Agricultural Policy). 2004. National Pesticide Use
Database. Available from: .
Nowell, L. 2003. Organochlorine pesticides and PCBs in bed sediment and aquatic biota from
United States rivers and streams: summary statistics; preliminary results of the National Water
Quality Assessment Program (NAWQA), 1992-2001. Available from:
.
Nowell, L. and P. Capel. 2003. Semivolatile organic compounds (SVOC) in bed sediment from
United States rivers and streams: summary statistics; preliminary results of the National Water
Quality Assessment Program (NAWQA), 1992-2001. Available from:
.
NRC (National Research Council). 1983. Risk assessment in the federal government: managing
the process. Washington, DC: National Academy Press.
NRC (National Research Council). 2002. Opportunities to improve the U.S. geological survey
National Water Quality Assessment Program. National Academy Press, p. 238. Available from:
.
Smith, A.E. and A. Fitzpatrick. 1971. A thin-layer chromatographic procedure for the detection
in soils and waters of herbicide residues commonly used in Saskatchewan. J. Chromatogr.
57:303-8 (as cited in HSDB, 2004).
Smulders C.J.G.M., T.J.H. Bueters, R.G.D.M. Van Kleef, et al. 2003. Selective effects of
carbamate pesticides on rat neuronal nicotinic acetylcholine receptors and rat brain
acetylcholinesterase. Toxicol. Appl. Pharmacol. 193:139-146.
Tisdel, M., S. Kehoe, J.L. Carter, et al. 1986. Oncogenicity study in mice with EPTC: Hazelton
Laboratories America, Inc. PPG Industries Inc. Study No 6100-1 04. DPR Vol. 117-049 #45704
(as cited in Cal EPA, 1995).
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 8-2
-------
U.S. EPA (United States Environmental Protection Agency). 1986a. Guidelines for the health
risk assessment of chemical mixtures. Fed. Reg. 51:34014-34025.
U.S. EPA (United States Environmental Protection Agency). 1986b. Guidelines for mutagenicity
risk assessment. Fed. Reg. 51:34006-34012.
U.S. EPA (United States Environmental Protection Agency). 1987. S-Ethyl
dipropylthiocarbamate (EPIC) Integrated Risk Information System. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 1988. Recommendations for and
documentation of biological values for use in risk assessment. EPA 600/6-87/008. Available
from: National Technical Information Service, Springfield, VA; PB88-179874/AS.
U.S. EPA (United States Environmental Protection Agency). 1991. Guidelines for
developmental toxicity risk assessment. Fed. Reg. 56:63798-63826.
U.S. EPA (United States Environmental Protection Agency). 1994a. Interim policy for particle
size and limit concentration issues in inhalation toxicity studies. Fed. Reg. 59:53799.
U.S. EPA (United States Environmental Protection Agency). 1994b. Methods for derivation of
inhalation reference concentrations and application of inhalation dosimetry. EPA/600/8-90/066F.
Available from: National Technical Information Service, Springfield, VA; PB2000-500023, and
.
U.S. EPA (United States Environmental Protection Agency). 1995. Use of the benchmark dose
approach in health risk assessment. U.S. Environmental Protection Agency. EPA/630/R-94/007.
Available from: National Technical Information Service (NTIS) , Springfield, VA; PB95-
213765, and .
U.S. EPA (United States Environmental Protection Agency. 1996a. Guidelines for reproductive
toxicity risk assessment. Fed. Reg. 61:56274-56322.
U.S. EPA (United States Environmental Protection Agency). 1996b. Exposure factors handbook.
U.S. Environmental Protection Agency, Office of Research and Development, Washington, D.C.
EPA/600/8-89/043.1
U.S. EPA (United States Environmental Protection Agency). 1997. Announcement of the draft
Drinking Water Contaminant Candidate List. Fed. Reg.62:52193-52219.
U.S. EPA (United States Environmental Protection Agency). 1998a. Guidelines for neurotoxicity
risk assessment. Fed. Reg. 63:26926-26954.
U.S. EPA (United States Environmental Protection Agency). 1998b. Science policy council
handbook: peer review. Prepared by the Office of Science Policy, Office of Research and
Development, Washington, DC. EPA 100-B-98-001. Available from: National Technical
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 8-3
-------
Information Service, Springfield, VA; PB98-140726, and
.
U.S. EPA (United States Environmental Protection Agency). 1998c. Announcement of the draft
Drinking Water Contaminant Candidate List. Fed. Reg. 63:10273-10287.
U.S. EPA (United States Environmental Protection Agency). 1999. Reregi strati on eligibility
decision. EPIC. EPA 738-R-99-006. Washington, DC: U.S. EPA Office of Prevention,
Pesticides and Toxic Substances.
U.S. EPA (United States Environmental Protection Agency). 2000a. Science policy council
handbook: peer review. 2nd edition. Prepared by the Office of Science Policy, Office of
Research and Development, Washington, DC. EPA 100-B-OO-OOl. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 2000b. Science policy council
handbook: risk characterization. Prepared by the Office of Science Policy, Office of Research
and Development, Washington, DC. EPA 100-B-00-002. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 2000c. Benchmark dose technical
guidance document [external review draft]. EPA/630/R-00/001. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 2000d. Supplemental guidance for
conducting for health risk assessment of chemical mixtures. EPA/630/R-00/002. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 2002a. A review of the reference
dose and reference concentration processes. Risk Assessment Forum, Washington, DC;
EPA/630/P-02/0002F. Available from: .
U.S. EPA (United States Environmental Protection Agency). 2002b. Announcement of
preliminary regulatory determinations for priority contaminants on the drinking water. Fed. Reg.
67:38222-38244.
U.S. EPA (United States Environmental Protection Agency). 2003. Announcement of regulatory
determinations for priority contaminants on the Drinking Water Contaminant Candidate List.
Fed. Reg. 68:42897-42906.
U.S. EPA (United States Environmental Protection Agency). 2004a. TRI Explorer: trends.
Search for ethyl dipropylthiocarbamate. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 2004b. Drinking Water
Contaminant Candidate List 2; Notice. Fed. Reg. 69:17406-17415.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 8-4
-------
U.S. EPA (United States Environmental Protection Agency). 2005. Guidelines for carcinogen
risk assessment. Risk Assessment Forum, Washington, DC; EPA/630/P-03/001B. Available
from: .
U.S. EPA(United States Environmental Protection Agency). 2007. Drinking Water: Regulatory
Determinations Regarding Contaminants on the Second Drinking Water Contaminant Candidate
List - Preliminary Determinations: Proposed Rule Fed. Reg. 72(83):24016-24058.
USGS (United States Geological Survey). 2001. Summary publications from 51 NAWQA study
units sampled in 1991-2001. Available from: .
Zheng T., S.H. Zahm, K.P. Cantor, et al. 2001. Agricultural exposure to carbamate pesticides
and risk of non-Hodgkin lymphoma. J. Occup. Environ. Med. 43:641-649.
S-Ethyl dipropylthiocarbamate (EPTC) —January, 2008 8-5
-------
-------
APPENDIX A: Abbreviations and Acronyms
atm
BCF
BMD
CAS
CCL
ChE
cm
cws
EPA
EPIC
FR
Hg
HRL
HSDB
kg
Koc
Kow
L
LOAEL
m
MCLG
mg
mL
mm
mM
MRL
nAChR
NAWQA
NCFAP
NCOD
NDWAC
NOAEL
NPDWR
NHL
NTNCWS
OPP
PBPK
ppm
PWS
QAPP
RED
RfD
RL
RSC
atmosphere
bioaccumulation factor
benchmark dose
Chemical Abstracts Registry
Contaminant Candidate List
cholinesterase
centimeter
community water system
Environmental Protection Agency
S-Ethyl dipropylthiocarbamate
Federal Register
mercury
health reference level
Hazardous Substances Database
kilogram
organic carbon partitioning coefficient
octanol-water partition coefficient
liter
lowest observed adverse effect level
meter
Maximum Contaminant Level Goal
milligram
milliliter
millimeter
millimolar
minimum reporting level
nicotinic acetylcholine receptor
National Water Quality Assessment
National Center for Food and Agricultural Policy
National Drinking Water Contaminant Occurrence Database
National Drinking Water Advisory Council
no observed adverse effect level
National Primary Drinking Water Regulation
non-Hodgkin lymphoma
non-transient non-community water system
Office of Pesticides Programs
physiologically-based pharmacokinetic
parts per million
Public Water Systems
Quality Assurance Project Plan
Re-registration Eligibility Document
reference dose
reporting level
relative source contribution
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008
Appendix A-l
-------
SDWA Safe Drinking Water Act
SVOCs select semivolatile organic compounds
UCMR1 Unregulated Contaminant Monitoring Regulation 1
UF uncertainty factor
|J,g microgram
U.S. EPA United States Environmental Protection Agency
USGS United States Geological Service
TRI Toxic Release Inventory
VOC volatile organic compound
S-Ethyl dipropylthiocarbamate (EPTC) — January, 2008 Appendix A-2
------- |