United States
Environmental Protection
Agency
Health Effects Support
Document for Dacthal
Degradates:
Tetrachloroterephthalic Acid
(TPA) and Monomethyl
Tetrachloroterephthalic Acid
(MTP)
-------
-------
Health Effects Support Document
for
Dacthal Degradates: Tetrachloroterephthalic Acid (TPA) and Monomethyl
Tetrachloroterephthalic Acid (MTP)
U.S. Environmental Protection Agency
Office of Water (43 04T)
Health and Ecological Criteria Division
Washington, DC 20460
www.epa.gov/safewater/ccl/pdf/DacthalDegradates:TP AandMTP.pdf
EPA Document Number EPA-822-R-08-005
May, 2008
Printed on Recycled Paper
-------
Dacthal Degradates — May, 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 5 years thereafter. The following criteria are used to determine whether to
regulate a chemical on the Contaminant Candidate List:
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 the
dacthal degradates tetrachloroterephthalic acid (TPA) and monomethyl tetrachloroterephthalic
acid (MTP). To arrive at the regulatory determination, data on toxicokinetics, human exposure,
acute and chronic toxicity to animals and humans, epidemiology, and mechanisms of toxicity
were evaluated. To avoid wasteful duplication of effort, information from the following risk
assessments by the EPA and other government agencies was used in development of this
document:
U.S. EPA (United States Environmental Protection Agency). 1988b. DCPA
(Dacthal) Health Advisory. Office of Drinking Water, U.S. Environmental
Protection Agency. August, 1988.
• U.S. EPA (United States Environmental Protection Agency). 1994c. Integrated
Risk Information System (IRIS): Dacthal. Cincinnati, OH.
U.S. EPA (United States Environmental Protection Agency). 1998c.
Reregi strati on Eligibility Decision DCPA. Washington, DC: Office of Prevention,
Pesticides, and Toxic Substances (7508C), EPA738-R-98-005. November 1998.
• Michigan Department of Community Health. 2003. Health consultation: Dacthal
ground water contamination, additional toxicological data, Coloma Township,
Dacthal Degradates — May, 2008
-------
Berrien County Michigan. Prepared under a Cooperative Agreement with the
Agency for Toxic Substance and Disease Control.
Information from the published risk assessments was supplemented with information
from the primary references for key studies and recent studies of the dacthal degradates TPA and
MTP. This information was identified by a literature search conducted in 2004 and updated in
2008.
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
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 carcinogenicity assessment for the dacthal degradates TPA and MTP includes a
formal hazard identification and, when available, an estimate of tumorigenic potency. 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 the
dacthal degradates TPA and MTP 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, 1996b),
Guidelines for Neurotoxicity Risk Assessment (U.S. EPA, 1998a), Guidelines for Carcinogen
Assessment (U.S. EPA, 2005a), Recommendations for and Documentation of Biological Values
for Use in Risk Assessment (U.S. EPA, 1988a), (proposed) Interim Policy for Particle Size and
Limit Concentration Issues in Inhalation Toxicity Studies (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,
1995a), 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 dacthal degradates TPA and MTP through
potable water was developed by the Office of Ground Water and Drinking Water. It is based
primarily on first Unregulated Contaminant Monitoring Regulation (UCMR 1) data collected
Dacthal Degradates — May, 2008 vi
-------
under the SDWA. The UCMR 1 data are supplemented with ambient water data, as well as data
from the States, and published papers on occurrence in drinking water.
Dacthal Degradates — May, 2008 vii
-------
Dacthal Degradates — May, 2008 viii
-------
ACKNOWLEDGMENT
This document was prepared under the U.S. EPA contract No. 68-C-02-009, Work
Assignment No. 2-54, 3-54, and 4-54 with ICF International, Fairfax, VA. The Lead U.S. EPA
Scientist is Joyce Morrissey Donohue, Health and Ecological Criteria Division, Office of
Science and Technology, Office of Water.
Dacthal Degradates — May, 2008 ix
-------
Dacthal Degradates — May, 2008
-------
CONTENTS
FOREWORD v
ACKNOWLEDGMENT ix
LIST OF TABLES xv
LIST OF FIGURES xvii
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 3-1
3.4 Summary 3-4
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 4-7
4.3.1 Data Sources and Methods 4-7
4.3.2 Derivation of the Health Reference Level 4-7
4.3.3 Results 4-8
4.4 Summary 4-14
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 5-4
5.1.3 Intake of DCPA and DCPA Degradates (TPA and MTP) From Food . 5-5
5.2 Exposure From Air 5-5
5.2.1 Concentration of DCPA and DCPA Degradates (TPA and MTP) in Air
5-6
5.2.2 Intake of DCPA and DCPA Degradates (TPA and MTP) From Air ... 5-6
5.3 Exposure From Soil 5-7
5.3.1 Concentration of DCPA and DCPA Degradates (TPA and MTP) in Soil
5-7
5.3.2 Intake of DCPA and DCPA Degradates (TPA and MTP) From Soil . . 5-7
5.4 Other Residential Exposures 5-8
Dacthal Degradates — May, 2008 xi
-------
5.5 Occupational (Workplace) Exposures 5-8
5.5.1 Description of Industries and Workplaces 5-8
5.5.2 Types of Exposure 5-9
5.6 Summary 5-9
6.0 TOXICOKINETICS 6-1
6.1 Absorption 6-1
6.2 Distribution 6-1
6.3 Metabolism 6-2
6.4 Excretion 6-3
7.0 HAZARD IDENTIFICATION 7-1
7.1 Human Effects 7-1
7.1.1 Short-Term Studies and Case Reports 7-1
7.1.2 Long-Term and Epidemiological Studies 7-1
7.2 Animal Studies 7-1
7.2.1 Acute Toxicity 7-1
7.2.2 Short-Term Studies 7-1
7.2.3 Subchronic Studies 7-2
7.2.4 Neurotoxicity 7-3
7.2.5 Developmental/Reproductive Toxicity 7-3
7.2.6 Chronic Toxicity 7-3
7.2.7 Carcinogenicity 7-5
7.3 Other Key Data 7-6
7.3.1 Mutagenicity and Genotoxicity 7-6
7.3.2 Immunotoxicity 7-6
7.3.3 Hormonal Disruption 7-6
7.3.4 Structure-Activity Relationship 7-7
7.4 Hazard Characterization 7-7
7.4.1 Synthesis and Evaluation of Major Noncancer Effects 7-7
7.4.2 Synthesis and Evaluation of Carcinogenic Effects 7-8
7.4.3 Mode of Action and Implications in Cancer Assessment 7-8
7.4.4 Weight-of-Evidence Evaluation for Carcinogenicity 7-9
7.4.5 Potentially Sensitive Populations 7-9
8.0 DOSE-RESPONSE ASSESSMENT 8-1
8.1 Dose-Response for Noncancer Effects 8-1
8.1.1 RfD Determination 8-1
8.1.2 RfC Determination 8-2
8.2 Dose-Response for Cancer Effects 8-2
8.2.1 Choice of Study 8-3
8.2.2 Dose-Response Characterization 8-3
8.2.3 Cancer Potency and Unit Risk 8-3
Dacthal Degradates — May, 2008 xii
-------
9.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK FROM
DRINKING WATER 9-1
9.1 Regulatory Determination for Chemicals on the Contaminant Candidate List
9-1
9.1.1 Criteria for Regulatory Determination 9-1
9.1.2 National Drinking Water Advisory Council Recommendations 9-2
9.2 Health Effects 9-2
9.2.1 Health Criterion Conclusion 9-3
9.2.2 Hazard Characterization and Mode of Action Implications 9-3
9.2.3 Dose-Response Characterization and Implications in Risk Assessment
9-4
9.3 Occurrence in Public Water Systems 9-4
9.3.1 Occurrence Criterion Conclusion 9-5
9.3.2 Monitoring Data 9-5
9.3.3 Use and Fate Data 9-6
9.4 Risk Reduction 9-6
9.4.1 Risk Criterion Conclusion 9-7
9.4.2 Exposed Population Estimates 9-7
9.4.3 Relative Source Contribution 9-7
9.4.4 Sensitive Populations 9-7
9.5 Regulatory Determination Decision 9-8
10.0 REFERENCES 10-1
APPENDIX A: Abbreviations Appendix A-l
Dacthal Degradates — May, 2008 xiii
-------
Dacthal Degradates — May, 2008 xiv
-------
LIST OF TABLES
Table 2-1 Chemical and Physical Properties of Dacthal (DCPA), Tetrachloroterephthalic
Acid (TPA), and Monomethyl Tetrachloroterephthalic Acid (MTP) 2-2
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of DCPA (Dacthal)
in Ambient Surface Water, 1992-2001 4-3
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of DCPA's Mono-
acid Degradate in Ambient Surface Water, 1992-2001 4-4
Table 4-3 USGS National Synthesis Summary of NAWQA Monitoring of DCPA (Dacthal)
in Ambient Ground Water, 1992-2001 4-4
Table 4-4 USGS National Synthesis Summary of NAWQA Monitoring of DCPA's Mono-
acid Degradate in Ambient Ground Water, 1992-2001 4-5
Table 4-5 USGS National Synthesis Summary of NAWQA Monitoring of DCPA in Bed
Sediment, 1992-2001 4-6
Table 4-6 USGS National Synthesis Summary of NAWQA Monitoring of DCPA in Whole
Fish, 1992-2001 4-6
Table 4-7 Summary UCMR 1 Occurrence Statistics for DCPA Mono- and Di-acid
Degradates in Small Systems (Based on Statistically Representative National
Sample of Small Systems) 4-10
Table 4-8 Summary UCMR 1 Occurrence Statistics for DCPA Mono- and Di-acid
Degradates in Large Systems (Based on the Census of Large Systems) 4-11
Table 5-1 Anticipated Residues of DCPA, Its Metabolites, and HCB From Use of DCPA on
Food/Feed Crops as Modified From the Re-registration Eligibility Decision
Document on DCPA 5-2
Table 5-2 Estimates of Dietary Exposure to DCPA From Market Basket Survey Data . . 5-5
Table 5-3 DCPA concentrations in air samples from Jacksonville, Florida, and
Springfield/Chicopee, Massachusetts 5-6
Table 8-1 Hepatocellular Tumors in Female Sprague-Dawley Rats 8-3
Dacthal Degradates — May, 2008
xv
-------
Dacthal Degradates — May, 2008 xvi
-------
LIST OF FIGURES
Figure 2-1 Chemical structure of (a) dacthal (DCPA), (b) tetrachloroterephthalic acid (TPA),
and ©) monomethyl tetrachloroterephthalic acid (MTP) (U.S. EPA, 1998c) . . 2-1
Figure 4-1 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring — States
With At Least One Detection At or Above the MRL (1 |ig/L) 4-12
Figure 4-2 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring —
Percentage of PWSs With At Least One Detection At or Above the MRL (1 |ig/L)
4-13
Figure 4-3 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring - States
with at Least One Detection Above the HRL (>70 |ig/L) 4-14
Figure 6-1 Metabolism of DCPA 6-2
Dacthal Degradates — May, 2008 xvii
-------
Dacthal Degradates — May, 2008 xviii
-------
1.0 EXECUTIVE SUMMARY
The U.S. Environmental Protection Agency (EPA) has prepared this Health Effects
Support Document for Dacthal (DCPA) Degradates: tetrachloroterephthalic acid (TPA, or the
di-acid degradate) and monomethyl tetrachloroterephthalic acid (MTP, or the mono-acid
degradate) to assist in determining whether to regulate TPA and MTP with a National Primary
Drinking Water Regulation (NPDWR). The available data on occurrence, exposure, and other
risk considerations suggest that, because TPA and MTP do not occur in public water systems at
frequencies and levels of public health concern, regulating TPA and MTP 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 Contaminant Candidate List (CCL)
regulatory determinations.
DCPA (Chemical Abstracts Service Registry Number 1861-32-1) is a chlorinated
terephthalic acid ester that is used as a pre-emergence herbicide to control annual grasses and
some annual broad-leaved weeds. TPA (Chemical Abstracts Service Registry Number 2136-79-
0) is the terminal DCPA degradate. It is extremely mobile and persistent in the environment and
will leach to ground water wherever DCPA is used, regardless of soil properties. MTP
(Chemical Abstracts Service Registry Number 887-54-7) is a minor DCPA metabolite. No data
were found on the physical and chemical properties of TPA or MTP. The properties of both
compounds have many similarities common with the parent dacthal. Their aqueous solubility is
predicted to be higher than dacthal (0.5 mg/L at 25°C) because one or two of the ester functional
groups are replaced by a free acid functional group. For the same reason, the vapor pressures of
the acid derivatives are predicted to be lower than those for the parent (2.5 x 1CT6 mm Hg at
0.25°C).
Although there are data evaluating the parent compound's (DCPA) exposure and intake,
limited information is available to evaluate the amount of TPA or MTP present in the
environment and what the intake may be for food, air, or workplace environments. On the basis
of estimates derived from the available exposure data, it appears that food is the major source of
exposure. Further monitoring data are needed to evaluate TPA or MTP exposure and intake.
TPA and MTP are degradates of DCPA and are present only in areas where DCPA has
been used. DCPA and its derivatives have been detected in surface and ground water as well as
in public water systems. TPA and MTP combined have been detected at the health reference
level (FIRL) in no large public water systems and 0.13% of small systems, affecting 0.02% of the
population served, approximately equivalent to 113,000 individuals nationwide. DCPA, MTP,
and TPA have also been detected in ambient waters in U.S. Geological Survey (USGS) studies.
However, in all cases, concentrations have been below the FIRL and one-half the HRL (/^HRL).
Accordingly, TPA and MTP are likely to occur in public water systems but not generally at
concentrations of concern.
Both DCPA and TPA do cause adverse health effects in laboratory animals. Currently,
no toxicological studies are available to assess the toxicological effects of MTP (the mono-acid
degradate). Three studies in rats (30- and 90-day feeding studies and a developmental study) are
Dacthal Degradates — May, 2008 1-1
-------
available for TPA. The effects of exposure were mild (weight loss and diarrhea) and occurred at
doses greater than or equal to 2000 mg/kg/day. No reproductive effects were observed. The
critical effects for DCPA, the parent compound, include effects on the lung, liver, kidney, and
thyroid in male and female rats in a 2-year chronic bioassay (ISK Biotech, 1993). The available
data indicate that the adverse effects associated with TPA are much milder than those for the
parent and tend to occur at doses that are lower by approximately an order of magnitude.
No carcinogenicity studies have been performed with either TPA or MTP. Based on a
comparison of TPA toxicity with that of its parent, as well as on TPA's lack of mutagenicity, the
EPA (U.S. EPA, 2004b) concluded that TPA is unlikely to pose a cancer risk. Klopman et al.
(1996) evaluated the carcinogenic potential of TPA on the basis of its chemical and biological
properties, as well as by a variety of quantitative structure-activity relationships (QSAR) tools,
and determined that it did not present any substantial carcinogenic risk.
There is suggestive evidence that DCPA could be carcinogenic, on the basis of an
increased incidence of liver and thyroid tumors in rats and liver tumors in mice. The presence of
hexachlorobenzene and dioxin as impurities could have contributed to the cancer risk. However,
it is also possible that DCPA itself could have some tumorigenic activity. No liver or thyroid
precursor events occurred with TPA at doses of 2000 mg/kg/day for 30 days or 500 mg/kg/day
for 90 days, suggesting that it is lexicologically different from DCPA.
A reference dose (RfD) has not been set for either MTP or TPA because of the
incomplete database on these compounds. The EPA (1998c), however, suggests that the RfD for
the parent compound DCPA (i.e., 0.01 mg/kg/day) is sufficient to protect against any toxicity
from its metabolites.
Dacthal Degradates — May, 2008 1 -2
-------
2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES
Dacthal (dimethyl tetrachloroterephthalate, DCPA) is a chlorinated terephthalic acid ester
that is used as a pre-emergence herbicide to control annual grasses and some annual
broad-leaved weeds. Tetrachloroterephthalic acid (TPA, or di-acid) is the terminal hydrolytic
DCPA degradate. It is extremely mobile and persistent in the environment and will leach to
ground water wherever DCPA is used, regardless of soil properties. Monomethyl
tetrachloroterephthalic acid (2,3,5,6-tetrachloro-, monomethyl ester 1,4-benzenedicarboxylic
acid; MTP; mono-acid) is a minor DCPA metabolite (U.S. EPA, 1998c).
Currently, all registered DCPA products are in the form of single active-ingredient
formulations: emulsifiable concentrate (20.7%), flowable concentrate (54.9%), granules (1.15%-
10%), soluble concentrate/liquid (6%), wettable powder (25% and 75%), and formulation
intermediates (20.7%, 75%, and 90%). Common impurities in technical DCPA are
hexachlorobenzene (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) (U.S. EPA,
1998c). Recent changes in production have lowered the levels of impurities in commercial
Dacthal (U.S. EPA, 2004b).
Figure 2-1 Chemical structure of (a) dacthal (DCPA), (b) tetrachloroterephthalic acid
(TPA), and ©) monomethyl tetrachloroterephthalic acid (MTP) (U.S. EPA,
1998c)
Cl
The chemical structure of DCPA and of its two major metabolites, TPA and MTP, are
shown above (Figure 2-1). The physical and chemical properties and other reference
information are listed in Table 2-1. No data were found on the physical and chemical properties
of TPA or MTP. The properties of both compounds are expected to have many similarities in
common with the parent dacthal. Their aqueous solubility is predicted to be higher than dacthal,
because acids tend to be more soluble than their corresponding ethers. For the same reason, the
vapor pressures of the acid derivatives are predicted to be lower than those of the parent.
Dacthal Degradates — May, 2008
2-1
-------
Table 2-1 Chemical and Physical Properties of Dacthal (DCPA),
Tetrachloroterephthalic Acid (TPA), and Monomethyl
Tetrachloroterephthalic Acid (MTP)
Property
Chemical Abstracts Service
(CAS) Registry no.
EPA Pesticide Chemical Code
Synonyms
Registered trade name(s)
Chemical formula
Molecular weight
Physical state
Boiling point
Melting point
Specific gravity
Vapor pressure:
At 20°C
At 25°C
Partition coefficients:
Log Kow
Log Knc
Solubility in:
Water
Dioxan
Benzene
Toluene
Xylene
Acetone
Carbon tetrachloride
Conversion factors*
(at 25°C, 1 atm)
DCPA
1861-32-1
078701
Chlorthal-dimethyl,
dimethyl
tetrachloroterephthalate,
2,3,5,6-
tetrachloroterephthalic acid
dimethyl ester
Dacthal, DAC 893,
Dacthalor
C|0H6C14O4
331.97
Colorless crystals
365°C
155°C
1.70
Not identified
2.5 x 10"6mmHg
4.40
4.28
0.5 mg/L (25°C)
120 mg/L (25°C)
250 mg/L (25°C)
170 mg/L (25°C)
140 mg/L (25°C)
100 mg/L (25°C)
70 mg/L (25°C)
1 ppm =13.6 mg/m3
1 mg/m3 = 0.07 ppm
TPA
2136-79-0
078702
retrachloroterephthalic acid;
chlorothal;
perchloroterephthalic acid
Not identified
C8H2C1404
303.9134
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
1 ppm = 12.4 mg/m3
1 mg/m3= 0.08 ppm
MTP
887-54-7
Not identified
retrachloroterephthalic
acid, monomethyl-
chlorthal monomethyl,
monomethyl 2,3,5,6-
tetrachloroterephthalate
Not identified
C9H4CI4O4
317.93916
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
Not identified
1 ppm = 12.9 mg/m3
1 mg/m3 = 0.07 ppm
Source(s): ChemFinder (2004); U.S. EPA/OPP Chemical Database, Hazardous Substances Data Bank (HSDB, 2004)
*Calculated as follows: ppm = mg/m3 x (24.45/molecular weight); mg/m3 = ppm x (molecular weight/24.45).
Dacthal Degradates — May, 2008
2-2
-------
3.0 USES AND ENVIRONMENTAL FATE
3.1 Production and Use
DCPA can be produced by esterification of TPA with methyl alcohol (Spencer, 1982), by
chlorination of terephthaloyl chloride and subsequent reaction with methanol (Worthing, 1979),
or by chlorination ofp-xylene followed by conversion of the reaction products to
2,3,5,6-tetrachloroterephthaloyl chloride and finally reaction with methanol to yield the dimethyl
ester (Frear, 1976).
DCPA is used as a selective, pre-emergence herbicide to control annual grasses and some
annual broad-leaved weeds in turf, ornamentals, strawberries, certain vegetables, beans, and
cotton (U.S. EPA, 1998c). Some uses, particularly on vegetable crops, were voluntarily
terminated by the registrant in response to EPA concerns regarding the contamination of ground
water with DCPA and its di-acid degradate, TPA (U.S. EPA, 2005b). Two products, Dacthal
1.92F and 90% Dimethyl-T, produced by ISK Biotech Corporation, are the starting material
from which all other products are formulated. Today there are 66 registered products with
dacthal as an active ingredient.
There are three DCPA manufactured products registered to ISK Biosciences Corporation
(formerly Fermenta ASC Corporation): a 20.7% formulation intermediate (FI; EPA Reg. No.
50534-187), a 75% FI (EPA Reg. No. 50534-20), and a 90% FI (EPA Reg No. 50534-113).
There is also a 98% minimum technical formulation (EPA File Symbol No. 50534-ROA).
3.2 Environmental Release
TPA and MTP are not released directly into the environment. They are byproducts of
DCPA, which is a pre-emergence herbicide used for the control of annual grasses and some
annual broad-leaved weeds.
3.3 Environmental Fate
DCPA should be immobile in the soil, based on the estimated log Koc range of 3.77-3.81
(Lyman et al., 1990) and the experimental log Kow of 4.40 (Hansch et al., 1995). DCPA has been
found to adsorb onto clay and organic matter, and thus it moves minimally in the soil (Choi et
al., 1988). Volatilization from moist soil surfaces has been illustrated in published data
(Glotfelty and Schomburg, 1989; Glotfelty et al., 1984; Majewski et al., 1991); however, the
estimated Henry's law constant of 2.18 x 10~6 atm/m3/mol is low and the partitioning coefficient
is high. Nash and Gish (1989) suggested that DCPA volatilization may be adsorption and
diffusion controlled, which would explain the poor predictability of volatilization from vapor
pressure. At a temperature of 35°C, volatility accounts for the loss of most of the DCPA applied
to treated land.
In a field experiment, the loss of DCPA followed an apparent first-order dissipation rate
over 85 days after application, having a calculated soil half-life of 33.8 days. The total estimated
Dacthal Degradates — May, 2008 3-1
-------
loss by volatilization from the soil surface after 21 days was approximately 36%-52%; 26% of
the total loss was attributed to compound degradation (Majewski et al., 1991). A majority of the
loss by volatilization occurred after irrigation; when the soil surface was dry, loss was minimal
(Majewski et al., 1991). DCPA was sprayed as a 75% wettable powder onto a moist Hatboro silt
loam (23% sand, 57% silt, 20% clay, 1.2% organic matter); 2% was lost by volatilization after
34 hours and 50% was lost after 8 days (Glotfelty and Schomburg, 1989; Glotfelty et al., 1984).
DCPA's vapor pressure of 2.5 x 10~6 mm Hg and estimated Henry's law constant of 2.18
x 10~6 atm/m3/mol at 25°C indicate that it may exist in the vapor phase or particulate phase in the
atmosphere. Particulate-phase DCPA will redeposit onto the soil or water systems by wet
deposition, whereas vapor-phase DCPA may undergo photodegradation. However, DCPA is
reported to be stable to both heat and ultraviolet light (Tomlin, 1994; U.S. EPA, 1998c). In
experiments using a thin layer of DCPA on a glass plate that was exposed to sunlight for 2 to 96
hours, a 50% decrease in DCPA was observed after exposure for 5 hours, and >95%
decomposition was noted after 48 hours (HSDB, 2004). Degradation products from this study
were MTP and TPA after a 2-hour exposure; 1,2,4,5-tetrachlorobenzene was detected after
4 hours of exposure. After 64 hours, more unidentified products were noted (HSDB, 2004). The
rate constant for the vapor-phase reaction with photochemically produced hydroxyl radicals of
DCPA has been estimated as 4.41 x io~13 cm3/molecule-sec at 25°C, and the half-life was
estimated to be 36 days when the hydroxyl radical concentration is 5 x 10+5 (Meylan and
Howard, 1993).
In an early study, DCPA was stable under a sunlamp with a wavelength of 297 nm. After
the equivalent of 38.5 days of radiation on a glass bead surface, 95.7% of the applied DCPA was
present as parent DCPA. With the same sunlamp and DCPA on silica gel in the presence of a
photosensitizer (unnamed), 90.8% remained as DCPA after the equivalent of 168 days of
exposure. The primary photoproduct was MTP at 5.2% (U.S. EPA, 1998c). No
photodegradation occurred under black light and fluorescent light, which have been shown to be
similar to natural sunlight in the range of wavelengths where DCPA absorbs light (U.S. EPA,
1998c). Photodegradation may occur but is not considered a major degradation pathway for
DCPA.
Biodegradation is expected to be a major route of DCPA decay; two successive
dealkylations of the methyl groups at the ester linkages lead to the formation of MTP and TPA
(Choi et al., 1988). Both TPA and MTP were determined to be highly mobile in all soils (U.S.
EPA, 1998c); however, the organic carbon coefficient or octanol water coefficients were not
reported. Several leaching studies performed for pesticide registration or reregi strati on of DCPA
for U.S. EPA (1998c) illustrated that TPA is very mobile and more mobile in higher pH soils.
The optimal temperature and moisture conditions for the biodegradation of DCPA were
investigated in two studies (Choi et al., 1988; Wettasinghe and Tinsley, 1993). At 20-30°C and
0.2kgofH2O/kgofsoil, a half-life of 11 days was obtained (Choi et al., 1988). SoilwithO.l kg
of H2O/kg was tested at 10-15°C; the half-life was 105 days (Choi et al., 1988). The half-life
values of DCPA for coarse, medium, and fine soil textures were 44, 15, and 32 days,
respectively, at optimal temperature and moisture conditions for microbial degradation (Choi et
Dacthal Degradates — May, 2008 3-2
-------
al., 1988). The half-life for DCPA was 16.6 days in soil with a 12.6% water content at 25°C and
289 days with a 9.6% water content at 5°C (Wettasinghe and Tinsley, 1993). The MTP
degradate was quickly hydrolyzed to TPA, which was determined to be persistent because there
was no loss of the TPA metabolite over a 300-day period (Wettasinghe and Tinsley, 1993).
Measurable residues of DCPA and its two major degradates could be detected on land
that had 5 years of application (cumulative total of 94 Ib/acre) and was then untreated for 3 years
(Gershon and McClure, 1966). Radiolableled 14C-DCPA was added to soil or ground thatch,
which was then tested for parent and degradation products at 0, 1, 2, 4, 8, 12, and 16 weeks.
Thatch displayed faster degradation than did soil; in thatch, 55% and 25% dacthal remained at
4 and 16 weeks, respectively, whereas in soil, 96% and 78% dacthal remained at 4 and 16 weeks,
respectively (Hurto et al., 1979).
Sandy loam field plots were sprayed with DCPA at 4.0 kg of a.i./ha, with three replicates
in May and three replicates in October (Roberts et al., 1978). Soil residues of this herbicide
were measured at 0, 38, 63, 101, and 128 days post-application for the May spraying, at which
times 100%, 95%, 67%, 62%, and 45% of the DCPA remained, respectively (Roberts et al.,
1978). The fall applications were measured after 0, 171, and 263 days, at which times 100%,
55%, and 11% remained, respectively (Roberts et al., 1978). Horowitz et al. (1974) described
field plots that were sprayed for 4 years with DCPA (7.5 and 15.0 kg/ha per application) twice a
year, in the spring and fall. Soil samples displayed negligible phytotoxic activity following a 5-
month period after application, indicating that this herbicide is readily degraded. There was no
decrease in nitrification processes in these plots over time.
New York soil treated for 5 years with DCPA at a rate of 19 Ib/acre annually had nearly
3-times more actinomycetes in soil as compared to untreated soil (Tweedy et al., 1968).
Cultures of actinomycetes from 1 of 20 soil samples were incubated for 96 hours with dacthal
(10, 100, 1000, and 10,000 mg/L), which was the sole carbon source. The isolated
actinomycetes were able to utilize dacthal as a carbon source. Using 36Cl-labeled DCPA, it was
determined that little if any chlorine was liberated from the ring structure during microbial
degradation (Tweedy et al., 1968). Anaerobic soil conditions slowed DCPA degradation only
slightly, with estimated half-lives of 37-59 days. TPA was also the final degradate under
anaerobic conditions (U.S. EPA, 1998c).
DCPA has a water solubility of 0.5 mg/L. Since its estimated log Koc ranges from 3.77 to
3.81 and its experimental log Kow is 4.40 (Hansch et al., 1995), it is expected to bind strongly to
particulate matter and sediment in the water column (Swann et al., 1983). DCPA was stable in
water for 36 days at pH 5, 7, and 9 (U.S. EPA, 1998c). DCPA was stable to photolysis in
unbuffered water. After the equivalent of 191 exposure days (12 hours/day), less than 10% of
the parent DCPA had photolyzed (U.S. EPA, 1998c).
DCPA is expected to bioconcentrate in aquatic organisms; an estimated bioconcentration
factor (BCF) value of 1300 was obtained using an experimental log Kow of 4.40 (Hansch et al.,
1995) and a recommended regression-derived equation (Leiker et al., 1991). DCPA
bioaccumulates significantly in bluegill sunfish, having BCFs of 1894 in whole fish, 777 in
Dacthal Degradates — May, 2008 3 -3
-------
edible tissue, and 2574 in viscera. Depuration (i.e., removal of impurities from the body)
appears to be complete after 14 days. Little metabolism or degradation of DCPA occurs in fish
tissues, although there is a detectable amount of demethylation (U.S. EPA, 1998c). DCPA has
been detected in fish at several locations in the United States, providing evidence that dacthal
does bioaccumulate (DeVault, 1985; DeVault et al., 1988; Jaffe et al., 1985; Leiker et al., 1991;
Miller and Gomes, 1974; Pereira et al., 1994; Saiki and Schmitt, 1986; Schmitt et al., 1985,
1990).
3.4 Summary
DCPA is released directly into the environment during its use as a herbicide. Upon
release into the air, DCPA may exist in both the vapor and particulate phases. In the vapor
phase, it should react slowly with hydroxyl radicals with an estimated half-life of 36 days.
Particulate-phase dacthal may be removed physically from air by wet and dry deposition. DCPA
is expected to be almost completely immobile in soil, based on an estimated high Koc of 3900;
therefore, it may bind strongly to organic matter. DCPA biodegrades into MTP or TPA by
dealkylation of the methyl groups at the ester linkages. Volatilization of dacthal from moist soil
surfaces is expected on the basis of its Henry's law constant of 2.18 x 10~6 atm/m3/mol. During
a 21-day period, 36%-52% of the total measured DCPA loss from soil was accounted for by
volatilization and 26% by breakdown in soil. Photodegradation on soil surfaces may occur with
a half-life of 5 hours; reaction products include MTP, TPA, and 1,2,4,5-tetrachlorobenzene. In
water, DCPA binds strongly to particulate matter and sediment in the water column, based on its
Koc value. DCPA bioconcentrates in aquatic organisms, having an estimated BCF value of 1300,
and has been detected in fish at several locations.
DCPA's two major metabolites, MTP and TPA, are expected to be more water soluble
than the parent, because acids are more hydrophilic than methyl esters. Thus, it is expected that
these metabolites will be more mobile than the parent compound in soil. Little physical or
chemical data, however, have been presented on these compounds. TPA is unusually mobile and
persistent in the field. Data suggest that TPA will leach to ground water wherever DCPA is
used, regardless of soil properties (U.S. EPA, 1998c). TPA appears to be substantially more
persistent than parent DCPA and exhibits low soil/water partitioning. Therefore, substantial
quantities of TPA should be available for runoff for a longer period than the parent DCPA. TPA
is extremely mobile and can leach to ground water under many different conditions. Although
contrary to the data on environmental chemistry and environmental fate, which indicate that
parent DCPA would not be very mobile, it appears that under certain conditions both the DCPA
parent and the MTP metabolite can also find their way into the ground water. The persistence of
TPA in ground water is not known.
Dacthal Degradates — May, 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 DCPA,
MTP, and TPA in public water systems (PWSs). The primary source of drinking water
occurrence data was the first Unregulated Contaminant Monitoring Regulation (UCMR 1)
program. The Agency also evaluated ambient water quality data from the USGS.
4.2 Ambient Occurrence
4.2.1 Data Sources and Methods
The USGS instituted the National Water Quality Assessment (NAWQA) program in
1991 to examine ambient water quality status and trends in the United States. The NAWQA
program is designed to apply nationally consistent methods to provide a consistent basis for
comparisons among study basins across the country and over time. These occurrence
assessments serve to facilitate the interpretation of natural and anthropogenic factors affecting
national water quality. (More detailed information on the design and implementation of the
NAWQA program can be found in Leahy and Thompson [1994] and Hamilton et al. [2004].)
Study Unit Monitoring
The NAWQA program conducts monitoring and water quality assessments in significant
watersheds and aquifers referred to as "study units." The program'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). The NAWQA program monitors the occurrence of chemicals such as pesticides,
nutrients, volatile organic compounds (VOCs), trace elements, and radionuclides, as well as 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 3-5 years, alternating
with a period of less intensive research and monitoring that lasted between 5 and 7 years. Thus,
all participating study units rotated through intensive assessment in a 10-year cycle (Leahy and
Thompson, 1994). The first 10-year cycle was designated 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).
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.
Dacthal Degradates — May, 2008 4-1
-------
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 (Kolpin
and Martin, 2003; Martin et al., 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 goals 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) include only stream data. Sampling data from a single 1-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 analyzed ground water data only from wells;
data from springs and agricultural tile drains were not included. The sampling regimen used for
wells was different from 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.
The NAWQA program monitored bed sediment and fish tissue at sites considered likely
to be contaminated and at 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 Pesticide National Synthesis, USGS also analyzed the occurrence of select
semivolatile organic compounds (SVOCs) in bed sediment at sites considered likely to be
contaminated and at 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.
Over the course of Cycle 1 (1991-2001), NAWQA analytical methods may have been
improved or changed. Hence, reporting limits (RLs) varied over time for some compounds. In
the summary tables, the highest RL for each analyte is presented for general perspective. In the
Dacthal Degradates — May, 2008 4-2
-------
ground water, bed sediment, and tissue data analyses, the method of calculating concentration
percentiles sometimes varied according to 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
Surface Water and Ground Water
Under the NAWQA program, USGS monitored DCPA (listed as "dacthal") and DCPA
mono-acid degradate (listed as "dacthal monoacid") between 1992 and 2001 in representative
watersheds and aquifers across the country. Reporting limits varied but did not exceed 0.003
|ig/L for DCPA and 0.070 |ig/L for the degradate. Results for surface water and ground water
are presented in Tables 4-1, 4-2, 4-3, and 4-4.
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of DCPA
(Dacthal) in Ambient Surface Water, 1992-2001
Land Use Type
Agricultural
Mixed
Undeveloped
Urban
No. of Samples
(No. of Sites)
1890 (78)
1020 (47)
60(4)
902 (33)
Detection
Frequency (%)
11.46
15.4
6.34
21.78
50th Percentile
(Median)
Concentration
-------
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of DCPA's
Mono-acid Degradate in Ambient Surface Water, 1992-2001
Land Use Type
Agricultural
Mixed
Undeveloped
Urban
No. of Samples
(and No. of
Sites)
1233 (48)
561 (25)
19(1)
503 (18)
Detection
Frequency (%)
0.18
0.00
0.00
0.00
50th Percentile
(Median)
Concentration
-------
In ground water, DCPA detection frequencies ranged from 0% (no detectable
measurement) in undeveloped settings to 0.44% in mixed land use (major aquifer) settings,
0.96% in urban settings, and 1.18% in agricultural settings. The 95th percentile concentrations
were non-detectable in all land use settings. The highest ground water concentration, estimated
at 10 |ig/L, was found at an agricultural site (Kolpin and Martin, 2003).
Table 4-4 USGS National Synthesis Summary of NAWQA Monitoring of DCPA's
Mono-acid Degradate in Ambient Ground Water, 1992-2001
Land Use Type
Agricultural
Mixed (major
aquifer)
Undeveloped
Urban
No. of Wells
1217
1474
46
619
Detection
Frequency (%)
0.08
0.00
0.00
0.00
50th Percentile
(Median)
Concentration
-------
Table 4-5 USGS National Synthesis Summary of NAWQA Monitoring of DCPA in Bed
Sediment, 1992-2001
Land Use Type
Agricultural
Mixed
Undeveloped
Urban
No. of Sites
282
338
224
166
Detection
Frequency (%)
1.8
0.6
0.5
0.0
50th Percentile
(Median)
Concentration
-------
In whole fish, DCPA detection frequencies ranged from 1.9% in undeveloped settings to
2.0% in urban settings, 4.5% in mixed settings, and 5.0% in agricultural settings. The 95th
percentile concentrations in all settings were non-detectable. The highest concentration, 78
jig/kg wet weight, was found in an agricultural setting (Nowell, 2003).
4.3 Drinking Water Occurrence
4.3.1 Data Sources and Methods
In 1999, EPA developed the UCMR 1 program in coordination with the CCL and the
National Drinking Water Contaminant Occurrence Database to provide national occurrence
information on unregulated contaminants. EPA designed the UCMR 1 data collection with three
parts (or tiers), primarily based on the availability of analytical methods. DCPA degradates
belonged to the first tier, List 1.
List 1 assessment monitoring was performed for a specified number of chemical
contaminants for which analytical methods have been developed. With the exception of
transient non-community systems and systems that purchase 100% of their water, EPA required
all large PWSs (systems serving more than 10,000 people), plus a statistically representative
national sample of 800 small PWSs (systems serving 10,000 people or fewer) to conduct
assessment monitoring. Approximately one-third of the participating small systems were
scheduled to monitor for these contaminants during each calendar year from 2001 through 2003.
Large systems could conduct 1 year of monitoring at any time during the 2001-2003 UCMR 1
period. EPA specified a quarterly monitoring schedule for surface water systems and a twice-a-
year, 6-month interval monitoring schedule for ground water systems. Although UCMR 1
monitoring was conducted primarily between 2001 and 2003, some results were not collected
and reported until as late as 2006.
The objective of the UCMR 1 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 allocating a 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, the UCMR 1 List 1 Assessment Monitoring program
provides a contaminant occurrence data set suitable for national drinking water estimates.
4.3.2 Derivation of the Health Reference Level
To evaluate the systems and populations exposed to TPA and MTP 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 is used for chemicals that cause cancer and exhibit a linear
response to dose, and the other applies to noncarcinogens and carcinogens evaluated with a non-
linear approach. In the case of the dacthal degradates, the HRL was derived on the basis of
noncancer effects, using the RfD for the parent compound, dacthal, as follows. The basis for the
Dacthal Degradates — May, 2008 4-7
-------
calculation is detailed in Section 8.1.1. The EPA has not established an RfD for either TPA or
MTP.
HRL = 0.01 mg/kg x 70 kg x 20%
2L
HRL = 0.07 mg/L or 70 |ig/L
where
0.01 mg/kg/day = the RfD for dacthal
70 kg = adult body weight
2L/day = daily adult drinking water intake
20% = the percentage of total daily dacthal intake allocated to
drinking water
For comparison to the HRL, the total for the dacthal degradates was assumed to represent TPA,
the more stable degradate, and the concentration was back-calculated to dacthal equivalents
based on the ratio of the molecular weights for both compounds.
4.3.3 Results
As List 1 contaminants, DCPA mono- and di-acid degradates were scheduled to be
monitored by all large community water systems (CWSs) and nontransient noncommunity water
systems (NTNCWSs) and a statistically representative sample of small CWSs and NTNCWSs.
The data presented in this report reflect UCMR 1 analytical samples submitted and quality-
checked under the regulation as of March 2006. DCPA degradate data were collected and
submitted by 797 (99.6 percent) of the 800 small systems selected for the small system sample
and 3079 (99.3 percent) of the 3100 large systems defined as eligible for the UCMR 1 large
system census. Because the analytical method approved for UCMR 1 use does not distinguish
between the two degradates, they are measured and reported in aggregate. The DCPA degradate
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 HRL (>HRL or >70 |ig/L), and exceedances of
one-half the value of the HRL (>!/2HRL or >35 |ig/L). Results of these analyses are presented in
Tables 4-7 and 4-8.
Among small systems, DCPA degradate detections (>MRL or > 1 |ig/L) were reported by
2.13% of PWSs, representing 3.19% of the population served, equivalent to approximately 1.1
million people nationally. All but one of these systems was served by ground water. Only a
single small system had a concentration >/^HRL (>35 |ig/L), and >HRL (>70 |ig/L); this ground
water system represented 0.13% of small PWSs and 0.02% of the population served by them,
equivalent to 113,000 persons nationally.
Among large systems, 160 systems (5.20%) had detections >MRL (>1 |ig/L), affecting
approximately 11.3 million people (5.07% of the population served). Most of these were ground
Dacthal Degradates — May, 2008 4-8
-------
water systems. A single large system had a concentration >/^HRL ( >35 |ig/L); this surface
water system represented 0.03% of large PWSs and 0.33% of the population served by them
(approximately 738,000 people). No large systems had detections at concentrations >HRL (>70
Dacthal Degradates — May, 2008 4-9
-------
Table 4-7 Summary UCMR 1 Occurrence Statistics for DCPA Mono- and Di-acid
Degradates in Small Systems (Based on Statistically Representative National
Sample of Small Systems)
Frequency Factors
Total Number of Samples
Percent of Samples with Detections
99l Percentile Concentration (all samples)
Health Reference Level (HRL)
Minimum Reporting Level (MRL)
Maximum Concentration of Detections
99l 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 with Detections (> MRL)
GW PWSs with Detections
SW PWSs with Detections
PWSs > 1/2 HRL
GW PWSs > 1/2 HRL
SW PWSs > 1/2 HRL
PWSs > HRL
GW PWSs > HRL
SW PWSs > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Pop. Served by GW PWSs with Detections
Pop. Served by SW PWSs with Detections
Population Served by PWSs > 1/2 HRL
Pop. Served by GW PWSs > 1/2 HRL
Pop. Served by SW PWSs > 1/2 HRL
Population Served by PWSs > HRL
Pop. Served by GW PWSs > HRL
Pop. Served by SW PWSs > HRL
UCMR Data -
Small Systems
3,272
1.16%
1.3 ug/L
70 ug/L
lug/L
190 ug/L
190 ug/L
1.8 ug/L
797
590
207
2,760,570
1,939,815
820,755
Number
17
16
1
1
1
0
1
1
0
87,933
86,433
1,500
500
500
0
500
500
0
Percentage
2.13%
2.71%
0.48%
0.13%
0.17%
0.00%
0.13%
0.17%
0.00%
3.19%
4.46%
0.18%
0.02%
0.03%
0.00%
0.02%
0.03%
0.00%
National System &
Population Numbers
--
--
--
--
--
--
--
--
60,414
56,072
4,342
45,414,590
36,224,336
9,190,254
National Extrapolation
689
652
37
373
373
0
373
373
0
1,118,000
1,074,000
44,000
113,000
113,000
0
113,000
113,000
0
1. Total PWS and population numbers are from EPA September 2004 Drinking Water Baseline Handbook, 4th edition.
2. National extrapolations are generated separately for each population-served size stratum and then added to yield the national estimate of GW
PWSs with detections (and population served) and SW PWSs with detections (and population served). For intermediate calculations at the level
of individual strata, see EPA's UCMR 1 Occurrence Report, entitled "The Analysis of Occurrence Data from the First Unregulated Contaminant
Monitoring Regulation (UCMR 1) in Support of Regulatory Determinations for the Second Drinking Water Contaminant Candidate List."
Abbreviations and terms:
PWS = public water systems; GW = ground water; SW = surface water; N/A = not applicable; total number of samples = the total number of
samples on record for the contaminant; 99th percentile concentration = the concentration in the 99th percentile sample (out of either all samples
or just samples with detections); median concentration of detections = the concentration in the median sample (out of samples with detections);
total number of PWSs = the total number of PWSs for which sampling results are available; total population served = the total population served
by PWSs for which sampling results are available; PWSs with detections, PWSs >'/2HRL, or PWSs >HRL = PWSs with at least one sampling
result greater than or equal to the MRL, exceeding the '/zHRL 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 '/2HRL 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.
Dacthal Degradates — May, 2008
4-10
-------
Table 4-8 Summary UCMR 1 Occurrence Statistics for DCPA Mono- and Di-acid
Degradates in Large Systems (Based on the Census of Large 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
99 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 with Detections (> MRL)
GW PWSs with Detections
SW PWSs with Detections
PWSs > 1/2 HRL
GW PWSs > 1/2 HRL
SW PWSs > 1/2 HRL
PWSs > HRL
GW PWSs > HRL
SW PWSs > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Pop. Served by GW PWSs with Detections
Pop. Served by SW PWSs with Detections
Population Served by PWSs > 1/2 HRL
Pop. Served by GW PWSs > 1/2 HRL
Pop. Served by SW PWSs > 1/2 HRL
Population Served by PWSs > HRL
Pop. Served by GW PWSs > HRL
Pop. Served by SW PWSs > HRL
UCMR Data -
Large Systems
30,638
2.41%
ViHRL, 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 >'/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.
Dacthal Degradates — May, 2008
4-11
-------
Regional Patterns
The geographic distribution for systems with at least one sample that exceeded the MRL
(Figures 4-1 and 4-2) was examined to evaluate whether there was a regional pattern to the
occurrence of the dacthal degradates in public drinking water supplies.
Figure 4-1 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring ~
States With At Least One Detection At or Above the MRL (1 ug/L)
D Guam D Mariana Is.
D Virgin Is. D Puerto Rico
D Tribes
Q Entities with No Detections
[~] Entities with Detections (> 1 ug/L)
Dacthal Degradates — May, 2008
4-12
-------
Figure 4-2 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring ~
Percentage of PWSs With At Least One Detection At or Above the MRL (1
Hg/L)
PID
• Guam D Mariana Is.
D Virgin Is. D Puerto Rico
D Tribes
Note: This map depicts UCMR 1 results from both small systems and large systems. The statistical
selection of UCMR 1 small systems was designed to be representative at the national level, but not at the
state level. Therefore, this map should only be considered a rough approximation of state-level patterns of
contaminant occurrence.
The dacthal degradates were detected in various states across the country. The highest
concentrations of detections (15.1%-42% of PWSs) were seen in Arizona, Delaware, Nebraska,
New Jersey, Rhode Island, and Guam. There appeared to be a cluster of states with detections
that ranged from 5.01% to 15% of samples in the Northeast and the states surrounding the Great
Lakes. The only state with a detection that exceeded the HRL was Michigan (Figure 4-3).
Dacthal Degradates — May, 2008
4-13
-------
Figure 4-3 Geographic Distribution of DCPA Degradates in UCMR 1 Monitoring
States with at Least One Detection Above the HRL (>70 ug/L)
V r
Guarti
'Jttgtn b
Tnbos
Puerto Rrco
4.4 Summary
TPA and MTP are degradates of DCPA and are present only in areas where DCPA has
been used. DCPA and/or its derivatives have been detected in ambient surface and ground water
(DCPA and MTP), as well as in public water systems (MTP and TPA combined). TPA and
MTP combined were not detected at the HRL in any large systems. They were found at levels
exceeding the HRL in 0.13% of small systems, affecting 0.02% of the population served by
small systems, approximately equivalent to 113,000 individuals nationwide. MTP was detected
at a maximum concentration of 0.430 |ig/L (median and 95th percentile concentrations were
below the reporting level) in ambient surface waters near agricultural use but was not detected in
ambient surface waters near mixed, undeveloped, or urban areas. MTP was detected at a
maximum concentration of 1.1 |ig/L (median and 95th percentile concentrations were below the
reporting level) in ambient ground waters near agricultural use but was not detected in ambient
surface waters near mixed, undeveloped, or urban areas. DCPA also has been measured in
sediment, but there are no data available on TPA or MTP levels in sediment. TPA and MTP,
however, have been determined to be more mobile in soil than the parent compound, DCPA.
Dacthal Degradates — May, 2008
4-14
-------
5.0 EXPOSURE FROM MEDIA OTHER THAN WATER
5.1 Exposure From Food
5.1.1 Concentration in Non-Fish Food Items
Data were not available on the degradates MTP or TPA in foods. Most of the
information is provided for DCPA or total DCPA, which combines degradate and parent
compound data.
Plant residue analyses were submitted to the Office of Pesticides Programs (OPP) for
reregistration of dacthal (DCPA) (U.S. EPA, 1998c). The analysis had limits of detection (LOD)
of 0.01 parts per million (ppm) each for DCPA, MTP, and TPA. The plants analyzed were
potatoes (including processed commodities), sweet potatoes, broccoli, celery, cucumbers, green
and bulb onions, strawberries, sweet and bell peppers, cantaloupes, tomatoes (including
processed commodities), summer squash, and processed commodities of beans and cottonseed
(U.S. EPA, 1998c). A second, similar method was used to detect DCPA, MTP, and TPA in milk
and beef fat (U.S. EPA, 1998c). Use of DCPA on beans, peppers, and squash has been
terminated (U.S. EPA, 2005b), removing the residue concern for these crops in the future.
In 1963, a cattle feeding study was performed in which DCPA was fed to cattle at levels
of 20 and 200 ppm. At the 20-ppm feeding level, combined residues of DCPA, MTP, and TPA
were non-detectable in milk and fat. Muscle, liver, and kidney were not analyzed (U.S. EPA,
1998c). Further studies performed in a goat metabolism study indicated that a cattle feeding
study is needed.
In 1973, poultry feeding studies were conducted. Chickens were fed 4- and 40-ppm
DCPA for 30 days, and residue analyses for DCPA, MTP, and TPA were conducted. In hens fed
4 ppm, all residues were non-detectable in edible tissues, but at the 40-ppm level, detectable
combined residues were observed only in fat at 0.14 ppm. Combined residues in egg yolk at the
4-ppm feeding level were 0.07 ppm on day 21 of the study. The animals given 40 ppm had 0.26
ppm in egg yolk residues after 21 days.
The values in food products in Table 5-1 are anticipated residues of DCPA, MTP, and
TPA, not actual monitoring data. The data represented in Table 5-1 were derived from actual
studies or calculated estimations of residues in food products from registrant field trials and
processing studies, from monitoring data supplied by the U.S. Food and Drug Administration
(FDA), and from survey data supplied by the U.S. Department of Agriculture (USD A) (U.S.
EPA, 1998c). The limit of detection was 0.1 ppm for DCPA, MTP, and TPA for plant
commodities analyzed by a gas chromatography/electron capture (GC/EC) method. Another
GC/EC method, similar to those submitted for plants, is available for determining DCPA, MTP,
and TPA in milk and beef fat; the LOD was 0.01 ppm (U.S. EPA, 1998c).
Dacthal Degradates — May, 2008 5-1
-------
Table 5-1 Anticipated Residues of DCPA, Its Metabolites, and HCB From Use of
DCPA on Food/Feed Crops as Modified From the Re-registration Eligibility
Decision Document on DCPAa
Food Name
Peppers, other
Chili peppers
Pimentos
Tomatoes, whole
Tomatoes, juice
Tomatoes, puree
Tomatoes, paste
Tomatoes, catsup
Broccoli
Brussels sprouts
Cauliflower
Cabbage, green/red
Collards
Kale
Kohlrabi
Lettuce, leafv varietiesa'b
Lettuce, unspecifieda'b
Mustard sreensa
Turnip' tops
Cress, upland
Lettuce-head varietiesa'b
Garlic
Leeks
Onions-dry bulb (cipollini)
Potatoes, whole
Potatoes, peeled
Radishes, roots
Radishes, tops
Rutabagas, roots"
Shallots
Sweet potatoes (including yams)
Turnip, roots
Corn, pop"
Beans-succulent, lima
Beans, dry
Black-eyed peas, dry
Onions, green
Cottonseed, oil
Cottonseed, meal
Soybeans-mature, seeds dry"
Milk, nonfat solids
Milk, fat solids
Residue Data Source
DCPA
Field trials
Field trials
Field trials
Field trials
Processing study
Processing study
Processing study
Processing study
Field trial
Field trials
Brussels sprouts data
Field trials
Kale data
Field trials
Brussels sprouts data
FDA monitoring
FDA monitoring
Field trials
Field trials
Field trials
FDA monitoring
Onion data
Field trials
Field trials
Field trials
Field trials
Field trials
Field trials
Tolerance
Field trials
Field trials
Field trials
Tolerance
Field trials
Field trials
Field trials
Field trials
Field trial
Tolerance
Goat metabolism study
Anticipated Residues
(ppm)
DCPA, MTP,
andTPA
0.17
0.17
0.17
0.11
0.11
0.15
0.396
0.12
0.1
0.04
0.04
0.35
0.5
0.5
0.04
0.65
0.65
1
0.775
0.36
0.65
0.02
0.57
0.02
0.25
0.25
0.07
9.12
2
0.57
0.64
0.275
0.05
0.26
0.09
0.36
0.57
0.02
2
0.0000006
Dacthal Degradates — May, 2008
5-2
-------
Food Name
Milk sugar (lactose)
Beef, goat, sheep, pork-meat byproducts
Beef, goat, sheep, pork (organ meats)-other
Beef, dried
Beef, soat sheep, pork (boneless)-fat
Beef, goat, sheep, pork (organ meats)-kidney
Beef, goat, sheep, pork (organ meats)-liver
Beef, goat, sheep, pork (boneless)-lean (without
removable fat)
Turkey, other poultry, chicken-by-products
Turkey, other poultry, chicken-siblets (liver)
Turkey, chicken-flesh (without skin, without
bones)
Turkey, other poultry, chicken-flesh (with skin,
without bones)
Turkey, unspecified
Eggs, whole (36.55 yolk)
Eggs, white only
Eggs, yolk only
Residue Data Source
DCPA
Goat
metabolism study
Poultry feeding study
Anticipated Residues
(ppm)
DCPA, MTP,
andTPA
0.0000011°
0.0000017
0.0000006
0.0000011
0.0000057
0.0000017
0
0.0000230°
0
0
0.0000230°
0.0000230°
0.0000011
0.0000009
0.0000138
Source: U.S. EPA (1998c)
a The residue values for these crops are based on FDA monitoring or USDA survey data and were not adjusted for
the percentage of crop treated in the Dietary Risk Evaluation System analysis, the system EPA's OPP uses to
calculate carcinogenic and chronic, noncarcinogenic risk of DCPA for all raw agricultural commodities in which
DCPA tolerances have been established.
b There are no established uses on this crop; however, the registrant has expressed an interest in retaining a tolerance
to cover potential residues from rotation of this crop into fields that have been previously treated with DCPA. The
tolerance on this crop and anticipated residues will be reassessed in conjunction with review of rotational crop
studies and registrant proposals for inadvertent residue tolerance and rotational crop restrictions on DCPA labels.
Other crops of concern are sweet corn; corn grain, endosperm; corn grain, bran; corn sugar; corn grain, oil;
soybeans, oil; soybeans, unspecified; and soybean, flour.
c The anticipated residue on this food is assumed to be the same as for fat.
Produce samples from 1989-1990 were tested for the presence of DCPA (n = 6970;
approximately 80% domestic, 20% foreign); the detection limit was 0.125 ppm, and 50 samples
were positive for DCPA. DCPA was detected in broccoli samples (n = 203; 2.5% incidence),
greens (n = 153; 1.3%), lettuce (1.3%), onions (1.2%), and turnips (n = 44; 9.0%) (Schattenberg
and Hsu, 1992). In the 1982-1984 Market Basket Study, DCPA residues were found in 2% of
the total samples (n > 3000) (Gunderson, 1988). In the 1980-1982 Market Basket Study (27
locations) for adult diets, DCPA was detected in 9 samples of leafy vegetables (trace = 0.057
ppm), 12 samples of root vegetables (trace = 0.004 ppm), and 2 samples of garden fruits (trace =
0.002 ppm) (Gartrell et al., 1986a). Market Basket studies for 1974-1980 for adult diets detected
DCPA in 11 samples of leafy vegetables (trace = 0.017 ppm), 7 samples of root vegetables (trace
= 0.002 ppm), 9 samples of garden fruits (trace = 0.008 ppm), and 2 samples of oils/fats (0.002-
Dacthal Degradates — May, 2008
5-3
-------
0.004 ppm) (Gartrell et al., 1985a, 1985b; Johnson et al., 1977, 1981, 1984). Detection limits
were not specified in secondary literature for most of the studies cited in this paragraph. In the
1991-2001 Total Dietary Study, dacthal residues were detected in a variety of produce. The
most frequent detections were found in leafy vegetables (spinach and collard greens) and root
vegetables (radish and turnip). Green beans had a low incidence of detection but relatively high
mean concentrations, whereas black olives had a high frequency of detection but a low average
residue level (U.S. FDA, 2003).
5.1.2 Concentrations in Fish and Shellfish
Data were not available on the degradates MTP or TPA; all data were for DCPA or
DCPA and degradates combined as total DCPA residues.
Tissue samples of catfish were collected along the Mississippi River and several major
tributaries during July and August 1987 and analyzed for DCPA; catfish from Winfield,
Missouri, to Chester, Illinois, had DCPA residues at concentrations ranging from 0 to 9 ng/g wet
weight (Leiker et al., 1991). In another study, mature striped bass were taken from the
Sacramento and the San Joaquin Rivers and analyzed for DCPA in May 1992 (n = 7); the levels
were <0.1-8.7 ng/g wet weight (Pereira et al., 1994). Bluegill and carp were collected from the
San Joaquin River, Merced River, and Salt Slough in California. Bluegills from four sites had
DCPA concentrations of 0-0.01 mg/kg wet weight, and carp were 0-0.054 mg/kg wet weight
(detection limit = 0.004 mg/kg) (Saiki and Schmitt, 1986). DCPA was analyzed in samples of
spotted sea trout, perch, speckled trout, mullet, red drum, and menhaden collected from the Rio
Grande River in Texas from 1971 to 1972, which had residue levels of 0-555 parts per billion
(ppb) (Miller and Gomes, 1974). Great Lakes harbors and tributaries were tested for DCPA in a
composite sampling of indigenous fish; 73% had detectable DCPA levels that ranged from 0.002
to 0.12 mg/kg (DeVault, 1985).
DCPA was detected in fish that were sampled via the National Contaminant
Biomonitoring Program, in which composite fish samples are analyzed from 112 stations in
major rivers and the Great Lakes in the United States. The percentages of samples with
detections were as follows: 1978-1979, 34.3%; 1980-1981, 28%; and 1984, 45.5% (Schmitt et
al., 1990). Between 1978 and 1979, DCPA measures were a maximum wet weight of 1.22 |ig/g
and 18.8 |ig/g lipid weight; in 1980-1981, maximum wet weight was 0.40 |ig/g wet weight and
6.1 ng/g lipid weight (Schmitt et al., 1985). Carp from major tributaries and embayments of
Lake Superior and Lake Huron were analyzed for the presence of DCPA; the total composite
concentration range was 2.2-17 ng/g fish fat (Jaffe et al., 1985). Carp from the mouths of
tributaries to Lake Ontario and the Niagara River were analyzed for the presence of DCPA; the
total composite concentration range was 93-2300 ng/g fish fat (Jaffe and Kites, 1986). Fall-run
coho salmon from each of the Great Lakes were analyzed for DCPA, and the concentrations
ranged from not detected at five sites to <0.05 ng/g at nine sites (DeVault et al., 1988).
Dacthal Degradates — May, 2008 5-4
-------
5.1.3 Intake of DCPA and DCPA Degradates (TPA and MTP) From Food
Data were not available on the intake of MTP or TPA from the diet; data were provided
as DCPA or total DCPA, which combined degradate and parent compound.
Data are available from several market basket surveys in which DCPA or DCPA and
degradates in the diet were examined. In market basket surveys, foods are purchased from local
suppliers and prepared as served. They are then analyzed for a variety of nutrients, pesticides,
and/or xenobiotic compounds. Data are presented as either intakes for age/sex populations
groupings and/or concentration in selected food groupings. The data for population groupings
are summarized in Table 5-2.
Table 5-2 Estimates of Dietary Exposure to DCPA From Market Basket Survey Data
Survey Date
1976-1977
1978
1979
1980-1982
1982-1984
Population Group
Infant
(ng/kg)
20
2
NDb
1.9
Child
(ng/kg)
1
1
ND-1
2.4
Adolescent
(ng/kg)
2
1.2-1.9
Adult
(ng/kg)
1.1
2.1a
2.4a
1.1-1.8
Reference/Notes
Johnson et al., 1984
Gartrelletal., 1986a; 13 locations
Gartrell et al., 1985a, 1985b
Gartrelletal., 1986a, 1986b
Gunderson, 1988; 24 states
a Authors reported 145 ng/day in 1979 and 165 ng/day in 1980-1982. Assuming an average body weight of 70 kg gives the
ng/kg presented in the table.
b ND = none detected.
A market basket survey performed in 27 locations during October 1980 to March 1982
reported the data for DCPA in adult foods as 0.137 ng/day from leafy vegetables, 0.0213 ng/day
in root vegetables and 0.007 ng/day from garden fruits (Gartrell et al., 1986a, 1986b). The
average daily intake of DCPA from October 1979 to July 1980 in adult foods was 0.0920 |ig/day
from leafy vegetables, 0.005 |ig/day from root vegetables, and 0.0476 |ig/day from garden fruits
(Gartrell et al., 1985a, 1985b). Detection limits were not specified in secondary literature for
most of the studies cited in this section. In both sets of data, the leafy vegetables seemed to
provide the major exposures to DCPA.
5.2 Exposure From Air
Data were not available on the degradates MTP or TPA; most data were provided as
DCPA or total DCPA, which combined degradate and parent compound data.
Nonoccupational exposure results from the inhalation of both indoor and outdoor air,
particularly near agricultural areas (Tessari and Spencer, 1971; Whitmore et al., 1994; Lee,
1977; Kutz et al., 1976), and carpet dust (Starr et al., 1974; Lewis et al., 1994). Spray drift
droplet spectrum analysis was not required by EPA because the pesticide producer was a
Dacthal Degradates — May, 2008
5-5
-------
participant in the Spray Drift Task Force. Spray drift is assumed to be 5% of the application rate
(U.S. EPA, 1998c).
5.2.1 Concentration of DCPA and DCPA Degradates (TPA and MTP) in Air
Data were not available on the degradates MTP or TPA; most data were provided as
DCPA or total DCPA, which combined degradate and parent compound data.
Indoor and outdoor air samples collected monthly for 1 year at homes of occupationally
exposed men in Colorado showed the presence of DCPA at similar concentrations for all
conditions: farmers indoor, incidence = 31/38, range = 0.08-12.04 |ig/m3; farmers outdoor,
incidence = 31/37, range = 0.02-9.12 |ig/m3; formulators indoor, incidence = 48/52, range =
0.05-8.72 |ig/m3; formulators outdoor, incidence = 39/54, range = 0.08-38.26 |ig/m3 (Tessari and
Spencer, 1971).
Indoor, outdoor, and personal air samples were collected in winter, spring, and summer
in Jacksonville, Florida, and Springfield/Chicopee, Massachusetts, to assess nonoccupational
exposure to DCPA. Residents from Jacksonville had low exposures, and the
Springfield/Chicopee residents were exposed to higher levels of DCPA (see Table 5-3)
(Whitmore et al., 1994). The arithmetic mean airborne pesticide concentration of DCPA in the
United States in 1970-1971 equaled trace levels of this compound; 0.49% of the samples were
positive, and the maximum DCPA value was 2.1 ng/m3 (Lee, 1977; Kutz et al., 1976).
Table 5-3 DCPA concentrations in air samples from Jacksonville, Florida, and
Springfield/Chicopee, Massachusetts
Season
Winter
Spring
Summer
Concentration (ng/cm3)
Jacksonville, FL
Indoor Air
0.3
ND
0.2
Outdoor
Air
ND
ND
ND
Personal Air
0.2
ND
0.6
Springfield/Chicopee, MA
Indoor
Air
0.3
1.6
—
Outdoor Air
ND
0.9
—
Personal
Air
0.3
2.6
—
ND = not detected.
— = not measured.
5.2.2 Intake of DCPA and DCPA Degradates (TPA and MTP) From Air
Estimates of nonoccupational exposures to DCPA for adults can be derived from the
arithmetic mean ambient air concentration in 1970-1971 (Lee, 1977; Kutz et al., 1976), using the
assumption that adult humans breathe 15.2 m3 of air per day (U.S. EPA, 1996a).
2.1 ng/m3 x 15.2 m3/day = 31.92 ng/day, rounded to 32 ng/day
Dacthal Degradates — May, 2008
5-6
-------
For children, the average rate for air exchange is 8.7 m3/day, giving an exposure of
2.1 ng/m3 x 8.7 m3/day =18.27 ng/day, rounded to 18 ng/day
The concentration in air reported by Whitmore et al. (1994) for Jacksonville, Florida, and
Springfield/Chicopee, Massachusetts, indicates that ambient air exposures are often less than the
estimate derived from the 1970-1971 data. Individual intakes vary depending on factors
including activity, geographic location, and inhalation rate.
5.3 Exposure From Soil
5.3.1 Concentration of DCPA and DCPA Degradates (TPA and MTP) in Soil and
Sediment
Data were not available on the degradates MTP or TPA; most data were provided as
DCPA or total DCPA, which combined degradate and parent compound data.
In sediment samples taken in 1986 from the Moss Landing drainage area in California,
12% contained DCPA. The concentration ranged from not detected to 25-|ig/kg dry weight,
where the detection limit was 8.8 |ig/kg (Fleck et al., 1988).
DCPA was detected in 39% of the soil samples from the Moss Landing drainage area.
Concentrations ranged from not detected to 690-|ig/kg dry weight. Of the samples taken from
the Salinas and Carmel River Valley agricultural areas, 47% had a range of not detected to 700-
|ig/kg dry weight (detection limit, 4.4 |ig/kg) (Fleck et al., 1988). In 1972, 1533 sites in 37 states
had soil samples tested for DCPA; only 0.1% of the total samples had DCPA detected at a
concentration of 0.18 ppm (Carey et al., 1979).
5.3.2 Intake of DCPA and DCPA Degradates (TPA and MTP) From Soil
Human exposure to contaminants in soils is usually from dust that infiltrates homes,
automobiles, etc., in adults and from dust 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, 1996a). Using the data from Carey et al. (1979) of 0.18 mg/kg soil and the
assumption that infants ingest 0.0001 kg (100 mg) of soil per day, the exposure to DCPA from
soil would be about 20 ng/day for infants and 9 ng/day for adults.
0.18 mg/kg of soil x 0.0001 kg of soil = 0.000018 mg (18 ng)/day
0.18 mg/kg of soil x 0.00005 kg of soil = 0.000009 mg (9 ng)/day
DacthalDegradates — May, 2008 5-7
-------
5.4 Other Residential Exposures
Data were not available on the degradates MTP or TPA; most data were provided as
DCPA or total DCPA, which combined degradate and parent compound data.
Household dust samples from Colorado showed the presence of DCPA as follows:
control group, incidence = 14/182, mean concentration = 7.11 ppb; farmers, incidence = 22/45,
mean = 18.50 ppb; formulators, incidence = 19/95, mean = 7.28 ppb (Starr et al., 1974). DCPA
was detected in carpet dust in two of nine houses in the Raleigh-Durham-Chapel Hill area, North
Carolina (Lewis et al., 1994).
5.5 Occupational (Workplace) Exposures
Data were not available on the degradates MTP or TPA; most data were provided as
DCPA or total DCPA, which combined degradate and parent compound data. DCPA was
detected in the hand rinses from 2 of 11 people who were occupationally exposed to the
herbicide. DCPA was detected up to 112 days after exposure (Kazen et al., 1974).
5.5.1 Description of Industries and Workplaces
DCPA is applied with tractor-mounted boom sprayers, tractor-drawn granular spreaders,
shaker cans, and residential push-type and "whirly-bird" spreaders, and by aerial application
(U.S. EPA, 1998c). Based on use patterns, the following 10 major exposure scenarios were
identified for DCPA (U.S. EPA, 1998c):
1. Mixing/loading:
a. of liquid flowable formulation
b. of wettable powder formulations
2. Mixing and loading granular product for ground applications
3. Aerial application
a. of liquid formulation
b. of granul ar product
4. Applying the liquid and wettable powders with groundboom equipment
5. Applying with a granular spreader cultivator mounted
6. Flagger exposure:
a. to liquids
b. to granulars
7. Applying with a shaker can
8. Applying with a backpack
9. Mixing/loading and applying with a residential push-type spreader
10. Mixing/loading and applying with a whirly-bird spreader
All exposure patterns assume that workers wore long pants, long-sleeved shirts, and protective
gloves.
DacthalDegradates — May, 2008
-------
5.5.2 Types of Exposure
Dermal and inhalation exposures are expected among agricultural and horticultural
professionals who work with DCPA. The extent of the exposure will depend on how DCPA is
used and applied.
5.6 Summary
There are data evaluating the parent compound's (DCPA's) exposure and intake, but
limited information is available to evaluate the amount of TPA or MTP present in the
environment and what the intake may be for food, air, or workplace environments. On the basis
of estimates derived from the available exposure data, it appears that food is the major source of
exposure. Further monitoring data are needed to evaluate TPA or MTP exposure and intake.
DacthalDegradates — May, 2008 5-9
-------
DacthalDegradates — May, 2008 5-10
-------
6.0 TOXICOKINETICS
TPA and MTP are metabolites and environmental degradates of dacthal (DCPA).
However, there is little information on the toxicokinetics of either compound.
6.1 Absorption
Although there have been no oral absorption studies on TPA or MTP, studies indicate
that the parent compound DCPA is poorly absorbed. In humans, at least 6% of a 25-mg dose
and 12% of a 50-mg dose were determined to be absorbed, as indicated by the presence of
metabolites in the urine (Tusing, 1963).
Dogs were determined to excrete 97% of a single dose of DCPA (capsules containing
100 or 1000 mg/kg) as the parent compound in the feces by 96 hours, indicating lack of
absorption (Skinner and Stallard, 1963). Approximately 3% of dacthal was converted to MTP.
Two percent was eliminated in the urine and 1% in the feces. Less than 1% (0.07%) of DCPA
was converted to TPA, which was also excreted in the urine.
Radiolabeled DCPA was given to a lactating goat to determine absorption and
distribution in a ruminant species. After dietary exposure to a concentration of 10 ppm for
4 days, radiolabel was detected in the tissues, indicating that absorption had occurred. Tissue
residues accounted for 38.5% of the dose, suggesting that a minimum of this amount was
absorbed (U.S. EPA, 1998c).
No studies are available on inhalation or dermal absorption of either TPA or MTP.
6.2 Distribution
No studies on the distribution of TPA or MTP after oral exposure are available. DCPA
containing 1.1% MTP and 1.7% TPA was not found in the liver, kidneys, or adipose tissues of
dogs treated with 10,000 ppm (250 mg/kg-day) in the diet for 2 years (Skinner and Stallard,
1963). After a single dose of 100 or 1000 mg of DCPA per kg was given to dogs, TPA was
detected in kidney and MPA was found in kidney, liver, and adipose tissue. Some DCPA was
also found in adipose tissue.
Processing of dietary components in ruminants can differ from that in other species.
After a lactating goat was exposed to a concentration of 10-ppm radiolabeled DCPA for 4 days,
tissue levels accounted for 38.5% of the dose, and 80%-98% was present as MTP (U.S. EPA,
1998c). Residue concentrations were highest in kidney (0.1007 ppm), followed by liver (0.0333
ppm), fat (0.0168-0.179 ppm), and muscle (0.0057-0.107 ppm). Deposits in fat were the only
ones that contained the DCPA parent compound; in fat, DCPA was 10%-15% of the total
residue.
Dacthal Degradates — May, 2008 6-1
-------
Some of the radiolabel (0.01 ppm) given to the lactating goat was found in the milk,
indicating that DCPA or its metabolites are transferred to mammary secretions. The specific
radiolabeled compound or compounds present in the milk were not identified (U.S. EPA, 1998c).
No studies are available on the distribution of TPA, MTP, or DCPA after inhalation or
dermal exposure.
6.3 Metabolism
No studies are available on the metabolism of either TPA or MTP. Some animals excrete
TPA and/or MTP as metabolites of DCPA, suggesting that dacthal is converted to the mono- and
di-acid derivatives (U.S. EPA, 1998c; Skinner and Stallard, 1963; Tusing, 1963). Some of this
probably occurs in the gastrointestinal tract by way of nonspecific esterases; additional
hydrolysis may also occur in the liver and other tissues. Hydrolysis would be a two-step
process, as indicated in Figure 6-1. Based on the metabolism of other phthalate esters, MPA is
more likely formed in the gastrointestinal tract and TPA in the tissues. The identification of
TPA as the terminal metabolite of DCPA is supported by the results of using the META
metabolism and biodegradation expert system to predict the aerobic metabolism of DCPA. The
META system predicted that, once formed, TPA is stable to further degradation (Klopman et al.,
1996).
Figure 6-1 Metabolism of DCPA
out.
c
CH , OH CH 3 OH
Tusing (1963) reported that humans who took single oral doses of pure DCPA (25 or 50
mg) converted 3-4% of the dose to MTP within 24 hours. After 3 days, approximately 6% of the
25-mg dose and 11% of the 50-mg dose were converted to MTP. At both doses, less than 1%
was converted to TPA in the 1- or 3-day period. The low levels of metabolites in relation to dose
are, at least in part, a reflection of the limited absorption of DCPA. Skinner and Stallard (1963)
and Hazleton and Dieterich (1963) reported that, in dogs administered single oral doses of
DCPA, small amounts were converted to MTP (3%) and TPA (0.07%). The Skinner and
Stallard (1963) study was a single-dose study, and the Hazleton and Dieterich (1963) study was a
long-term study.
Dacthal Degradates — May, 2008 6-2
-------
6.4 Excretion
Few studies are available on the excretion of TPA or MTP. In human studies (Tusing,
1963), 6% of a single 25-mg oral dose was excreted in urine as MTP and 0.5% as TPA over a
3-day period. Approximately 11% of the 50-mg dose was converted to MTP and 0.6% was
converted to TPA. The parent compound was not found in the urine at either dose. A U.S. EPA
study (2004a) predicts rapid urinary excretion of TPA on the basis of its structure. As noted
earlier, however, only a minimal amount is predicted to be absorbed, at least in nonruminant
species.
Skinner and Stallard (1963) reported that, after the administration of a single oral dose
(100 or 1000 mg/kg) to dogs, 90% and 97% was eliminated unchanged in the feces at 24 hours
and 96 hours, respectively. Approximately 3% was converted to MTP; of this, 3%, 2% was
eliminated in the urine and 1% in the feces. MTP and TPA have also been identified in rat urine
(U.S. EPA, 2004a).
Dacthal Degradates — May, 2008 6-3
-------
Dacthal Degradates — May, 2008 6-4
-------
7.0 HAZARD IDENTIFICATION
7.1 Human Effects
7.1.1 Short-Term Studies and Case Reports
There are no studies of intentional or accidental ingestion of TPA or MTP in humans. A
single dose of 25 or 50 mg of DCPA, however, did not cause any observable effects in humans
(Tusing, 1963).
7.1.2 Long-Term and Epidemiological Studies
There are no long-term exposure or epidemiology studies of TPA or MTP exposure.
7.2 Animal Studies
7.2.1 Acute Toxicity
There are no acute toxicity studies on TPA or MTP after oral exposure in animals. The
50% lethal dose (LD50) for the parent compound DCPA is greater than 12,500 mg/kg in Spartan
rats (Wazeter et al., 1974a) and greater than 10,000 mg/kg in beagle dogs (Wazeter et al.,
1974b). These LD50 values are indicative of low acute toxicity for DCPA.
The dermal LD50 for DCPA in albino rabbits is greater than 10,000 mg/kg (Elsea, 1958).
A single application of 3.0 mg of dacthal to the eyes of albino rabbits produced a mild degree of
irritation that subsided completely within 24 hours after treatment (Elsea, 1958).
There are no acute toxicity studies on TPA or MTP via dermal or inhalation exposure.
7.2.2 Short-Term Studies
Hazleton Laboratories (1961) conducted a 28-day study of 0 or 1% TPA (860 mg/kg/day
based on U.S. EPA (1988) data on food intake and body weight) in the diet of male Sprague
Dawley rats (n= 10/group). Nasal discharge was noted in some control and exposed rats during
the study but did not appear to be treatment related. Clinical signs, body weights, liver and
kidney weights were measured and the tissues subjected to gross and histological examination.
No signs of toxicity were noted at the dose tested.
A 30-day intubation study using doses of 0, 100, 500, or 2000 mg of TPA per kg/day in 0.5%
methylcellulose solution was conducted in groups of 10 male and 10 female Sprague Dawley
rats (Major, 1985). There were no treatment-related mortalities or changes in organ weights
(adrenals, brain, gonads, heart, liver and kidney). Gross and histological evaluations of the
organs at the high dose and selected tissues at the lower doses did not reveal any abnormalities.
Soft stools (both sexes) as well as occult blood in the urine and increases in hemoglobin and
Dacthal Degradates — May, 2008 1-1
-------
hematocrit for males at the 2000 mg/kg/day dose, were originally identified as a non-adverse
LOEL (U.S. EPA, 1994c, 1998c) and the NOEL was 500 mg/kg/day.
The results from the short-term TPA study differed from those for DCPA in a 28-day
dietary study in groups of five male and female Sprague-Dawley rats given doses of 0, 250,
1000, or 2000 mg/kg/day (ISK Biotech Corp., 1990b). In the DCPA study, there was a dose-
related increase in liver weight and centrilobular hypertrophy of hepatocytes. The lowest dose
tested (250 mg/kg/day) was the LOAEL for these effects (U.S. EPA, 1994c). The difference in
the effect levels suggests that the parent DCPA is more acutely toxic than the TPA degradate.
The results of a 28-day study of MTP by Hazleton Laboratory (1961), comparable to
Hazleton's TPA study described above, did not identify any signs of toxicity at the 1% (860
mg/kg/day) dietary dose tested.
7.2.3 Subchronic Studies
A 90-day feeding study (Goldenthal et al., 1977) of TPA was performed in Charles River
CD rats (15/sex/dose), using doses of 0, 50, 500, 1000, or 10,000 ppm in the diet. These doses
were estimated to be equivalent to 0, 2.5, 25, 50, and 500 mg/kg/day, respectively. The control
and high dose animals were evaluated for clinical signs of toxicity: body weights, organ weights
and tissue histopathology. Blood and urine were evaluated at 1,2, and 3 months. There were no
adverse effects observed based on clinical observations of the high dose and control animals.
Therefore, the NOAEL was set at greater than or equal to the highest dose, 500 mg/kg/day, and
an LOAEL could not be determined.
Like those of short-term studies, the results of subchronic exposures of Sprague-Dawley
rats to DCPA differed from those for TPA. Groups of 15 male and 15 female animals were
given doses of 0, 10, 50, 100, 150, or 1000 mg/kg/day in their diets for 13 weeks (ISK Biotech
Corp., 1991). No clinical signs were observed and no effects on body weights were seen in the
males, although there was a dose-related trend toward lower weight gain in the females. Liver
weights and the incidence of centrilobular hepatocyte hypertrophy were increased in a dose-
related manner. Kidney weights were increased, and there was evidence of tubular regenerative
hyperplasia and follicular hypertrophy. The LOAEL was determined to be the 50-mg/kg/day
dose and the NOAEL the 10-mg/kg/day dose (U.S. EPA, 1994c).
The liver was also the target organ in a subchronic study of DCPA in CD-I mice
(Fermenta Plant Protection Co., 1988). The lowest effect levels were 1235 mg/kg/day for males
and 1049 mg/kg/day for females, based on minimal centrilobular hepatocyte enlargement. The
NOAELs in males and females were 406 and 517 mg/kg/day, respectively (U.S. EPA, 1994c).
No subchronic studies of MTP were identified.
Dacthal Degradates — May, 2008 7-2
-------
7.2.4 Neurotoxicity
No studies are available on the neurotoxicity of either TPA or MTP. Some dose-related
signs of nervous system effects (ataxia, decreased motor activity, poor righting reflex) were seen
in New Zealand White rabbits during a developmental study of DCPA after exposure to doses of
0, 500, 1000, or 1500 mg/kg/day during gd 6-19 (Fermenta Plant Production Co., 1989; U.S.
EPA, 1994c).
7.2.5 Developmental/Reproductive Toxicity
Pregnant rats (25 per dose group) were administered 0, 625, 1250, or 2500 mg of TPA
per kg/day via gavage on gd 6-15 (Mizen, 1985, U.S. EPA; 1998c). The dams were observed for
clinical signs, body weights, and food intake. After sacrifice, the ovaries were examined for
corpora lutea, and the uterus for implantations, early and late resorptions, live and dead pups.
Because no developmental effects were noted, the NOAEL for developmental effects was
identified as 2500 mg/kg/day. The LOAEL for developmental effects could not be determined.
Maternal toxicity, however, was noted at 2500 mg/kg/day, based on soft stools, red mucus in the
feces, salivation, decreased body weight gain, and decreased food consumption. A LOAEL of
2500 mg/kg/day and a NOAEL of 1250 mg/kg/day were set for the dams. There were no studies
of the developmental or reproductive toxicity of MTP.
Reproductive and developmental testing of DCPA has been evaluated in rats (Sprague-
Dawley) and rabbits (New Zealand White). The parent compound was minimally toxic. In the
two-generation study, the NOAEL for reproductive toxicity was 63 mg/kg/day and the LOAEL
was 319 mg/kg/day, based on decreased pup body weight (ISK Biotech Corp., 1990a). In the Fx
generation, there was an apparent increase in stillbirths at the highest dose level
(1273 mg/kg/day for the dams), which was more pronounced in the second generation than in the
first. Decreased body weight gain in the parents established the LOAELs for the parents at 319
mg/kg/day for the dams and 952 mg/kg/day for the males. The NOAELs for the dams and males
were 63 and 233 mg/kg/day, respectively (U.S. EPA, 1994c).
Developmental testing of CD rats exposed on gd 6-15 failed to identify an LOAEL; the
NOAEL was 2000 mg/kg/day (SDS Biotech Corp., 1986). Similar results were seen in New
Zealand White rabbits exposed to DCPA by gavage during gd 7-19. The NOAEL and highest
dose tested was 500 mg/kg/day (Fermenta Plant Protection Co., 1989). In a second study in New
Zealand White rabbits by the same company, there were some (four) maternal deaths at the
lowest dose of 500 mg/kg/day. Thirteen maternal deaths occurred at a dose of 1000 mg/kg/day
and 12 maternal deaths occurred at 1500 mg/kg/day. The animals that died had signs of
neurotoxicity, and the mid- and high-dose groups had a higher incidence of gastric ulcerations
than controls. No embryo or fetal toxicity or teratogenicity was observed (U.S. EPA, 1994c).
7.2.6 Chronic Toxicity
Long-term studies of DCPA have been conducted in dogs, rats, and mice. These studies
evaluated both cancer and noncancer endpoints. Hazleton and Dieterich (1963) fed beagle dogs
Dacthal Degradates — May, 2008 7-3
-------
(four per sex per dose) DCPA in the diet at 0, 100, 1000, or 10,000 ppm for 2 years. Based on
body weight and food consumption data provided in the report, these dietary levels are
approximately 0, 2.6, 17.7, or 199 mg/kg/day for males and 0, 3, 20.7, or 238 mg/kg/day for
females, respectively. Physical appearance, behavior, food consumption, hematology,
biochemistry, urinalysis, organ weight, organ-to-body weight ratio, gross pathology, and
histopathology were comparable in treated and control groups at all dose levels. An NOAEL of
10,000 ppm (199 mg/kg/day for males and 238 mg/kg/day for females), the highest dose tested,
was identified for this study.
Paynter and Kundzin (1963) fed albino rats (35 per sex per dose; 70 per sex for controls)
DCPA in the diet for 2 years at 0, 100, 1000, or 10,000 ppm. Based on food consumption and
body weight data provided in the report, these dietary levels correspond approximately to 0, 5,
50, or 500 mg/kg/day. Interim sacrifices were conducted at 13 and 52 weeks. Physical
appearance, behavior, hematology, biochemistry, organ weights, body weights, gross pathology,
and histopathology of treated and control animals were monitored. After 3 months at
10,000 ppm, slight hyperplasia of the thyroid was reported in both sexes. After 1 year, increased
hemosiderosis of the spleen occurred in females at 10,000 ppm, and there were slight alterations
in the centrilobular cells of the liver of both sexes. Kidney weights were increased significantly
in males fed 10,000 ppm, and adrenal weights were increased in females at the end of the 2-year
study. Based on these data, a NOAEL of 1000 ppm (50 mg/kg/day) and a LOAEL of 10,000
ppm (500 mg/kg/day) were identified.
A second 2-year feeding study of DCPA in rats was conducted by ISK Biotech
Corporation (1993). In this study, Sprague-Dawley rats (70 per sex per dose) were administered
technical-grade DCPA in their diets at doses of 0, 1, 10, 50, 500, or 1000 mg/kg/day. The
material used contained 0.13% hexachlorobenzene as an impurity. The animals were examined
for body weights and clinical signs. After sacrifice, the organs were examined for gross
pathology and tissue histopathology.
There was a dose-related increase in the incidence and severity of focal accumulation of
foamy-appearing macrophages within the alveolar spaces in males and females. Increases in
both the incidence and severity of centrilobular swelling (hepatocytic hypertrophy) were
observed at both interim and terminal sacrifices. Chronic nephropathy was increased in severity
in males and in incidence in females. Thyroid-stimulating hormone (TSH) was elevated at
52 weeks in a dose-related manner. It also was increased at 104 weeks, but the increase was not
dose-related. Thyroxin (T4) was decreased throughout the study, and triiodothyronine (T3) was
decreased at 52 weeks. The LOAEL for systemic toxicity was determined to be 10 mg/kg/day
on the basis of effects observed in the lungs, kidneys, thyroid, and thyroid hormone levels in
both sexes. The NOAEL was determined to be 1 mg/kg/day (ISK Biotech Corp., 1993). Tumors
of the thyroid and liver were also observed. The cancer findings from this study are discussed in
Section 7.2.7.
Groups of CD-I mice (90 per sex per dose) were administered dacthal in the diet for
2 years, using technical-grade DCPA (Fermenta Plant Protection Co., 1988). The dosage levels
were 0, 100, 1000, 3500, or 7500 ppm, equivalent in males to 0, 12, 123, 435, and 930
Dacthal Degradates — May, 2008 7-4
-------
mg/kg/day and in females to 0, 15, 150, 510, and 1141 mg/kg/day. The effects observed after
exposure to the test material included corneal opacities and increased relative liver weight (in
both sexes in the 7500-ppm group). Liver enzyme activities were increased, but not in a dose-
related manner, in both sexes at dietary concentrations of greater than 1000 ppm. There was also
a dose-related increase in cholesterol levels in females from the highest two dose groups and
hepatocyte enlargement/vacuolation in both sexes at 7500 ppm. Therefore, based on liver
effects, the LOAEL for systemic toxicity was identified as 7500 ppm (male, 930 mg/kg/day;
female, 1141 mg/kg/day). The NOAEL for systemic toxicity is 3500 ppm (male, 435
mg/kg/day; female, 510 mg/kg/day). A supplementary 2-year study in Sprague-Dawley rats
(Fermenta ASC Corp., 1990) to investigate the finding on corneal opacity in CD-I mice failed to
replicate this effect.
7.2.7 Carcinogenicity
There are no carcinogenicity studies for either TPA or MTP. The parent compound
(DCPA; doses of 0 to 1000 mg/kg/day) was shown to induce thyroid tumors in male and female
rats, liver tumors in female rats (ISK Biotech Corp., 1993), and liver tumors in female mice
(Fermenta Plant Protection Co., 1988; doses 0 to ~ 1000 mg/kg/day) in the chronic toxicity
studies discussed in Section 7.2.6. There was no significant increase in tumor incidence in the
Paynter and Kundzin (1963) study in albino rats with dietary doses of 0 to 500 mg/kg/day.
However, the ISK Biotech Corporation (1993) and Fermenta Plant Protection Company (1988)
studies used technical-grade DCPA containing impurities (0.13% hexachlorobenzene), whereas
the Paynter and Kundzin (1963) study used a purer grade of the chemical (Klopman et al., 1996).
In the ISK Biotech Corporation (1993) study, the incidence of liver combined adenoma,
carcinomas and hepatocholangiocarcinomas in female Sprague Dawley rats was 0%, 0%, 3%,
1%, 11%, and 16 % for doses of 0, 1, 10, 50, 500, and 1000 mg/kg/day, respectively. The first
adenoma appeared at week 53 and the first carcinoma at week 96; the numbers of adenomas was
greater than the number of adenomas. The thyroid tumors were observed in both males and
females. In males, neither the adenomas or adenomas and carcinomas combined demonstrated a
dose-response trend with incidences of 2%, 4%, 4%, 17%, 19%, 13%, respectively, for the
adenomas and 3%, 5%, 5%, 13%, 16%, 10%, respectively, for combined carcinomas and
adenomas (U.S. EPA, 1995b). In females the situation was similar with adenoma incidences of
2%, 2%, 4%, 7%, 2%, and 7%, respectively, and combined carcinoma and adenoma incidences
of 2%, 2%, 5%, 7%, 3%, 12%, respectively (U.S. EPA, 1995b).
Hepatocyte hypertrophy and thyroid follicular cell hyperplasia or hypertrophy occurred
in subchronic (28-day and 90-day) rat studies of DCPA, as well as in the long-term ISK Biotech
Corporation (1993) and Paynter and Kundzen (1963) studies. The short-term studies that have
been conducted for TPA have not provided any evidence for either thyroid or liver effects at the
doses tested, reducing concern that TPA might have tumorigenic properties (U.S. EPA, 2004a).
No short- or long-term toxicity data are available for MTP.
Male and female CD-I mice both developed carcinomas and adenomas in the liver
(Fermenta Plant Protection Company, 1988). Tumors were found in the controls as well as the
Dacthal Degradates — May, 2008 7-5
-------
exposed animals. The tumors in male mice fell withing the range for historical controls from 9
studies in CD-I mice (27-56% for adenomas and carcinomas combined; 4-27% for adenomas
alone; U.S. EPA, 1995a). The incidence of adenomas the female mice at the high dose (11%)
was slightly greater than that for the historic controls (2-8%). The same was true for combined
adenomas and carcinomas (12%) when compared to the historic controls (4-10%). There was
also a dose-response trend for the numbers of adenomas with incidences of 3%, 0%, 3%, 5%,
and 11% for the 1, 100, 1000, 3500, and 7500 mg/kg/day doses, respectively (U. S. EPA,
1995b).
7.3 Other Key Data
7.3.1 Mutagenicity and Genotoxicity
TPA did not induce a mutagenic response in either the Ames (Godek 1984) or
hypoxanthine guanine phosphoribosyl transferase assays with or without metabolic activation
(Godek, 1985). TPA also did not induce a significant increase in the frequency of sister
chromatid exchange in Chinese hamster ovary cells with or without metabolic activation (San
Sebastian, 1985).
TPA has not been found to induce an increase in unscheduled DNA synthesis
(Barfknecht, 1984). An in vivo mouse micronucleus assay (7/sex/group) with TPA was negative
in females and equivocal in males (a weak response at the highest dose) in a study by Siou
(1985). The males were given doses of 0, 1000, 5000, or 10000 mg/kg by gavage and the
females 0, 500, 2500, or 5000 mg/kg, both in methylcellulose. High doses were used in most of
the genotoxicity assays; limitations on solubility may have influenced the results.
DCPA had no mutagenic activity, with or without activation, in Salmonella assays
(Auletta et al., 1977), in in vivo cytogenetic tests (Kouri et al., 1977a), in DNA repair tests
(Auletta and Kuzava, 1977), or in dominant lethal tests (Kouri et al., 1977b).
7.3.2 Immunotoxicity
No studies are available on the immunotoxicity of DCPA, TPA, or MTP.
7.3.3 Hormonal Disruption
No studies are available on the ability of TPA or MTP to influence hormone production
or activity. However, DCPA caused histopathological changes in the thyroid, along with
decreased levels of T4 and T3, in Sprague-Dawley rats at doses greater than or equal to 10
mg/kg/day. TSH levels were elevated at 50 and 104 weeks. The subchronic study of TPA did
not reveal any histopathological changes in the thyroid at a dose of 500 mg/kg/day. There was
no evaluation of thyroid hormones in the TPA study.
Dacthal Degradates — May, 2008 7-6
-------
7.3.4 Structure-Activity Relationship
Klopman et al. (1996) evaluated the carcinogenic potential of DCPA and TPA on the
basis of their chemical and biological properties and the multiple computer automated structure
evaluation (MULTICASE) artificial intelligence program (a QSAR model). The MULTICASE
system training set for mutagenicity and cytotoxicity included all the Ames assay results from
the National Toxicology Program (NTP). The cancer projections were trained with the NTP
bioassay results as well as a carcinogen potency database by Gold et al. (1984, 1986, 1987, 1990,
1993). The QSAR program produced consistently negative findings for DCPA and TPA, leading
to the conclusion that neither molecule was predicted to be carcinogenic or mutagenic.
The prediction for lack of carcinogenicity for DCPA was somewhat unexpected, because
it had been found to have a weak tumorigenic response in rats (ISK Biotech Corp., 1993) and
mice (Fermenta Plant Protection Co., 1988). In trying to develop a rationale for the positive
response of dacthal in the study by ISK Biotech Corporation, Klopman et al. (1996) noted that
the negative Paynter and Kundzin (1963) bioassay of DCPA in rats was conducted with pure
dimethyl-tetrachloroterephthalate, whereas the later, weakly positive studies used technical-
grade material. For that reason, Klopman et al. (1996) obtained a list of the impurities in
technical-grade DCPA and evaluated those materials with the MULTICASE program. Although
the authors did not present a list of the impurities they tested, they did report that most of them
resulted in a positive carcinogenicity finding by the MULTICASE program.
Hexachlorobenzene, the best-documented and most frequently mentioned impurity, was found to
be carcinogenic in a bioassay conducted by NTP.
Klopman et al. (1996) also examined the alkylating properties of TPA in relation to those
of DCPA, as reflected in the ability of these compounds to react with y-4-nitrobenzylpyridine
(y4-NBP). Dacthal demonstrated some ability to react with y4-NBP, whereas TPA did not
react. The y4-NBP reactivity opens the possibility that DCPA's alkylating potential, alone or in
combination with the carcinogenicity of the product impurities, might explain the weak
tumorigenic response in the ISK Biotech Corporation (1993) study. This study supports the
conclusion that TPA is unlikely to be tumorigenic.
7.4 Hazard Characterization
7.4.1 Synthesis and Evaluation of Major Noncancer Effects
The only noncancer health effects noted with TPA were soft stools and occult blood in
urine at doses of greater than 2000 mg/kg/day (Major, 1985). Doses of 2500 mg/kg/day
administered during gd 6-15 also caused soft stools, increased salivation, decreased body weight
gain, and decreased food consumption (Mizen, 1985). No effects were observed in the single
study of MTP (Hazelton, 1961).
The data available from chronic and subchronic studies of DCPA demonstrate that it can
affect multiple organ systems (lungs, liver, thyroid) in rats and liver in mice. The LOAEL for
the noncancer critical effects in rats is 10 mg/kg/day, whereas that in mice is approximately 100-
Dacthal Degradates — May, 2008 7-7
-------
fold higher (1000 mg/kg/day). No adverse health effects were observed in dogs at doses of
about 200 mg/kg/day (Diamond Alkali Co. 1963; U.S. EPA, 1994c).
The data from chronic and subchronic studies of dacthal in rats and mice identify the rat
as the most sensitive laboratory species. A comparison of the subchronic effect level from rats
for DCPA (10 mg/kg/day) with the NOAEL for TPA (>500 mg/kg/day) supports the conclusion
that TPA is at least an order of magnitude less toxic than its parent chemical.
7.4.2 Synthesis and Evaluation of Carcinogenic Effects
There are no carcinogenicity studies of either TPA or MTP. There is some evidence for
the carcinogenic potential of the parent compound DCPA, based on the induction of thyroid and
liver tumors in rats and of liver tumors in mice. The U.S. EPA (1998c) concluded that the
evidence for the carcinogenicity of DCPA may reflect, at least in part, the carcinogenicity of
several of the impurities in the test material.
In DCPA subchronic rat studies, thyroid and liver tumors were preceded by tissue lesions
and hepatocyte hypertrophy, which occurred at a dose of greater than 215 mg/kg/day (the lowest
dose tested) in a 28-day feeding study and a dose of 100 mg/kg/day in a 90-day feeding study.
Thyroid follicular cell hyperplasia or hypertrophy occurred at a dose of 1720 mg/kg/day in a
28-day feeding study and at a dose of 1000 mg/kg/day in a 90-day feeding study (U.S. EPA,
2004a).
No liver or thyroid precursor events occurred in rats after a subchronic feeding study
with up to 500-mg/kg/day doses of TPA. In addition, TPA has not been demonstrated to be
mutagenic. The U.S. EPA (2004a, 2004b) concluded that TPA is unlikely to pose a cancer risk.
As described in Section 7.3.4, Klopman et al. (1996) reached the same conclusion regarding the
carcinogenic potential of TPA, using QSAR analysis combined with an evaluation of its
chemical properties.
7.4.3 Mode of Action and Implications in Cancer Assessment
There are no cancer data for either MTP or TPA. The mode of action proposed for the
tumors observed in the chronic studies of DCPA relates primarily to the presence of potentially
carcinogenic impurities (polyhalogenated dibenzo-p-dioxins, dibenzofurans, and
hexachlorobenzene) in the material tested. Early commercial preparations of DCPA could
contain up to 0.3% hexachlorobenzene as an impurity. Dioxin/furanes also were present at
times. Hexachlorobenzene is a probable human carcinogen and, like DCPA, is associated with
liver, kidney, and thyroid tumors in laboratory animals (U.S. EPA, 1988c).
Although it is hypothesized that impurities contributed to the carcinogenic activity of
DCPA, at the concentrations present, they cannot account for all of the DCPA cancer risk (U.S.
EPA, 1998). It is possible that weak alkylation activity associated with the methyl ester
conformation of DCPA and/or nongenotoxic mechanisms may also be involved in the tumor
response (Klopman et al., 1996).
Dacthal Degradates — May, 2008
-------
7.4.4 Weight-of-Evidence Evaluation for Carcinogenicity
Although there is little weight-of-evidence information available, the lack of precursor
effects compatible with the DCPA data and QSAR projections supports the conclusion that TPA
is probably not carcinogenic. Not enough data are available to perform a weight-of-evidence
assessment on MTP.
There is suggestive evidence of the carcinogenic potential of the parent compound
DCPA, based on the induction of thyroid and liver tumors in rats and liver tumors in mice (U.S.
EPA, 1998c).
7.4.5 Potentially Sensitive Populations
No sensitive populations have been identified. Results of a single developmental study
indicate that exposure of pregnant dams to doses of <2500 mg/kg/day via gavage on gd 6-15 did
not cause a toxic effect to the fetuses.
Dacthal Degradates — May, 2008 7-9
-------
Dacthal Degradates — May, 2008 7-10
-------
8.0 DOSE-RESPONSE ASSESSMENT
8.1 Dose-Response for Noncancer Effects
An RfD has not been set for either MTP or TPA because of the incompleteness of the
database on these compounds. The U.S. EPA (1998c), however, suggests that the RfD for the
parent compound, DCPA, is sufficient to protect against any toxicity from its metabolites. 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 data needed to derive a reference concentration (RfC) for MTP, TPA, or DCPA are
not available. The RfC is an estimate of the daily inhalation exposure to the human population
that is likely to be without appreciable risk of deleterious effects over a lifetime.
8.1.1 RfD Determination
Choice of Principal Study and Critical Effect
A chronic 2-year feed study of DCPA (containing 0.13% of the impurity
hexachlorobenzene) in Sprague-Dawley rats (70 per sex per dose) was used as the basis for
determining the RfD (U.S. EPA, 1994c, 1998c). There was a dose-related increase in the
incidence and severity of focal accumulation of foamy-appearing macrophages within the
alveolar spaces in the lungs of both males and females. Increases in both the incidence and
severity of centrilobular swelling (hepatocytic hypertrophy) were observed at both interim and
terminal sacrifices. Chronic nephropathy was increased in severity in males and in incidence in
females. TSH was elevated at 52 weeks in a dose-related manner. TSH also was increased at
104 weeks, but the increase was not dose related. T4 was decreased throughout the study, and T3
was decreased at 52 weeks. The LOAEL for systemic toxicity was 10 mg/kg/day, based on
effects observed in the lungs, kidneys, thyroid, and thyroid hormones of both sexes. The
NOAEL was determined to be 1 mg/kg/day (ISK Biotech Corp., 1993). This was chosen as a
critical study for establishing the HRL for TPA and MTP in the absence of adequate studies on
either DCPA degradate.
Dose-Response Characterization
As described above, the chronic 2-year feed study of DCPA (with the hexachlorobenzene
impurity) in Sprague-Dawley rats is the critical study used in developing an RfD for DCPA, the
parent compound for TPA and MTP, using the NOAEL/LOAEL approach as follows:
RfD = 1 mg/kg/dav = 0.01 mg/kg/day
100
where:
1 mg/kg/day = The NOAEL from a chronic study of DCPA in rats in which a variety of
adverse effects were observed at an LOAEL of 10 mg/kg/day
Dacthal Degradates — May, 2008 8-1
-------
100 = An uncertainty factor that includes a 10 to adjust for intraspecies variability and a
10 for interspecies variability
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, use of NOAEL or LOAEL, or duration adjustment.
The RfD for DCPA is lower than the chronic level of concern of 0.05 mg/kg/day
established by the EPA Office of Pesticide Programs (U.S. EPA, 2004b) for TPA. This
determination is based on the NOAEL from the subchronic TPA study, using a total uncertainty
factor of 1000 (10 for interspecies extrapolation, 10 for intraspecies variability, and 10 to adjust
for the subchronic exposure duration). Accordingly, the use of the DCPA RfD to establish the
HRL for regulatory determination for MTP and TAP is a health-risk-protective measure.
8.1.2 RfC Determination
There are insufficient data to determine an RfC for DCPA, MTP, or TPA.
8.2 Dose-Response for Cancer Effects
No data are available for cancer effects from TPA or MTP. DCPA has been
demonstrated to cause liver and thyroid tumors in rats and liver tumors in mice. However, no
liver or thyroid precursor events occurred in studies of TPA with dosing regimens of 2000
mg/kg/day for 30 days or 500 mg/kg/day for 90 days. This suggests that TPA is lexicologically
different from DCPA. In addition, TPA has not been demonstrated to be mutagenic.
Accordingly, the U.S. EPA (2004a) concluded that TPA is unlikely to pose a cancer risk.
Klopman et al. (1996) demonstrated that TPA did not act as an alkylating agent in a chemical
test system, and the results of QSAR analysis with the MULTICASE program supported the
EPA's conclusion concerning the cancer risk of TPA. Lack of toxicity data for MTP, prevents a
quantitative or qualitative assessment of its potential carcinogenicity.
A quantitative cancer assessment was conducted for dacthal by OPP (U.S. EPA., 1995b).
Liver and thyroid tumors were observed in male and female Sprague Dawley rats (ISK Biotech
Corp., 1993) using doses of 0-1000 mg/kg/day. No tumors were observed in Albino rats
exposed to doses of 0 to 500 mg/kg/day (Paynter and Kundzin, 1963). The dose range achieve
in the Paynter and Kundzin (1963) study was lower than that for the ISK Biotech Corporation
(1993) study, and it also reportedly used a purer form of DCPA. Other than the tumors, the
high-dose histological effects on the thyroid and liver were similar in both studies: thyroid
hyperplasia and histological changes in the centrilobular cells of the liver.
In CD-I mice there was an increase primarily of adenoma's of the livers of the males and
females compared to controls. In males, the incidence did not exhibit a dose-response trend and
Dacthal Degradates — May, 2008 8-2
-------
fell within the historic control range, while in females there was a weak dose-response with the
incidence at the high dose slightly greater than that for the historic controls for adenomas (U.S.
EPA, 1995b).
8.2.1 Choice of Study
The U.S, EPA (1995b) selected the liver tumors in the female rats from the ISK Biotech
Corporation (1993) study as the basis for quantification of the carcinogenic potential of DCPA.
Although it was concluded that the impurities in the tested material could, in part, account for
the tumors observed, they could not unequivocally account for the total tumor response. DCPA
was classified as a Group C (Possible) carcinogen under the Agency 1986 cancer guidelines..
8.2.2 Dose-Response Characterization
The dose-response data for the liver tumors in female Sprague Dawley rats are
summarized in Table 8-1. Although, DCPA was evaluated against the U.S. EPA 1986 Guidelines
for Carcinogen Risk Assessment, a body weight374 conversion was used for the DCPA analysis
rather than the then conventional body weight273 (U.S. EPA, 1998). The body weight scaling
factor is consistent with that used in the Agency 2005 cancer guidelines. Dose-response was
modeled using the linear multistage model.
Table 8-1 Hepatocellular Tumors in Female Sprague-Dawley Rats
Tumor/Dose (mg/kg/day)
Adenomas
Carcinomas
Hepatocholangeocarcinomas
Combined
0
0/69
0/69
0/69
0/69
1
0/69
0/69
0/69
0/69
10
1/67
1/67
0/67
2/67
50
1/68
0/68
0/68
1/68
500
5/70
3/70
0/70
8/70
1000
7/68
3/68
2/68
11/68
Source: U.S. EPA (1995b)
8.2.3 Cancer Potency and Unit Risk
The calculated slope factor for DCPA is 1.49 x 10'3 (mg/kg/day)"1 (U.S. EPA, 1998); the
10-6 risk concentration in water is 23 |-ig/L. There is uncertainty in these values because of the
carcinogenicity of some of the impurities present in the material tested. The cancer assessment
for the parent compound can be applied to its MTP and TPA degradates in the absence of
tumorgenicity data on either material. However to do so for TPA would be conservative given
the lack of precursor effects in the TPA subchronic study.
Dacthal Degradates — May, 2008
8-3
-------
Dacthal Degradates — May, 2008 8-4
-------
9.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK
FROM DRINKING WATER
9.1 Regulatory Determination for Chemicals on the Contaminant Candidate List
The SDWA, as amended in 1996, required the 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
eight 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 41 chemicals and 10 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, 2004c).
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 9.1.1. 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.
9.1.1 Criteria for Regulatory Determination
Following are the three criteria used to determine whether 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 and promulgation of a National Primary Drinking Water Regulation
(NPDWR) for that contaminant. The Agency may determine that there is no need for a
Dacthal Degradates — May, 2008 9-1
-------
regulation when a contaminant fails to meet one of the criteria. A decision not to regulate is
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.
9.1.2 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 NDWAC 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
NDWAC 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 semiquantitative
tool for addressing each of the three CCL criteria. The NDWAC requested that the EPA use
good judgment in balancing the many factors that need to be considered in making a regulatory
determination.
The EPA modified the semiquantitative NDWAC suggestions for evaluating chemicals
against the regulatory determination criteria and applied them in decision-making. The
quantitative and qualitative factors for dacthal degradates (TPA and MTP) that were considered
for each of the three criteria are presented in the sections that follow.
9.2 Health Effects
The first criterion asks whether the contaminant may have an adverse effect on the health
of persons. Because all 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 to estimate a dose at
which adverse health effects are either not likely to occur (threshold toxicant) or to have a low
probability for occurrence (nonthreshold 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 RfD for threshold effects, and the slope factor for nonthreshold effects.
A full description of the health effects associated with exposure to TPA and MTP is
presented in Chapter 7 of this document and summarized below in Section 9.2.2. Chapter 8 and
Section 9.2.3 present dose-response information.
Dacthal Degradates — May, 2008 9-2
-------
9.2.1 Health Criterion Conclusion
The limited toxicological data on the health effects of the dacthal degradates MTP and
TPA led to a two-level evaluation of these compounds for their heath effects. Following the
recommendation of the EPA's Office of Pesticide Programs, both derivatives were first
evaluated in terms of the health effects caused by the parent material (DCPA). Since the TPA
degradate has been studied for its toxicological properties, it was also evaluated independently.
Because of a lack of data, the effects of the MTP degradate could be determined only in terms of
the toxicity of the parent compound. However, intestinal conversion of much of DCPA to MTP
for absorption provides justification for this approach.
Both DCPA and TPA cause adverse health effects in laboratory animals. However, the
effects associated with TPA are much milder than those of the parent and tend to occur at doses
that are lower by about an order of magnitude. TPA is weakly toxic, causing effects on weight
gain and stool consistency at its lowest effect levels. DCPA can cause a variety of systemic
effects on liver, kidney, thyroid, and, potentially, the eyes. It may also have some tumor-
initiating or tumor-promoting properties.
9.2.2 Hazard Characterization and Mode of Action Implications
Currently, no subchronic or chronic studies are available to assess the toxicological
effects of MTP (the mono-acid degradate). Three studies in rats (30- and 90-day feeding studies
and a developmental study) are available for TPA (the di-acid degradate). The effects of
exposure were mild (weight loss and diarrhea) and occurred at doses greater than or equal to
2000 mg/kg/day. No reproductive effects were observed at a maximum dose of 2,500
mg/kg/day. The critical effects for DCPA, the parent compound, include effects on the lung,
liver, kidney, and thyroid in male and female rats in a 2-year chronic bioassay (ISK Biotech
Corp., 1993).
No carcinogenicity studies have been performed with either TPA or MTP. Based on a
comparison of TPA toxicity with that of its parent, and TPA's lack of mutagenicity, the EPA
(U.S. EPA, 2004b) concluded that TPA is unlikely to pose a cancer risk. Klopman et al. (1996)
evaluated the carcinogenic potential of TPA on the basis of its chemical and biological
properties and, using a variety of QSAR tools, determined that it did not present any substantial
carcinogenic risk.
There is suggestive evidence, based on an increased incidence of liver and thyroid tumors
in rats and liver tumors in mice, that DCPA could be carcinogenic. The presence of
hexachlorobenzene and dioxin as impurities could have contributed to the cancer risk. However,
it is also possible that dacthal itself could have some tumorigenic activity.
The EPA evaluated whether health information is available regarding the potential effects
of the dacthal degradates on children and other sensitive populations. There are no data that
identify a particular sensitive population for the degradates or the parent compound exposure.
Results of a single developmental study indicate that exposure to pregnant dams to doses of
Dacthal Degradates — May, 2008 9-3
-------
<2500 mg of TPA per kg/day via gavage did not have an adverse effect on the fetus. The EPA
did not identify any data that suggest gender-related differences in toxicity or sensitivity in the
elderly.
9.2.3 Dose-Response Characterization and Implications in Risk Assessment
The present toxicity database for MTP and TPA is not sufficient to derive RfDs for these
two chemicals. However, because the available data indicate that neither MTP nor TPA is more
toxic than its parent compound, DCPA, the Agency suggests that the RfD for the DCPA parent
would be protective against exposure from these two DCPA metabolites (U.S. EPA, 1998c).
Both compounds are formed in the body from the DCPA parent, and therefore the toxicity of the
degradates is reflected in the toxicity of the parent compound. The RfD for DCPA is 0.01
mg/kg/day, based on a chronic rat study (ISK Biotech Corp., 1993), with an NOAEL of 1.0
mg/kg/day and an uncertainty factor of 100 for interspecies and intraspecies variability.
The EPA derived the HRL for TPA and MTP using the DCPA RfD of 0.01 mg/kg/day
(U.S. EPA, 1994c) and a 20% relative source contribution. The Agency calculated an HRL of
0.07 mg/L or 70 |ig/L for DCPA and used this HRL for TPA and MTP.
9.3 Occurrence in Public Water Systems
The second criterion asks whether the contaminant is known to occur or whether there is
a substantial likelihood that the contaminant will occur in PWSs with a frequency and at levels
of public health concern. To address this question, EPA considered the following information:
• Monitoring data from PWSs
• Ambient water concentrations and releases to the environment
• Environmental fate
Data on the occurrence of the dacthal degradates TPA and MTP 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 TPA and MTP, as well those that reported
concentrations of TPA and MTP above an estimated drinking water HRL. For noncarcinogens,
the estimated HRL level was calculated from the RfD, assuming that 20% of the total exposure
would come from drinking water. For carcinogens, the HRL was the 10~6 risk level (i.e., the
probability of one excess tumor in a population of 1 million people). The HRLs are benchmark
values that were used in evaluating the occurrence data while the risk assessments for the
contaminants were being developed. The HRL for TPA and MTP is 70 |ig/L. The combined
concentrations of MTP and TPA were converted to their DCPA equivalents for the occurrence
analysis.
Dacthal Degradates — May, 2008 9-4
-------
The available monitoring data, including indications of whether the contaminant is a
national or 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.
9.3.1 Occurrence Criterion Conclusion
TPA and MTP are degradates of DCPA and are present only in areas where DCPA has
been used. DCPA and its derivatives have been detected in surface and ground water as well as
in PWSs. States reporting detections of the dacthal degradates are located across the country,
from east to west and north to south. TPA and MTP combined have not been detected at the
health reference level (HRL) in any large systems. They were found at levels exceeding the
HRL in 0.13% of small systems, affecting 0.02% of the population served by small systems,
approximately equivalent to 113,000 individuals nationwide. The one HRL exceedance
occurred in one small system in Michigan. Dacthal, MTP, and TPA have also been detected in
ambient waters in USGS surveys. However, in all cases, concentrations have been below the
HRL and ^HRL. Accordingly, TPA and MTP are likely to occur in PWSs but not at
concentrations of concern.
9.3.2 Monitoring Data
Drinking Water
Analytical methods for TPA and MTP cannot distinguish between the two compounds.
Accordingly, the results from the UCMR 1 program report both compounds as one. The first
cycle extended from 2001 to 2006. The MRL of the degradates was > 1 |ig/L. Results were
provided for small systems and large systems separately. A total of 797 small PWSs (590
ground water and 207 surface water) were tested, and 3272 samples were obtained. Among the
small systems, DCPA degradate detections (>MRL or > 1 |ig/L) were reported in 2.13%. A
single small system had a concentration greater than the HRL (>HRL or >70 |ig/L). This ground
water system represented 0.13% of small PWSs. A total of 3079 large PWSs (1389 ground
water and 1690 surface water systems) were tested, and 30,638 samples were obtained. Among
the large systems that reported results, 5.20% had detections (>MRL or > 1 |ig/L). A single
large surface water system had a concentration >/^HRL. No large system had detections of
concentrations >HRL (>70 |ig/L).
Ambient Water
Occurrence data for dacthal and MTP were collected by the NAWQA program from
1992 to 2001 (Cycle 1) in representative watersheds and aquifers across the country. Reporting
limits varied over the course of the cycle owing to improved methods of detection, but the level
of detection did not exceed 0.070 jig/L for dacthal and MTP. The MTP degradate was not
detected in ambient surface or ground water in mixed, undeveloped, or urban areas. In
agricultural areas, 1233 samples from 48 ambient surface water sites were tested at a detection
frequency of 0.18%. The maximum concentration was 0.430 |ig/L; both the median and the 95th
percentile concentrations were below the reporting limit. Ambient ground water samples in
agricultural areas were obtained from 1217 wells. The detection frequency was 0.08%; the
maximum concentration was 1.1 |ig/L, and both the median and 95th percentile concentrations
Dacthal Degradates — May, 2008 9-5
-------
were below the reporting limit. The parent DCPA was detected in both ambient and ground
water samples. The 95% concentrations for agricultural, mixed, and urban samples from
ambient surface waters were below the HRL and 1A HRL. Levels were below the reporting limit
for all ground water samples and from ambient surface waters sampled from undeveloped areas.
9.3.3 Use and Fate Data
DCPA is used as a selective, pre-emergence herbicide to control annual grasses and
broad-leaved weeds in turf. It is also applied to ornamentals, strawberries, certain vegetables,
nuts, and cotton (U.S. EPA, 1998c). Some use of DCPA on some vegetable and nut products
was terminated in 2005 along with residential turf and ornamental plant use. Today, 66
registered products contain dacthal as an active ingredient as well as 2 manufactured products,
Dacthal 1.92F and 90% dimethyl-T, from which all other products are formulated. Agricultural
use of DCPA is mainly on the east and west coasts and along the southern United States. TPA
and MTP are likely to occur in these areas. Approximately 80% of DCPA is used for weed
control on turf (e.g., golf courses) and home lawns, for which adequate estimations of use are not
available. There is no commercial use for TPA or MTP. However, DCPA photodegrades on soil
surfaces; after 5 hours of exposure to sunlight, 50% of this compound was degraded to MTP and
TPA (Chen et al., 1976).
Both TPA and MTP were determined to be highly mobile in all soils (U.S. EPA, 1998c).
MTP and TPA are expected to be more water soluble than the parent compound, based on
hydrolysis of the ester bonds and resultant increased hydrophilicity of the products. Thus, it is
expected that they will be more mobile in the soil. Limited physical or chemical data, however,
are available for these compounds. Data suggest that TPA will leach to ground water wherever
DCPA is used, regardless of soil properties (U.S. EPA, 1998c). TPA appears to be substantially
more persistent than the parent compound (DCPA) and exhibits low soil/water partitioning.
Therefore, substantial quantities of TPA should be available for runoff for a longer period than
the parent DCPA.
9.4 Risk Reduction
The third criterion asks whether, in the sole judgment of the administrator, regulation
presents a meaningful opportunity for health risk reduction for persons served by PWSs. 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 9.4.2 below.
To evaluate risk from exposure through drinking water, EPA considered the net
environmental exposure in comparison to the 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
Dacthal Degradates — May, 2008 9-6
-------
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 9.4.3 below.
In making its regulatory determination, EPA also evaluated effects on potentially
sensitive populations, including fetuses, infants, and children. Sensitive population
considerations are included in section 9.4.4.
9.4.1 Risk Criterion Conclusion
An estimated 113,000 individuals were served by systems with detections greater than
the HRL (all served from small systems); an additional 738,337 individuals, all served by large
systems, were exposed at levels >/^HRL. Although additional monitoring data are needed, food
and drinking water appear to be the major sources of exposure to DCPA. The impact of
regulating TPA and MTP concentrations in drinking water on health risk reduction is likely to be
small, based on limited occurrence at levels of potential toxicological concern. Thus, the
evaluation of the third criterion is negative.
9.4.2 Exposed Population Estimates
A total of 11,269,436 people were served by large PWSs in which TPA and MTP was
greater than the MRL (> 1 |ig/L). An estimated 1,118,000 people from small systems received
water with mono- and di-acid concentrations greater than the MRL. These values are a function
of the widespread use of DCPA, an herbicide, and the mobility of it and its degradates in the
environment. The number of individuals exposed to concentrations greater than either the HRL
or V2 the HRL was considerably smaller. An estimated 113,000 individuals served by small
PWSs were exposed to levels greater than the HRL. In large systems, there were no exposures
greater than the HRL, and 738,337 individuals were exposed to concentrations >!/2HRL from a
single large system.
9.4.3 Relative Source Contribution
Relative source contribution (RSC) analysis compares the magnitude of exposure
expected via drinking water to the magnitude of exposure from intake of TPA and MTP in other
media, such as food, air, and soil. Lack of recent monitoring data for air, foods, and soils would
preclude using a data-derived RSC value other than a default 20% at this time if a lifetime health
advisory were to be developed for noncancer effects.
9.4.4 Sensitive Populations
No sensitive populations have been identified. The limited data available on TPA
indicates that the rat fetus is not affected by oral exposure at levels below those that affect the
dams. There are also no data to suggest gender-related differences in the toxicity of TPA or
MTP.
Dacthal Degradates — May, 2008 9-7
-------
9.5 Regulatory Determination Decision
As stated in Section 9.1.1, a positive finding for all three criteria is required in order to
make a determination to regulate a contaminant. There are inadequate data to meet the
regulatory determination criteria for TPA or MTP. Based on the monitoring of ambient water
samples collected between 1992 and 2001 and of samples from PWSs collected between 2001
and 2006, TPA and MTP (combined) were detected in <5% of the systems tested, and
approximately 113,000 individuals were exposed to a level greater than or equal to the HRL.
Accordingly, it appears that TPA and MTP do not occur in PWSs with a frequency and at a level
constituting a public health concern at the present time. Therefore, regulation of TPA and MTP
does not present a meaningful opportunity for health risk reduction for persons served by PWSs.
Dacthal Degradates — May, 2008 9-8
-------
10.0 REFERENCES
Auletta, A. and J. Kuzava. 1977. Activity of DTX-77-0005 in a test for differential inhibition of
repair deficient and repair competent strains of Salmonella typhimurium [unpublished study].
Microbiological Associates Rpt. DS-0001. MRID 00100776 (as cited in U.S. EPA, 1988b).
Auletta, A., A. Parmar, and J. Kuzava. 1977. Activity of DTX-0003 in the
Salmonella/microsomal assay for bacterial mutagenicity [unpublished study]. Microbiological
Associates Rpt. DS-0002. MRID 00100774 (as cited in U.S. EPA, 1988b).
Barfknecht, TR. 1984. DNA repair test in rat hepatocyte primary cultures with
tetrachloroterephthalic acid. Pharmakon Research international Doc. No. 666-5TX-84-0042-002
(as cited in Michigan Department of Community Health, 2003).
Carey, A.E., J.A. Gowen, H. Tai, et al. 1979. Pesticide residue levels in soils and crops from 37
states, 1972 - National Soils Monitoring Program (IV). Pestic. Monit. J. 12:209-229 (as cited in
HSDB, 2004).
ChemFinder. 2004. Cambridge Soft Corporation, Cambridge, MA. Available from:
.
Chen, Y.L., et al. 1976. Chung-Kuo Nung Yeh Hua Hsueh Hui Chih 14:59-67 (as cited in
HSDB, 2004).
Choi, J.S., T.W. Fermanian, DJ. Wehner, et al. 1988. Effect of temperature, moisture, and soil
texture on DCPA degradation. Agron. J. 80:108-113 (as cited in HSDB, 2004).
DeVault, D.S. 1985. Contaminants in fish from Great Lakes harbors and tributary mouths. Arch.
Environ. Contain. Toxicol. 14(5):587-594 (as cited in HSDB, 2004).
DeVault, D.S., J.M. Clark, and G. Lahvis. 1988. Contaminants and trends in fall run coho
salmon. J. Great Lakes Res. 14:23-33 (as cited in HSDB, 2004).
Diamond Alkali Company. 1963. MRID No. 00083584. HED doc. No. 003299, 005866.
Available from EPA. Write to FOI, EPA, Washington DC 20460. (as cited in U.S. EPA, 1994c)
Elsea, J.R. 1958. Acute oral administration; acute dermal application; acute eye application
[unpublished study]. MRID 00045823 (as cited in U.S. EPA, 1988b).
FDA. (Food and Drug Administration). 2003. Food and Drug Administration total diet Study:
Summary of Residues found Ordered by Pesticide (Market Baskets 91-3 - 01-4. June.
http://www.cfsan.fda.gov/~acrobat/tdslbyps.pdf
Fermenta Plant Protection Company. 1988. MRID 40958701. HED Doc. No. 007250, 008095.
Available from EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
Dacthal Degradates — May, 2008 10-1
-------
Fermenta ASC Corporation. 1989. MRID 41054820. HED Doc. No. 0088229, 008409 Available
from EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
Fermenta ASC Corporation. 1990. MRID 41349101, 41750102. HED Doc. No. 008373.
Available from EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
Fleck, I.E., et al. 1988. Endosulfan and Chlorothal-dimethyl residues in soil and sediment of
Monterey County. (Environ Hazards Assess Program, California Dep Food Agric, Sacramento,
CA USA). Report 1988, EH-88-6; Order No. PB90-182635. pp. 47 (as cited in HSDB, 2004).
Frear, D.S. 1976. In: Kearney, P.C., and D.D. Kaufman (eds.). Herbicides: Chemistry
Degradation and Mode Action, 2nd ed. 2:541-607 (as cited in HSDB, 2004).
Gartrell, M.J., J.C. Craun, D.S. Podrebarac, et al. 1985a. Pesticides, selected elements, and other
chemicals in adult total diet samples, October 1978-September 1979. J. Assoc. Off. Anal. Chem.
68:862-875 (as cited in HSDB, 2004).
Gartrell, M.J., J.C. Craun, D.S. Podrebarac, et al. 1985b. Pesticides, selected elements, and other
chemicals in adult total diet samples, October 1979-September 1980. J. Assoc. Off. Anal. Chem.
68:1184-1197 (as cited in HSDB, 2004).
Gartrell, M.J., J.C. Craun, D.S. Podrebarac, et al. 1986a. Chemical contaminants monitoring.
Pesticides, selected elements, and other chemicals in infant and toddler total diet samples,
October 1980-March 1982. J. Assoc. Off. Anal. Chem. 69:123-145 (as cited in HSDB, 2004).
Gartrell, M.J., J.C. Craun, D.S. Podrebarac, et al. 1986b. Pesticides, selected elements, and other
chemicals in adult total diet samples, October 1980-March 1982. J. Assoc. Off. Anal. Chem. 69:
146-161 (as cited in HSDB, 2004).
Gershon, H., and G.W. McClure, Jr. 1966. Approach to the study of the degradation of dimethyl
tetrachloroterephthalate. Contributions from Boyce Thompson Institute 23:291-294 (as cited in
HSDB, 2004).
Glotfelty, D.E., A.W. Taylor, B.C. Turner, et al. 1984. Volatilization of surface-applied
pesticides from fallow soil. J. Agric. Food Chem. 32:638-643 (as cited in HSDB, 2004).
Glotfelty, D.E. and C.J. Schomburg. 1989. Volatilization of pesticides from soil. In: Reactions
and Movement of Organic Chemicals in Soils. Soil Sci. Soc. Am. and Am. S. Agron. SSSA
Special Publication 22:181-207 (as cited in HSDB, 2004).
Godek, E.G. 1984. Salmonella/mammalian-microsome plate incorporation mutagenicity assay
(Ames Test) with tetrachloroterephthalic acid. Pharmakon Research international inc. Doc. No.
666-5XT-84-0061-002 (as cited in Michigan Department of Community Health, 2003).
Dacthal Degradates — May, 2008 10-2
-------
Godek, E.G. 1985. Mammalian cell forward mutation assay in the CHO/HGPRT system with
tetrachloroterephthalic acid. Pharmakon Research international inc. Doc. No. 666-5XT-84-0072-
0002 (as cited in Michigan Department of Community Health, 2003).
Gold, L.S., C.B. Sawyer, R. Magaw, et al. 1984. A carcinogenic potency database of the
standardized results of animal bioassays. Environ. Health Perspect. 58:9-319 (as cited in
Klopman et al., 1996).
Gold, L.S., M. de Veciana, G.M. Backman, et al. 1986. Chronological supplement to the
carcinogenic potency database: standardized results of animal bioassays published through
December 1982. Environ. Health Perspect. 67:161-200 (as cited in Klopman et al., 1996).
Gold, L.S., T.H. Sloan, G.M. Backman, et al. 1987. Second chronological supplement to the
carcinogenic potency database: standardized results of animal bioassays published through
December 1984 and by the National Toxicology Program through May 1986. Environ. Health
Perspect. 74:237-329 (as cited in Klopman et al., 1996).
Gold, L.S., T.H. Sloan, G.M. Backman, et al. 1990. Third chronological supplement to the
carcinogenic potency database: standardized results of animal bioassays published through
December 1986 and by the National Toxicology Program through June 1987. Environ. Health
Perspect. 84:215-286 (as cited in Klopman et al., 1996).
Gold, L.S., N.B. Manley, T.H. Sloan, et al. 1993. The fifth plot of the carcinogenic potency
database: results of animal bioassays published in the general literature through 1988 and by the
National Toxicology Program through 1989. Environ. Health Perspect. 100:65-135 (as cited in
Klopman et al., 1996).
Goldenthal, E., F. Wazeter, D. Jessup, et al. 1977. Ninety day toxicity study in rats. Compound:
DTX 76-0010:239-044 [unpublished study]. Prepared by International Research and
Development Corp. Submitted by Diamond Shamrock Agricultural Chemicals. MRTD 00100773
(as cited in U.S. EPA, 1998c, 2004a; Michigan Department of Community Health, 2003).
Gunderson, E.L. 1988. FDA Total Diet Study, April 1982-April 1984. Dietary intakes of
pesticides, selected elements, and other chemicals. J. Assoc. Off. Anal. Chem. 71:1200-1209 (as
cited in HSDB, 2004).
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., et al. 1995. Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. In:
Chihara, H., et al. (eds.). ACS Professional Reference Book. Washington, DC: American
Chemical Society, p. 348 (as cited in HSDB, 2004).
Dacthal Degradates — May, 2008 10-3
-------
Hazleton, L.N. and W.H. Dietedch. 1963. Final report: two-year dietary feeding - dogs
[unpublished study]. MRID 00083584 (as cited in U.S. EPA, 1988b).
Hazleton Laboratories Inc. 1961 [unpublished study]. 28-day dietary feeding study of DAC
1563, DAC 1209 and DAC 876 (as cited in Michigan Department of Community Health, 2003).
Horowitz, M., T. Blumenfeld, G. Herzlinger, et al. 1974. Effects of repeated application often
soil-active herbicides on weed population, residue accumulation and nitrification. Weed Res.
14:97-109 (as cited in HSDB, 2004).
HSDB (Hazardous Substances Data Bank). 2004. Dacthal. Searched December 1, 2004.
Bethesda, MD: National Library of Medicine. Last updated January 31, 1996.
Hurto, K.A., AJ. Turgeon, and M.A. Cole. 1979. Degradation of benefm and DCPA in thatch
and soil from a Kentucky bluegrass (Poapratensis) turf. Weed Soil 27:154-157 (as cited in
HSDB, 2004).
ISK Biotech Corporation. 1990a. MRID 41750103, 41905201. HED Doc. No. 008134, 008444.
Available from EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
ISK Biotech Corporation. 1990b. MRID 41790901. HED Doc. No. 008408. Available from
EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c)
ISK Biotech Corporation. 1991. MRID 41767901. HED Doc. No. 008366. Available from EPA.
Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
ISK Biotech Corporation. 1993. MRID 42731001, 42998401 HED No. 010513. Available from
EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c, 1998c, 2004a).
Jaffe, R., B. Eitzer, E. Stemmler, et al. 1985. Anthropogenic organic compounds in sedentary
fish from Lakes Superior and Huron tributaries. J. Great Lakes Res. 11:156-162 (as cited in
HSDB, 2004).
Jaffe, R. and R.A. Kites. 1986. Anthropogenic, polyhalogenated, organic compounds in
non-migratory fish from the Niagara River area and tributaries to Lake Ontario. J. Great Lakes
Res. 12(1):63-71 (as cited in HSDB, 2004).
Johnson, R.D. and D.D. Manske. 1977. Pesticides in food and feed. Pesticide and other chemical
residues in total diet samples. XL Pestic. Monit. J. 11:116-131 (as cited in HSDB, 2004).
Johnson, R.D., D.D. Manske, and D.S. Podrebarac. 1981. Pesticide, metal, and other chemical
residues in adult total diet samples. XII. August 1975-July 1976. Pestic. Monit. J. 15:54-69 (as
cited in HSDB, 2004).
Dacthal Degradates — May, 2008 10-4
-------
Johnson, R.D., D.D. Manske, D.H. New, et al. 1984. Pesticide, metal, and other chemical
residues in adult total diet samples. XIII. August 1976-September 1977. J. Assoc. Off. Anal.
Chem. 67:154-166 (as cited inHSDB, 2004).
Kazen, C., A. Bloomer, R. Welch, et al. 1974. Persistence of pesticides on the hands of some
occupationally exposed people. Arch. Environ. Health 29:315-318 (as cited in HSDB, 2004).
Klopman, G., D. Fercu, and H.S. Rosenkranz. 1996. The carcinogenic potential of dacthal and its
metabolites. Environ. Toxicol. Chem. 15(2):80-84.
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: http://ca.water.usgs.gov/pnsp/.
Kouri, R., A. Parmar, J. Kuzava, et al. 1977a. The activity of DTX 770006 in the in vivo
cytogenetic assay in rodents for mutagenicity [unpublished study]. Microbiological Associates
Proj. No. T1083. MRID 00107907 (as cited in U.S. EPA, 1988b).
Kouri, R., A. Parmar, J. Kuzava, et al. 1977b. Activity of DTX 770004 in the dominant lethal
assay in rodents for mutagenicity [unpublished study]. Microbiological Associates Proj. No.
T1077. Final Report. MRID 00100775 (as cited in U.S. EPA, 1988b).
Kutz, F.W., A.R. Yobs, and H.S.C. Yang. 1976. National pesticide monitoring networks. In: Lee,
R.E. (ed.). Air Pollution From Pesticides and Agricultural Processes. Cleveland, OH: CRC Press.
pp. 95-136 (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. Available from:
.
Lee, R.E., Jr. 1977. Proceedings of the 4th International Clean Air Congress. Kasuga, S., et al.
(eds). Research Triangle Park, NC: U.S. EPA Health Effects Lab. pp. 37-40 (as cited in HSDB,
2004).
Leiker, T.J., C.E. Rostad, C.R. Barnes, et al. 1991. A reconnaissance study of halogenated
organic compounds in catfish from the lower Mississippi River and its major tributaries.
Chemosphere 23:817-829 (as cited in HSDB, 2004).
Lewis, R.G., R.C. Fortmann, and D.E. Camann. 1994. Evaluation of methods for monitoring the
potential exposure of small children to pesticides in the residential environment. Arch. Environ.
Contam. Toxicol. 26(l):37-46 (as cited in HSDB, 2004).
Dacthal Degradates — May, 2008 10-5
-------
Lyman, W.J., W.F. Reehl, and D.H. Rosenblatt. 1990. Handbook of Chemical Property
Estimation Methods. Washington, DC: American Chemical Society, pp. 4-9 (as cited in HSDB,
2004).
Majewski, M.S., M.M. McChesney, and J.N. Seiber. 1991. A field comparison of two methods
for measuring DCPA soil evaporation rates. Environ. Toxicol. Chem. 10:301-311 (as cited in
HSDB, 2004).
Major, D. 1985. A 30-day oral intubation study in rats with tetrachloroterephthalic acid: SDS
954. Document No. 665-STX-84-0007001 [unpublished study]. MRID 00158011. Prepared by
SDS Biotech Corp. p. 269.(as cited in U.S. EPA, 1998c, 2004a; Michigan Department of
Community Health, 2003).
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: .
Meylan, W.M. and P.H. Howard. 1993. Computer estimation of the atmospheric gas-phase
reaction rate of organic compounds with hydroxyl radicals and ozone. Chemosphere 26:213-218
(as cited in HSDB, 2004).
Michigan Department of Community Health. 2003. Health consultation: Dacthal ground water
contamination, additional toxicological data, Coloma Township, Berrien County Michigan.
Prepared under a Cooperative Agreement with the Agency for Toxic Substance and Disease
Control.
Miller, P.M. and E.D. Gomes. 1974. Detection of DCPA residues in environmental samples.
Pestic. Monit. J. 8:53-58 (as cited in HSDB, 2004).
Mizen, M. 1985. A teratology dose range-finding study in rats with tetrachloroterephthalic acid
(SDS-954) Document No. 687-5Tx-84-0034-002 [unpublished study]. Prepared by SDS Biotech
Corp. p. 120. (MRID 262303 as cited in U.S. EPA, 1998c; MRID 41064802 as cited in U.S.
EPA, 1998c; MRID 00158010 as cited in U.S. EPA, 2004a; Michigan Department of
Community Health, 2003).
Nash, R.G. and TJ. Gish. 1989. Halogenated pesticide volatilization and dissipation from soil
under controlled conditions. Chemosphere 18(ll/12):2353-2362 (as cited in U.S. EPA, 1998c).
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, pp. 238. Available
from: .
Dacthal Degradates — May, 2008 10-6
-------
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 online at:
.
Paynter, O.E. and M. Kundzin. 1963. Two-year dietary administration - rats. Final Report.
MRID 00083577 (as cited in U.S. EPA, 1988b).
Pereira, W.E., F.D. Hostettler, J.R. Cashman, et al. 1994. Occurrence and distribution of
organochlorine compounds in sediment and livers of striped bass (Morone saxatilis) from the
San Francisco Bay-Delta Estuary. Marine Poll. Bull. 28:434-441 (as cited in HSDB, 2004).
Roberts, H.A., et al. 1978. Proc. Br. Crop Prot. Conf. - Weeds 14:87-92 (as cited in HSDB,
2004).
Saiki, M.K. and CJ. Schmitt. 1986. Organochlorine chemical residues in bluegills and common
carp from the irrigated San Joaquin Valley floor, California. Arch. Environ. Contam. Toxicol.
15:357-366 (as cited in HSDB, 2004).
San Sebastian, JR. 1985. in vitro sister chromatid exchange assay in Chinese hamster ovary cells
with tetrachloroterephthalic acid. Pharmakon Research International Inc. Doc. No. 666-5XT-84-
0062-002. (as cited in Michigan Department of Community Health, 2003).
Schattenberg, HJ. Ill and J-P. Hsu. 1992. Pesticide residue survey of produce from 1989 to
1991. J. AOAC Int. 75:925-933 (as cited in HSDB, 2004).
Schmitt, C.J., J.L. Zajicek, and M.A. Ribick. 1985. National pesticide monitoring program:
residues of organochlorine chemicals in freshwater fish, 1980-81. Arch. Environ. Contam.
Toxicol. 14:225-260 (as cited in HSDB, 2004).
Schmitt, C.J., J.L. Zajicek, and P.H. Peterman. 1990. National Contaminant Biomonitoring
Program: residues of organochlorine chemicals in USA freshwater fish, 1976-1984. Arch.
Environ. Contam. Toxicol. 19:748-781 (as cited in HSDB, 2004).
SDS Biotech Corporation. 1986. MRID 00160685. HED Doc. No. 005866, 009515. Available
from EPA. Write to FOI, EPA, Washington, DC 20460 (as cited in U.S. EPA, 1994c).
Siou, G. 1985. The micronucleus test in mice with tetrachloroterephthalic acid. Experimental
Cytology and Research in industrial Toxicology, Histopathology Laboratory, Versailles France:
Dacthal Degradates — May, 2008 10-7
-------
Doc. No. 666=5X1-84-0071-002. (as cited in Michigan Department of Community Health,
2003).
Skinner, M.B. and D.E. Stallard. 1963. Dacthal animal metabolism studies. MRID 000835791 (as
cited in U.S. EPA, 1988b).
Spencer, E.Y. 1982. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093.
Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, p. 126 (as cited in
HSDB, 2004).
Starr, H.G. Jr, F.D. Aldrich, W.D. MacDougall III, et al. 1974. Contribution of household dust to
the human exposure to pesticides. Pestic. Monit. J. 8:209-212 (as cited in HSDB, 2004).
Swann, R.L., D.A. Laskowski, PJ. McCall, et al. 1983. A rapid method for the estimation of the
environmental parameters octanol/water partition coefficient, soil sorption constant, water to air
ratio and water solubility. Res. Rev. 85:17-28 (as cited in HSDB, 2004).
Tessari, J.D. and D.L. Spencer. 1971. Air sampling for pesticides in the human environment. J.
AOAC Int. 54:1376-1382 (as cited in HSDB, 2004).
Tomlin, C. 1994. The Pesticide Manual - A World Compendium. 10th ed. Thornton Heath, UK:
The British Crop Protection Council, p. 205 (as cited in HSDB, 2004).
Tusing, T.W. 1963. Oral administration - humans. MRID 0083583 (as cited in U.S. EPA,
1988b).
Tweedy, E.G., N. Turner, and M. Achituv. 1968. The interactions of soil-borne microorganisms
and DCPA. Weed Sci. 16:470-473 (as cited in HSDB, 2004).
U.S. EPA (United States Environmental Protection Agency). 1986a. Guidelines for the health
risk assessment of chemical mixtures. Fed. Reg. 51(185):34014-34025. Available from:
.
U.S. EPA (United States Environmental Protection Agency). 1986b. Guidelines for mutagenicity
risk assessment. Fed. Reg. 51(185):34006-34012.
U.S. EPA (United States Environmental Protection Agency). 1986c. Guidelines for carcinogen
risk assessment. Fed. Reg. 51(185):33992-34003.
U.S. EPA (United States Environmental Protection Agency). 1988a. 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.
Confidential Business Information submitted to the EPA Office of Pesticide Programs.
Dacthal Degradates — May, 2008 10-8
-------
U.S. EPA (United States Environmental Protection Agency). 1988b. DCPA (Dacthal) Health
Advisory. Office of Drinking Water, U.S. Environmental Protection Agency. August, 1988.
U.S. EPA (United States Environmental Protection Agency). 1988c. Hexachlorobenzene
(CASRN 118-74-1). Integrated Risk Information System (IRIS). Office of Research and
Development. Available from: http://www.epa.gov/iris/subst/0374.htm.
U.S. EPA (United States Environmental Protection Agency). 1991. Guidelines for
developmental toxicity risk assessment. Fed. Reg. 56(234):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(206):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). 1994c. Integrated Risk Information
System (IRIS): Dacthal. Cincinnati, OH.
U.S. EPA (United States Environmental Protection Agency). 1995a. 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, Springfield, VA; PB95-213765, and
.
U.S. EPA (United States Environmental Protection Agency). 1995b. Carcinogenicity peer review
of DCPA (dimethyl tetrachloroterephthalate or dacthal). U. S. Environmental Protection Agency.
Office of Pesticide Programs TXR # 0050123. February 10, 1995.
U.S. EPA (United States Environmental Protection Agency). 1996a. Exposure Factors
Handbook. U.S. Environmental Protection Agency, Office of Research and Development,
Washington, DC. EPA/600/8-89/043.
U.S. EPA (United States Environmental Protection Agency). 1996b. Guidelines for reproductive
toxicity risk assessment. Fed. Reg. 61(212):56274-56322.
U.S. EPA (United States Environmental Protection Agency). 1997. Announcement of the draft
drinking water contaminant candidate list; notice. Fed. Reg. 62(193):522194-52219.
U.S. EPA (United States Environmental Protection Agency). 1998a. Guidelines for neurotoxicity
risk assessment. Fed Reg 63(93):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
Dacthal Degradates — May, 2008 10-9
-------
Development, Washington, DC. EPA 100-B-98-001. Available from: National Technical
Information Service, Springfield, VA; PB98-140726, and
.
U.S. EPA (United States Environmental Protection Agency). 1998c. Reregi strati on eligibility
decision DCPA. Washington, DC: Office of Prevention, Pesticides, and Toxic Substances
(7508C), EPA738-R-98-005. November 1998.
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.
Reg67(106):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. TPA
(tetrachloroterephthalic acid)-metabolite of DCPA (Dacthal). Evaluation of potential for
carcinogenicity. U.S. Environmental Protection Agency Office of Prevention, Pesticide, and
Toxic Substances, Washington, DC 20460. May 25, 2004.
Dacthal Degradates — May, 2008 10-10
-------
U.S. EPA (United States Environmental Protection Agency). 2004b. 2nd Revised drinking water
and aggregate human health risk assessment for Chlorothal demethyl (DCPA) and the metabolite
tetrachloroterephthalic acid (TPA) DP Barcode D 291641. Washington, DC 20460. June 8, 2004.
U.S. EPA (United States Environmental Protection Agency). 2004c. 2004 Edition of the
Drinking Water Standards and Health Advisories. EPA 822-R-04-005. Office of Water. Winter.
Available from: .
U.S. EPA (United States Environmental Protection Agency). 2005a. 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). 2005b. DCPA: Order to terminate
uses. Fed. Reg. 70(143):43408-43410.
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.
U.S. FDA (United States Food and Drug Administration). 2003. Food and Drug Administration
total diet study: Sullary of residues found ordered by pesticide (Market Baskets 91-3 to 01-4).
June.
USGS (United States Geological Survey). 2001. Summary publications from 51 NAWQA study
units sampled in 1991-2001. Available from: .
Wazeter, F.X., E.I. Goldenthal, and W.P. Dean. 1974a. Acute oral toxicity (LD50) male and
female albino rats [unpublished study]. MRID 000318721 (as cited in U.S. EPA, 1988b).
Wazeter, F.X., E.I. Goldenthal, and W.P. Dean. 1974b. Acute oral toxicity (LD50) in beagle dogs
[unpublished study]. MRID 00031873J (as cited in U.S. EPA, 1988b).
Wettasinghe, A., and I.J. Tinsley 1993. Degradation of dacthal and its metabolites in soil. Bull.
Environ. Contam. Toxicol. 50:226-231 (as cited inHSDB, 2004).
Whitmore, R.W., F.W. Immerman, D.E. Camann, et al. 1994. Non-occupational exposures to
pesticides for residents of two U.S. cities. Arch. Environ. Contam. Toxicol. 26:47-59 (as cited in
HSDB, 2004).
Worthing, C.R. (ed.). 1979. Pesticide Manual. 6th ed. Worcestershire, England: British Crop
Protection Council, p. 121 (as cited in HSDB, 2004).
Confidential Business Information submitted to the Office of Pesticide Programs.
Dacthal Degradates — May, 2008 10-11
-------
Dacthal Degradates — May, 2008 10-12
-------
APPENDIX A: Abbreviations
BCF
CCL
CWS
DCPA
FR
GC/EC
gd
HCB
HRL
Koc
Kow
LOAEL
LOD
MRL
MTP
MULTICASE
NAWQA
y4-NBP
NDWAC
NOAEL
NPDWR
NTNCWS
NTP
OPP
ppb
ppm
PWS
QSAR
RED
RfC
RfD
RL
RSC
SDWA
TPA
TSH
UCMR1
USDA
U.S. EPA
U.S. FDA
USGS
bioconcentration factor
Contaminant Candidate List
community water system
dimethyl tetrachloroterephthalic acid
Federal Register
gas chromatography/electron capture
gestation days
hexachl orob enzene
health reference level
organic carbon/water partitioning coefficient
octanol-water partitioning coefficient
lowest observed adverse effect level
limits of detection
minimum reporting level
monomethyl tetrachloroterephthalic acid
multiple computer automated structure evaluation
National Water Quality Assessment
Y-4-nitrobenzylpyridine
National Drinking Water Advisory Council
no observed adverse effect level
National Primary Drinking Water Regulation
nontransient noncommunity water system
National Toxicology Program
Office of Pesticide Programs (U.S. EPA)
parts per billion
parts per million
public water system
quantitative structure-activity relationship
Re-registration Eligibility Decision
reference concentration
reference dose
reporting level
relative source contribution
Safe Drinking Water Act
triiodothyronine
thyroxine
tetrachloroterephthalic acid
thyroid-stimulating hormone
first Unregulated Contaminant Monitoring Regulation
United States Department of Agriculture
United States Environmental Protection Agency
United States Food and Drug Administration
United States Geological Survey
Dacthal Degradates — May, 2008
Appendix A-l
------- |