United States
Environmental Protection
Agency
Health Effects Support
Document for Fonofos
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Health Effects Support Document
for
Fonofos
U.S. Environmental Protection Agency
Office of Water (43 04T)
Health and Ecological Criteria Division
Washington, DC 20460
www.epa.gov/safewater/ccl/pdf/fonofos.pdf
EPA Document Number: 822-R-08-009
January, 2008
Printed on Recycled Paper
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Fonofos January, 2008 IV
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FOREWORD
The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator
of the Environmental Protection Agency (EPA) to establish a list of contaminants to aid the
Agency in regulatory priority setting for the drinking water program. In addition, the SDWA
requires EPA to make regulatory determinations for no fewer than five contaminants by August
2001 and every five years thereafter. The criteria used to determine whether or not to regulate a
chemical on the Contaminant Candidate List (CCL) are the following:
The contaminant may have an adverse effect on the health of persons.
The contaminant is known to occur or there is a substantial likelihood that the
contaminant will occur in public water systems with a frequency and at levels of
public health concern.
In the sole judgment of the Administrator, regulation of such contaminant presents a
meaningful opportunity for health risk reduction for persons served by public water
systems.
The Agency's findings for all three criteria are used in making a determination to
regulate a contaminant. The Agency may determine that there is no need for regulation when a
contaminant fails to meet one of the criteria. The decision not to regulate is considered a final
Agency action and is subject to judicial review.
This document provides the health effects basis for the regulatory determination for
fonofos. In arriving at the regulatory determination, The Office of Water used the Re-
registration Eligibility Decision document (RED) for fonofos published by the Office of
Pesticides Programs (OPP) as well as any OPP health assessment documents that supported the
RED. The following publications from OPP were used in development of this document.
U.S. EPA (United States Environmental Protection Agency). 1999a. RED facts: O-Ethyl
S-phenylethylphosphonodithiolate (Fonofos). EPA 738-F-99-019. U.S. Environmental
Protection Agency, Prevention, Pesticides and Toxic Substances. Available from:
.
Information from the OPP risk assessment was supplemented with information from the
primary references for key studies where they have been published and recent studies of fonofos
identified in a literature search conducted in 2004 and updated in 2007.
A Reference Dose (RfD) is provided as the assessment of long-term toxic effects other
than carcinogenicity. RfD determination assumes that thresholds exist for certain toxic effects,
such as cellular necrosis, significant body or organ weight changes, blood disorders, etc. It is
expressed in terms of milligrams per kilogram per day (mg/kg-day). In general, the RfD is an
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.
Fonofos January, 2008
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The carcinogenicity assessment for fonofos includes a formal hazard identification and
an estimate of tumorigenic potency when available. Hazard identification is a weight-of-
evidence judgment of the likelihood that the agent is a human carcinogen via the oral route and
of the conditions under which the carcinogenic effects may be expressed.
Development of these hazard identification and dose-response assessments for fonofos
has followed the general guidelines for risk assessment as set forth by the National Research
Council (1983). EPA guidelines that were used in the development of this assessment may
include the following: Guidelines for the Health Risk Assessment of Chemical Mixtures (U.S.
EPA, 1986a), Guidelines for Mutagenicity Risk Assessment (U.S. EPA, 1986b), Guidelines for
Developmental Toxicity Risk Assessment (U.S. EPA, 1991), Guidelines for Reproductive Toxicity
Risk Assessment (U.S. EPA, 1996a), Guidelines for Neurotoxicity Risk Assessment (U.S. EPA,
1998a), Guidelines for Carcinogen Assessment (U.S. EPA, 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 (U.S.
EPA, 1994a), Methods for Derivation of Inhalation Reference Concentrations and Application of
Inhalation Dosimetry (U.S. EPA, 1994b), Use of the Benchmark Dose Approach in Health Risk
Assessment (U.S. EPA, 1995), Science Policy Council Handbook: Peer Review (U.S. EPA,
1998b, 2000a), Science Policy Council Handbook: Risk Characterization (U.S. EPA, 2000b),
Benchmark Dose Technical Guidance Document (U.S. EPA, 2000c), Supplementary Guidance
for Conducting Health Risk Assessment of Chemical Mixtures (U.S. EPA, 2000d), and^4 Review
of the Reference Dose and Reference Concentration Processes (U.S. EPA, 2002a).
The chapter on occurrence and exposure to fonofos through potable water was developed
by the Office of Ground Water and Drinking Water. It is based primarily on first Unregulated
Contaminant Monitoring Regulation (UCMR1) data collected under the SDWA. The UCMR1
data are supplemented with ambient water data, as well as data from the States, and published
papers on occurrence in drinking water.
Fonofos January, 2008 VI
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ACKNOWLEDGMENT
This document was prepared under the U.S. EPA contract No. 68-C-02-009, Work
Assignment No. 2-54 and 3-54 with ICF Consulting, Fairfax, VA. The Lead U.S. EPA Scientist
is Amal Mourad Mahfouz, Ph.D., Health and Ecological Criteria Division, Office of Science and
Technology, Office of Water.
Fonofos January, 2008 Vll
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Fonofos January, 2008 Vlll
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TABLE OF CONTENTS
FOREWORD v
ACKNOWLEDGMENT vii
LIST OF TABLES xii
LIST OF FIGURES xiv
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 3-3
4.0 EXPOSURE FROM DRINKING WATER 4-1
4.1 Introduction 4-1
4.2 Ambient Occurrence 4-1
4.2.1 Data Sources and Methods 4-1
4.2.2 Results 4-3
4.3 Drinking Water Occurrence 4-4
4.3.1 Data Sources, Data Quality, and Analytical Methods 4-4
4.3.2 CCL Health Reference Level 4-4
4.3.3 Results 4-5
4.4 Summary 4-8
5.0 EXPOSURE FROM MEDIA OTHER THAN WATER 5-1
5.1 Exposure from Food 5-1
5.1.1 Concentration in Non-Fish Food Items 5-1
5.1.2 Concentrations in Fish and Shellfish 5-1
5.1.3 Intake of Fonofos from Food 5-1
5.2 Exposure from Air 5-1
5.2.1 Concentration of Fonofos in Air 5-1
5.2.2 Intake of Fonofos from Air 5-2
5.3 Exposure from Soil 5-2
5.3.1 Concentration of Fonofos in Soil 5-2
5.3.2 Intake of Fonofos from Soil 5-2
5.4 Summary 5-2
6.0 HAZARD AND DOSE-RESPONSE ASSESSMENT 6-1
6.1 Characterization of Hazard 6-1
Fonofos January, 2008 IX
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6.1.1 Synthesis and Evaluation of Major Noncancer Effects 6-1
6.1.2 Synthesis and Evaluation of Carcinogenic Effects and Mode of Action
6-3
6.1.3 Weight of Evidence Evaluation for Carcinogenicity 6-3
6.1.4 Potentially Sensitive Populations 6-3
6.2 Reference Dose 6-4
6.2.1 Choice of Principle Study and Critical Effect 6-4
6.2.2 Method of Analysis 6-4
6.3 Carcinogen Assessment 6-5
6.4 Sensitive Population Considerations 6-5
6.5 Post Re-registration Health Effects Publications 6-5
6.6 CCL Health Reference Level 6-5
7.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK
FROM DRINKING WATER 7-1
7.1 Regulatory Determination for Chemicals on the CCL 7-1
7.1.1 Criteria for Regulatory Determination 7-1
7.1.2 National Drinking Water Advisory Council Recommendations 7-2
7.2 Health Effects 7-2
7.2.1 Health Criterion Conclusion 7-2
7.2.2 Hazard Characterization and Mode of Action Implications 7-3
7.2.3 Dose-Response Characterization and Implications in Risk Assessment
7-3
7.3 Occurrence in Public Water Systems 7-4
7.3.1 Occurrence Criterion Conclusion 7-5
7.3.2 Monitoring Data 7-5
7.3.3 Use and Fate Data 7-6
7.4 Risk Reduction 7-6
7.4.1 Risk Criterion Conclusion 7-6
7.4.2 Exposed Population Estimates 7-7
7.4.3 Relative Source Contribution 7-7
7.4.4 Sensitive Populations 7-7
7.5 Regulatory Determination Decision 7-7
8.0 REFERENCES 8-1
APPENDIX A: Abbreviations and Acronyms Appendix A-l
Fonofos January, 2008
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LIST OF TABLES
Table 2-1 Chemical and Physical Properties of Fonofos 2-2
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of Fonofos in
Ambient Surface Water, 1992-2001 4-3
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of Fonofos in
Ambient Ground Water, 1992-2001 4-4
Table 4-3 Summary UCMR1 Occurrence Statistics for Fonofos in Small Systems 4-6
Table 4-4 Summary UCMR1 Occurrence Statistics for Fonofos in Large Systems 4-7
Fonofos January, 2008 XI
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Fonofos January, 2008 Xll
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LIST OF FIGURES
Figure 2-1 Chemical Structure of Fonofos 2-1
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Fonofos January, 2008 XIV
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1.0 EXECUTIVE SUMMARY
The U.S. Environmental Protection Agency (EPA) has prepared this Health Effects
Support Document for Fonofos to support a determination regarding whether to regulate fonofos
with a National Primary Drinking Water Regulation (NPDWR). The available data on
occurrence, exposure, and other risk considerations suggest that, because fonofos does not occur
in public water systems at frequencies and levels of public health concern, regulating fonofos
will not present a meaningful opportunity to reduce health risk. EPA will present a
determination and further analysis in the Federal Register Notice covering the CCL proposals.
Fonofos is an organophosphate used as a soil insecticide against insect pests on a variety
of agricultural crops, vegetables, and fruits. It is a clear, light yellow liquid with an aromatic
odor. Production of fonofos was cancelled on May 6, 1998 (63 Federal Register [FR] 25033),
with an effective date of November 2, 1998, plus a one-year grace period to permit the
exhaustion of existing stocks before the end of 1999.
Fonofos, like many organophosphates, is toxic to humans and animals. Case human
poisoning reports and acute oral toxicity studies in animals indicate that oral exposure to fonofos
induces clinical signs of toxicity that are typical of cholinesterase inhibitors. Accidental
ingestion of fonofos by humans results in signs and symptoms of acute intoxication, including
muscarinic, nicotinic, and central nervous system (CNS) manifestations. Acute oral toxicity
studies in animals reported clinical signs such as depression, tremors, salivation, diarrhea, and
labored breathing.
Organophosphates irreversibly bind to cholinesterase, causing the phosphorylation and
deactivation of acetylcholinesterase. The subsequent accumulation of acetylcholine at the neural
synapse causes an initial overstimulation, followed by eventual exhaustion and disruption of
postsynaptic neural transmission in the central nervous system and peripheral nervous systems.
This effect is the critical endpoint of concern for fonofos as noted in the animal studies in hens,
rats, and dogs. Consequently, these studies were used to establish the no observed adverse effect
level (NOAEL) for this critical endpoint of toxicity and to calculate the reference dose (RfD) for
fonofos.
Fonofos is classified as not likely to be carcinogenic to humans because there is no
evidence of carcinogenic potential in the available long-term feeding studies in rats and mice.
The RfD is 0.002 mg/kg/day and is based on a one-year dog feeding study where animals
exhibited cholinesterase inhibition. This RfD was used to calculate the drinking water health
reference level (FtRL) for fonofos at 0.01 mg/L. This value also is protective of children, as the
sensitive population of potential concern, because it used an RfD based on an NOAEL that is
below the level where developmental effects occurred.
Drinking water monitoring of fonofos was conducted under the first Unregulated
Contaminant Monitoring Regulation (UCMR1). As a List 2 contaminant, fonofos was scheduled
to be monitored by 300 public water systems. Data were received from 295 systems. The data
have been analyzed at three levels as follows: level of simple detections (>minimum reporting
limit, >MRL, or >0.5 |ig/L), at the level of exceedances of the HRL (>HRL, or >10 |ig/L), and
Fonofos January, 2008 1-1
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at the level of exceedances of one-half the value of the HRL (>/^>HRL, or >5 |ig/L). No
detections of fonofos were found in any samples, and thus there were no exceedances of the
HRL or one-half the HRL.
It appears that the general population is not exposed to fonofos through water
consumption or use. Therefore, the impact of regulating fonofos concentrations in drinking
water on health risk reduction is likely to be small. Regulation of fonofos in public water
systems does not appear to present a meaningful opportunity for health risk reduction.
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2.0 IDENTITY: CHEMICAL AND PHYSICAL PROPERTIES
Fonofos is a clear, light yellow liquid with an aromatic odor. It also is flammable and
corrosive to steel. The compound exists in two chiral forms which are interconverted in
solutions of carbon tetrachloride, cyclohexane, and methanol. The (R)-isomer is more toxic to
insects and mice and a stronger inhibitor of cholinesterase than the (S)-isomer (HSDB, 2004).
Commercially, fonofos once was available in granules or as an emulsifiable concentrate
with a wide range of percent active ingredient. Commercial fonofos preparations were sold
under the Dyfonate trade name (U.S. EPA, 1999a). The manufacturer voluntarily withdrew
fonofos from the market, and it is not a commercially available pesticide in the United States
(U.S. EPA, 1998c, 1999b).
Figure 2-1 Chemical Structure of Fonofos
Source: Chemfinder (2004)
The chemical structure of fonofos is shown above (Figure 2-1). Its physical and
chemical properties and other reference information are listed in Table 2-1.
Fonofos January, 2008 2-1
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Table 2-1 Chemical and Physical Properties of Fonofos
Property
Chemical Abstracts Registry
(CAS) No.
EPA Pesticide Chemical Code
Synonyms
Registered Trade Name(s)
Chemical Formula
Molecular Weight
Physical State
Boiling Point
Melting Point
Density (at 20ฐC)
Vapor Pressure:
At 20 ฐC
At 25ฐC
Partition Coefficients:
Log Kow
Log Koc
Solubility in:
Water
Other Solvents
Conversion Factors
(at 25 ฐC, 1 atm)
Information
944-22-9
041701
difonate; difonatal;
dyfonateฎ; ENT 25;
fonophos; stauffer N2790
dyfonate; ENT-25, 796;
stauffer -2790; -2790
C10H15OPS2
246.32
light yellow liquid
130ฐC
No data
1.16at25ฐC
No data
3.38xlO-4mmHg
3.94
1.18-3.03
15.7 mg/L (20ฐC)
Acetone, Ethanol, Kerosene,
Methyl isobutyl ketone,
Xylene
1 ppm= 10.074 mg/m3
1 mg/m3= 0.0993 ppm
Source(s): U.S. EPA (1989); HSDB (2004)
Fonofos January, 2008
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3.0 USES AND ENVIRONMENTAL FATE
3.1 Production and Use
Fonofos is produced by reacting thiophenol with O-ethyl ethyl or using
phosphonochloridothioate (HSDB, 2004). It was used as a soil insecticide against insect pests
(worms, maggots, flies, and crickets) on a variety of agricultural crops, vegetables and fruits
(U.S. EPA, 1999a).
Fonofos was scheduled for a re-registration decision in 1999. However, before the
review was completed, the registrant requested voluntary cancellation. The cancellation was
announced in the Federal Register on May 6, 1998 (63 Federal Register [FR] 25033), with an
effective date of November 2, 1998, plus a one-year grace period to permit the exhaustion of
existing stocks before the end of 1999 (U.S. EPA, 1999a).
3.2 Environmental Release
Cancellation of the fonofos registration limited its potential to contaminate the
environment through agricultural uses.
3.3 Environmental Fate
Fonofos was usually applied directly to the soil. Fonofos is moderately mobile to
essentially immobile in soil with Freundlich Kads (adsorption coefficient that most closely fits
empirical data) values ranging from 3-13 mL/g (U.S. EPA, 1999a). It has a wide range of
organic carbon partitioning coefficient (Koc) values estimated to be 68 (Log Koc = 1.83) (Swann
et al., 1983) to 5,128 (Rao et al., 1985); these values provide little predictive information on the
affinity of fonofos for organic carbon. Koc values ranging from 50 to 150 (equivalent to log Koc
values of 1.7 and 2.18, respectively) are expected to be highly mobile in carbon rich
environments, whereas, values greater than 3.7 indicate a compound could be relatively
immobile. Laboratory and field leaching studies indicate that fonofos has low to very low
mobility in highly carbon rich soils such as silt loam, sandy loam, and organic soil, but is
relatively mobile in quartz sand (Lichtenstein et al., 1972; Chapman et al., 1984; Lichtenstein
and Liang, 1987). Therefore, it can be assumed from experimental data that fonofos binds to
highly carbon rich soils. The adsorption of fonofos increases with decreasing temperature and
increasing organic content, particularly humic acid and an associated cation content of soil
(Choudhry, 1983). A certain fraction of both fonofos and its oxon metabolite form bound
residues in soil and the latter fraction increases with time (Khan and Belanger, 1987).
Fonofos may volatilize from moist soils and exist in the vapor phase as evident from its
estimated Henry's Law constant of 7.0 x 10"6 atm-m3/mole, which was based on its vapor
pressure and water solubility constants of 3.38 X 10"4 mm Hg (USDA, 2003) and 15.7 mg/L
(Yalkowsky and He, 2003), respectively. In a laboratory volatility study, approximately 35% of
the fonofos that was applied to soil volatilized after 24 hours; most of the remaining fonofos was
extractable from soil (U.S. EPA, 1999a). In another study, volatilization losses of fonofos were
almost twice the rate from no-till agricultural soils (6.1%) compared with conventional tilled
Fonofos January, 2008 3-1
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soils (4.0%) following application of 530 mg/m2, measured over 26 days. Volatilization rates
quickly decreased when compared to loss of total fonofos suggesting adsorption to soil (Whang
etal., 1993).
Adsorption to highly carbon rich soils may attenuate the volatilization of fonofos.
Estimated and experimental soil half-lives of 120 and 150 days (Johnson, 1991) and 121-133
days (U.S. EPA, 1999a) under aerobic and anaerobic conditions, respectively, indicate that
biodegradation may be an important environmental fate process in soil. Fonofos' major route of
degradation in the soil is biodegradation (Miles et al., 1979). The conditions of the environment
and soil will affect the half-life of fonofos in a field as shown by three studies that determined
the half-lives of the compound to range from 18-82 days (Racke, 1992; Huckins et al., 1986;
Miles et al., 1979).
The major metabolite of biodegradation in fonofos-treated soil is carbon dioxide;
dyphonate-oxon, methyl phenyl sulfone, and other unidentified polar products are minor
metabolites (Racke and Coats, 1988). The degradates of fonofos, fonofos oxon, and
methylphenyl sulfone were very mobile to moderately mobile in soil with Freundlich Kads values
of 0.66-3.3 mL/g and 0.05-66 ml/g, respectively (U.S. EPA, 1999a).
Fonofos is only slightly soluble in water (15.7 mg/L) and is therefore not expected to
migrate into water rapidly following soil application. Fonofos may adsorb onto organic material
in water systems such as suspended solids and sediment as observed in moist high carbon rich
soils. Fonofos may volatilize from water surfaces, but the process will be slowed by adsorption
to organic material. Fonofos was stable to hydrolysis with a range of half-lives of 128-435 days
(U.S. EPA, 1999a). Estimated volatilization half-lives for a model river and model lake are 8
and 66 days, respectively, and from a model pond is 2.3 yrs if adsorption is considered (U.S.
EPA, 1987). The hydrolysis half-lives of fonofos in water at 25ฐC and pH 5, 6, 7 and 8 were 50,
41, 22 and 6.9 weeks, respectively (Chapman and Cole, 1982); however, at pH 5 in the presence
of cupric ion, a catalytic accelerator, the half-life was less than 1 day (Chapman and Harris,
1984). Fonofos may undergo photodegradation; in the presence of anthraquinone (electron
transfer agent involved in photosynthesis), this process is complete in 1 hr (Ivie and Casida,
197la). Other compounds that significantly photosensitized dyphonate were anthracene,
rotenone and chloroplasts (Ivie and Casida, 1971a,b). Photosensitizers such as rotenone and
chloroplasts that occur naturally in some plants may enhance photodegradation of fonofos (Ivie
and Casida, 1971b).
Fonofos does not bioaccumulate significantly in fish. For example, the mosquito fish
(Gambusia a/finis) had a bioaccumulation factor (BCF) of less than 2 (Metcalf, 1977). A BCF
of 300 for whole fish and 140 for the edible tissues was observed in another study however, 90%
depuration was observed within 14 days (U.S. EPA, 1999a). There is evidence that aquatic
organisms readily metabolize organophosphates (Freed et al., 1976), and they can be altered
chemically (Boethling and Mackay, 2000) once released into the environment to make them less
bioavailable.
According to a model of gas/particle partitioning of semivolatile organic compounds in
the atmosphere (Bidleman, 1988) and the vapor pressure of fonofos (3.38 x 10"4 mm Hg at 25ฐC)
Fonofos January, 2008 3-2
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(USDA, 2003), fonofos was determined to exist in both the vapor and particulate phases in the
ambient atmosphere. Fonofos in the vapor-phase is degraded by photochemically-produced
hydroxyl radical reactions; the half-life for this reaction in air is estimated to be 4.5 hrs, based on
calculations from its rate constant of 8.9 x 10"11 cm3/molecule-sec at 25ฐC (Atkinson, 1988).
Fonofos in the particulate phase may be removed from the air by wet or dry deposition. Some
photodegradation was observed when fonofos was deposited on silica gel chromatoplates and
exposed to sunlight (Ivie and Casida, 197la). This corresponds to an atmospheric half-life of
about 4.5 hours at an atmospheric concentration of 5 x 10+5 hydroxyl radicals/cm3 (Meylan and
Howard, 1993).
3.4 Summary
Fonofos has been released directly to the environment in the past, based on its historic
use as a direct soil insecticide in the U.S. Upon release into the soil, fonofos is expected to have
very high to no mobility based on the large range of Koc values of 68 to 5,128 (equivalent to log
Koc values of 1.83 and 3.7, respectively); however, fonofos has demonstrated that it binds to
highly carbon rich soils and is relatively mobile in soils with quartz content. Fonofos adsorbs
onto soils more readily with decreasing temperature and increasing organic content, particularly
humic acid and associated cation content. Fonofos is expected to volatilize from moist soil
surfaces based upon the estimated Henry's Law constant of 7.0 x 10"6 atm-m3/mole, but
adsorption may attenuate volatilization. Estimated soil half-lives of 120 and 150 days under
aerobic and anaerobic conditions, respectively, indicate that biodegradation may be an important
environmental fate process in soil as opposed to volatilization.
Fonofos in ambient air will exist in both the vapor and particulate phases as expected
from the vapor pressure at 25ฐC of 3.38 x 10"4 mm Hg. The vapor-phase fonofos will undergo
reactions with photochemically-produced hydroxyl radicals with an estimated half-life of 4.5 hrs.
Wet and dry deposition is expected to remove particulate-phase fonofos from the atmosphere.
Fonofos in the water systems may adsorb to carbon-rich particles, suspended solids, and
sediment as predicted by the upper-end Koc values.
Volatilization from water surfaces is expected to be an important fate process based upon
the estimated Henry's Law constant. Estimated volatilization half-lives for a model river and
model lake are 8 and 66 days, respectively. As with volatilisation for moist soils, volatilization
from water surfaces may be attenuated by adsorption to suspended solids and sediment in the
water column. The estimated volatilization half-life from a model pond was 2.3 years when
adsorption was considered. The reported hydrolysis half-live range is 110-435 days indicating
the relative stability of fonofos to this process.
The available data indicate that fonofos does not bioconcentrate extensively in fish.
Although an estimated BCF of 300 was reported for whole fish in one study, the compound was
found to be metabolized in tissues at a later time, indicating a lower potential for accumulation.
Aquatic organisms readily metabolize organophosphates and upon release into the water they
can be altered abiotically; thus, the BCF potential is mitigated by these factors.
Fonofos January, 2008 3-3
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4.0 EXPOSURE FROM DRINKING WATER
4.1 Introduction
EPA used data from several sources to evaluate the potential for occurrence of fonofos in
Public Water Systems (PWSs). The primary source of drinking water occurrence data for
fonofos was the first Unregulated Contaminant Monitoring Regulation (UCMR1) program. The
Agency also evaluated ambient water quality data from the United States Geological Survey
(USGS).
4.2 Ambient Occurrence
4.2.1 Data Sources and Methods
USGS instituted the National Water Quality Assessment (NAWQA) program in 1991 to
examine ambient water quality status and trends in the United States. NAWQA is designed to
apply nationally consistent methods to provide a consistent basis for comparisons among study
basins across the country and over time. These occurrence assessments serve to facilitate
interpretation of natural and anthropogenic factors affecting national water quality. For more
detailed information on the NAWQA program design and implementation, please refer to Leahy
and Thompson (1994) and Hamilton and colleagues (2004).
Study Unit Monitoring
The NAWQA program conducts monitoring and water quality assessments in significant
watersheds and aquifers referred to as "study units." NAWQA's sampling approach is not
"statistically" designed (i.e., it does not involve random sampling), but it provides a
representative view of the nation's waters in its coverage and scope. Together, the 51 study
units monitored between 1991 and 2001 include the aquifers and watersheds that supply more
than 60% of the nation's drinking water and water used for agriculture and industry (NRC,
2002). NAWQA monitors the occurrence of chemicals such as pesticides, nutrients, volatile
organic compounds (VOCs), trace elements, and radionuclides, and the condition of aquatic
habitats and fish, insects, and algal communities (Hamilton et al., 2004).
Monitoring of study units occurs in stages. Between 1991 and 2001, approximately one-
third of the study units at a time were studied intensively for a period of three to five years,
alternating with a period of less intensive research and monitoring that lasted between five and
seven years. Thus, all participating study units rotated through intensive assessment in a ten-
year cycle (Leahy and Thompson, 1994). The first ten-year cycle was called "Cycle 1."
Summary reports are available for the 51 study units that underwent intensive monitoring in
Cycle 1 (USGS, 2001). Cycle 2 monitoring is scheduled to proceed in 42 study units from 2002
to 2012 (Hamilton et al., 2004).
Fonofos January, 2008 4-1
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Pesticide National Synthesis
Through a series of National Synthesis efforts, the USGS NAWQA program is preparing
comprehensive analyses of data on topics of particular concern. These data are aggregated from
the individual study units and other sources to provide a national overview.
The Pesticide National Synthesis began in 1991. Results from the most recent USGS
Pesticide National Synthesis analysis, based on complete Cycle 1 (1991-2001) data from
NAWQA study units, are posted on the NAWQA Pesticide National Synthesis website (Martin
et al., 2003; Kolpin and Martin, 2003; Nowell, 2003; Nowell and Capel, 2003). USGS considers
these results to be provisional. Data for surface water, ground water, bed sediment, and biota are
presented separately, and results in each category are subdivided by land use category. Land use
categories include agricultural, urban, mixed (deeper aquifers of regional extent in the case of
ground water), and undeveloped. The National Synthesis analysis for pesticides is a first step
toward the USGS goal of describing the occurrence of pesticides in relation to different land use
and land management patterns, and developing a deeper understanding of the relationship
between spatial occurrence of contaminants and their fate, transport, persistence, and mobility
characteristics.
The surface water summary data presented by USGS in the Pesticide National Synthesis
(Martin et al., 2003) only include stream data. Sampling data from a single one-year period,
generally the year with the most complete data, were used to represent each stream site. Sites
with few data or significant gaps were excluded from the analysis. NAWQA stream sites were
sampled repeatedly throughout the year to capture and characterize seasonal and hydrologic
variability. In the National Synthesis analysis, the data were time-weighted to provide an
estimate of the annual frequency of detection and occurrence at a given concentration.
The USGS Pesticide National Synthesis only analyzed ground water data from wells;
data from springs and agricultural tile drains were not included. The sampling regimen used for
wells was different than that for surface water. In the National Synthesis analysis (Kolpin and
Martin, 2003), USGS uses a single sample to represent each well, generally the earliest sample
with complete data for the full suite of analytes.
NAWQA monitored bed sediment and fish tissue at sites considered likely to be
contaminated and sites that represent various land uses within each study unit. Most sites were
sampled once in each medium. In the case of sites sampled more than once, a single sample was
chosen to represent the site in the Pesticide National Synthesis analysis (Nowell, 2003). In the
case of multiple bed sediment samples, the earliest one with complete data for key analytes was
used to represent the site. In the case of multiple tissue samples, the earliest sample from the
first year of sampling that came from the most commonly sampled type offish in the study unit
was selected.
As part of the National Pesticide Synthesis, USGS also analyzed the occurrence of select
semivolatile organic compounds (SVOCs) in bed sediment at sites considered likely to be
contaminated and sites that represent various land uses within each study unit (Nowell and
Capel, 2003). Most sites were sampled only once. When multiple samples were taken, the
earliest one was used to represent the site in the analysis.
Fonofos January, 2008 4-2
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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
ground water, bed sediment, and tissue data analyses, the method of calculating concentration
percentiles sometimes varied depending on how much of the data was censored at particular
levels by the laboratory (i.e., because of the relatively large number of non-detections in these
media).
4.2.2 Results
Under the NAWQA program, USGS monitored fonofos between 1992 and 2001 in
representative watersheds and aquifers across the country. Reporting limits varied but did not
exceed 0.003 |ig/L. Results for surface water and ground water are presented in Tables 4-1 and
4-2. Fonofos was not monitored in bed sediment or biota.
Table 4-1 USGS National Synthesis Summary of NAWQA Monitoring of Fonofos in
Ambient Surface Water, 1992-2001
Land Use Type
Agricultural
Mixed
Undeveloped
Urban
No. of Samples
(and No. of
Sites)
1,889 (78)
1,020 (47)
60(4)
900 (33)
Detection
Frequency
3.05%
1.20%
0.00%
0.92%
50th Percentile
(Median)
Concentration
-------
Table 4-2 USGS National Synthesis Summary of NAWQA Monitoring of Fonofos in
Ambient Ground Water, 1992-2001
Land Use Type
Agricultural
Mixed (Major
Aquifer)
Undeveloped
Urban
No. of Wells
1,443
2,717
67
835
Detection
Frequency
0.07%
0.07%
0.0%
0.0%
50th Percentile
(Median)
Concentration
-------
value for health that is termed the Health Reference Level (HRL). Two different approaches
were used to derive the HRL, one for chemicals that cause cancer and exhibit a linear response to
dose and the other applies to noncarcinogens and carcinogens evaluated using a non-linear
approach.
The RfD for fonofos is 0.002 mg/kg/day based on plasma and blood cholinesterase
inhibition and signs of toxicity in a one-year dog feeding study (Hodge, 1995). Additional detail
concerning the RfD can be found in section 6.2. The Agency established the HRL for fonofos
using the RfD and a 20 percent relative source contribution as follows:
HRL = [(0.002 mg/kg/day x 70 kg)/2 L/day] x 20% = 0.014 mg/L (rounded to 0.010
mg/L or 10 |J-g/L)
4.3.3 Results
As a List 2 contaminant, fonofos was scheduled to be monitored by 300 public water
systems, including both large and small systems. These included the following systems in states
where fonofos use is particularly intensive: two systems in South Dakota; twelve systems in
North Carolina; and four systems in South Carolina. Data were received from 295 systems. The
data have been analyzed at the level of simple detections (at or above the minimum reporting
level, >MRL, or >0.5 |ig/L), exceedances of the health reference level (>HRL, or >10 |ig/L),
and exceedances of one-half the value of the HRL (^HRL, or >5 |ig/L).
Results of the analysis are presented in Tables 4-3 and 4-4. No detections of fonofos
were found in any samples, and thus there were also no exceedances of the HRL or one-half the
HRL.
Fonofos January, 2008 4-5
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Table 4-3 Summary UCMR1 Occurrence Statistics for Fonofos in Small Systems
Frequency Factors
Total Number of Samples
Percent of Samples with Detections
99' Percentile Concentration (all samples)
Health Reference Level (HRL)
Minimum Reporting Level (MRL)
Maximum Concentration of Detections
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 (GW & SW) with Detections (> MRL)
PWSs (GW & SW) > 1/2 HRL
PWSs (GW & SW) > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Population Served by PWSs > 1/2 HRL
Population Served by PWSs > HRL
UCMR Data -
Small Systems
643
0.00%
ViHRL, or PWSs > HRL = PWSs with at least one sampling result greater than or
equal to the MRL, exceeding the '/JHIRL benchmark, or exceeding the HRL benchmark, respectively; Population Served by
PWSs with detections, by PWSs >1/2HRL, or by PWSs >HRL = population served by PWSs with at least one sampling result
greater than or equal to the MRL, exceeding the 'AHRL 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.
-The HRL used in this analysis is a draft value since the registration for fonofos had been withdrawn.
Fonofos January, 2008
4-6
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Table 4-4 Summary UCMR1 Occurrence Statistics for Fonofos in 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 (GW & SW) with Detections (> MRL)
PWSs (GW & SW) > 1/2 HRL
PWSs (GW & SW) > HRL
Occurrence by Population Served
Population Served by PWSs with Detections
Population Served by PWSs > 1/2 HRL
Population Served by PWSs > HRL
UCMRData-
Large Systems
1,663
0.00%
!/2HRL, or PWSs > HRL = PWSs with at least one sampling result greater than or
equal to the MRL, exceeding the VzHRL benchmark, or exceeding the HRL benchmark, respectively; Population Served by
PWSs with detections, by PWSs >1/2HRL, or by PWSs >HRL = population served by PWSs with at least one sampling result
greater than or equal to the MRL, exceeding the 'ArTRL 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.
-The HRL used in this analysis is a draft value since the registration for fonofos has been withdrawn.
Fonofos January, 2008
4-7
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4.4 Summary
In ambient surface and ground water monitoring by USGS, the 95th percentile
concentrations in all land use settings were below the reporting limit. There were no detections
in undeveloped settings. In other settings, fonofos was detected more frequently in surface water
than in ground water (0.92% vs. 0% of urban samples; 3.05% vs. 0.07% of agriculture samples;
and 1.20% vs. 0.07% of samples from mixed land use settings).
For UCMR1, fonofos also was monitored by 295 public water systems. The data have
been analyzed at the level of simple detections (at or above the minimum reporting limit, >MRL,
or > 0.5 ng/L), exceedances of the HRL (>HRL, or >10 |ig/L), and exceedances of one-half the
value of the HRL (>/^HRL, or >5 |ig/L). No detections of fonofos were found in any samples,
and thus there were no exceedances of the HRL or one-half the HRL.
Fonofos January, 2008 4-8
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5.0 EXPOSURE FROM MEDIA OTHER THAN WATER
Fonofos registration was cancelled in 1999. Therefore, it is not considered as an
environmental contaminant of concern at the present time.
5.1 Exposure from Food
5.1.1 Concentration in Non-Fish Food Items
During the period when fonofos was used (before 1999), it was detected at a low
frequency in raw agricultural commodities and adult total diet samples (detection limit of 0.1
mg/kg) (Yess et al., 1991a,b; Schattenberg and Hsu, 1992; Minyard and Roberts, 1991). After
its cancellation, a mean value of 0.650 ppm of fonofos was detected in dry, roasted peanuts (n =
1) (U.S. FDA, 2003). Fonofos was detected, but not quantified, in domestic and imported food
samples analyzed in fiscal year 1994 (U.S. FDA, 1995). The compound was detected in 2 of 416
carrot samples at 2.0 and >2.0 ppm, respectively; 1 of 137 onion samples at 0.10 ppm; 1 of 769
potato samples at <0.05 ppm, analyzed as part of a Canadian fruit and vegetable commodity
survey of 21,982 samples conducted over a 27-month period from 1/1/92 to 3/31/94 (Neidert and
Saschenbrecker, 1996).
5.1.2 Concentrations in Fish and Shellfish
Analysis offish tissue for fonofos did not detect the chemical.
5.1.3 Intake of Fonofos from Food
Based on the information presented about, fonofos was not readily detected in food
items. Consequently, the typical average daily intake of fonofos from food for the general
population is anticipated to be close to zero.
5.2 Exposure from Air
5.2.1 Concentration of Fonofos in Air
Weekly composite air samples were collected from early April through to mid-September
1995 at three paired urban and agricultural sites along the Mississippi River region of the
Midwestern United States. The paired sampling sites were located in Mississippi, Iowa, and
Minnesota. A background site, removed from dense urban and agricultural areas, was located on
the shore of Lake Superior in Michigan. Two urban sites along the Mississippi River (Jackson,
Mississippi and Minneapolis, Minnesota), a rural area (Eagle Harbor, Lake Superior, Michigan),
and two agricultural areas (Rolling Fork, Mississippi and Princeton, Minnesota) were sampled
from early April to mid-September 1995. Fonofos was not detected in weekly composite
samples. A 3.75% detection frequency was reported for Iowa City, Iowa (Foreman et al., 2000).
Fonofos January, 2008 5-1
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5.2.2 Intake of Fonofos from Air
Based on the information presented about, fonofos was not readily detected in air.
Consequently, the typical average daily intake of fonofos from air for the general population is
anticipated to be close to zero.
5.3 Exposure from Soil
5.3.1 Concentration of Fonofos in Soil
Fonofos was used as a soil insecticide, which resulted in its direct release to the
environment. Fonofos was either not detected (detection limit 0.01 mg/kg) or concentrations
were up to 1.10 mg/kg in 28 farms of 6 vegetable growing areas in Southwestern Ontario in 1976
(Miles and Harris, 1978). The sediment of tailwater pits from irrigated corn and sorghum fields
in Kansas had a median range concentration of 4.0-48.4 |ig/kg with a maximum of 771 |ig/kg in
one pit (Kadoum and Mock, 1978). The loading and rinse areas of a farm chemical supply in
Iowa had a maximum concentration that exceeded 1000 |ig/kg in (Hallberg, 1989). In Illinois,
822 soil samples from 49 agrichemical facilities were analyzed. Fonofos was handled in 32
facilities, and 5 soil samples tested positive. Concentrations at four of the positive sites were: 96
jig/kg, median; 238 |ig/kg, mean; and 34-4,300 |ig/kg, range. Detection limits were 20-60 |ig/kg
(Krapac et al., 1995). Canadian agricultural soils had fonofos concentrations ranging from not
detected to 72 |ig/kg dry wt (Webber and Wang, 1995).
5.3.2 Intake of Fonofos from Soil
Human exposure to contaminants in soils is usually from dust that infiltrate homes,
automobiles etc. in the adult, and from dusts and incidental soil ingestion in children. Estimates
of intake for soil often assume an ingestion rate of 100 mg/day for children and 50 mg/day for
adults (U.S. EPA, 1996b). Using the data from Krapac et al. (1995) of 0.238 mg fonofos/kg soil
and the assumption that infants ingest 0.0001 kg/soil per day (100 mg), exposure of infants to
fonofos from soils would be about 24 ng/day. The value for adults would be about 12 ng/day.
0.238 mg/kg soil x 0.0001 kg soil = 0.0000238 mg/day (23.8 ng/day)
0.238 mg/kg soil x 0.00005 kg soil = 0.0000119 mg/day (11.9 ng/day)
5.4 Summary
Fonofos registration was cancelled in 1999, and it is not considered to be an
environmental contaminant of concern at the present time. Residues no longer are present in
agricultural produce. Levels once found in ambient air and soils have dissipated over time.
Fonofos January, 2008 5-2
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6.0 HAZARD AND DOSE-RESPONSE ASSESSMENT
6.1 Characterization of Hazard
6.1.1 Synthesis and Evaluation of Major Noncancer Effects
Fonofos is toxic in humans and animals. In humans, signs and symptoms of acute
intoxication by organophosphorus insecticides like fonofos include muscarinic, nicotinic, and
central nervous system (CNS) manifestations (HSDB, 2004). Such symptoms have been
documented in several case reports in which fonofos was accidentally ingested. In one reported
case of accidental ingestion, a 19-year-old woman who ate pancakes prepared with ingredients
containing fonofos (unknown dose level) developed nausea, vomiting, salivation, sweating, and
was found to have muscle fasciculation, blood pressure of 64/0 mm Hg, a pulse rate of 46,
pinpoint pupils, and profuse salivary and bronchial secretions. She also suffered a
cardiorespiratory arrest and developed a pancreatic pseudocyst. A second individual who also
ate the contaminated pancakes died (Hayes, 1982). Additionally, there was an outbreak of acute
food poisoning, in which nine individuals ate game-birds that showed the presence of nitrogen or
phosphorus atoms. This discovery was compatible with the pattern of fonofos toxicity and uses
on the hunting estate where the birds were located. The clinical picture showed: high level of
the creatine phosphokinase enzyme, general myalgias, vomiting or nausea and visual problems
(Gonzalez et al., 1996).
Acute oral toxicity studies in animals indicate that oral exposure to fonofos induces
clinical signs of toxicity that are typical of cholinesterase inhibitors. Such clinical signs include
depression, tremors, salivation, diarrhea, and labored breathing. Reported values for the oral
LD50 for female rats ranged from 3.2 to 7.9 mg/kg, while oral LD50 for male rats ranged from 6.8
to 18.5 mg/kg (Horton 1966a,b; Dean, 1977). Because fonofos is lipophilic, dermal exposure
also can result in toxic effects. Reported dermal LD50 values in rabbits ranged from 121 to 147
mg/kg (Horton 1966a,b). Reported dermal LD50 values in rabbits are 25 mg/kg for females and
100 mg/kg for males (Dean, 1977).
Organophosphates irreversibly bind to cholinesterase, causing the phosphorylation and
deactivation of acetylcholinesterase. The subsequent accumulation of acetylcholine at the neural
synapse causes an initial overstimulation, followed by eventual exhaustion and disruption of
postsynaptic neural transmission in the central nervous system and peripheral nervous system.
The neurotoxicity of fonofos has been questioned because it is an organophosphate pesticide.
Generally, fonofos has been shown to inhibit cholinesterase in hens, rats, and dogs;
consequently, studies have established no observed adverse effect levels (NOAELs) and lowest
observed adverse effect levels (LOAELs) based on this effect (Banerjee et al., 1968; Cockrell et
al., 1966; Hodge, 1995; Horner, 1993a,b; Miller, 1987; Miller et al., 1979; Pavkov and Taylor,
1988; Woodard et al., 1969).
Similar results of cholinesterase inhibition have been shown in chronic exposure studies.
Hodge (1995) conducted a study in which groups of 4 beagle dogs/sex/dose were administered
fonofos (94.6% a.i.) by capsule at dose levels of 0, 0.2, 1, or 1.75 mg/kg/day in corn oil for a
period of at least one year. The NOAEL was determined to be 0.2 mg/kg/day; however, this
NOAEL was considered to be a borderline NOAEL/LOAEL because there was minimal plasma
Fonofos January, 2008 6-1
-------
cholinesterase inhibition at 0.2 mg/kg/day which was generally weak and was not consistent.
The LOAEL, 1.0 mg/kg/day, was based on plasma and erythrocyte cholinesterase inhibition,
increases in alkaline phosphatase levels, clinical signs of toxicity, decreases in selected blood
chemistry values, increases in liver weights, and histologic changes in the ileum (Hodge, 1995).
(Note: There is a discrepancy in secondary source reporting of the middle dose. U.S. EPA
[2001] reports the dose as 0.4 mg/kg/day and California EPA [Cal EPA, 1998] reports it as 1
mg/kg/day. Both references identify the LOAEL as being 1 mg/kg/day, which, therefore, is
believed to be the true mid-dose.)
Woodard et al. (1969) also conducted a dog study, in which technical fonofos (99.5% and
99.8-99.9%) was administered via diet to male and female beagle dogs at 0, 16/8.0, 60 and 240
ppm (equivalent to 0, 0.4/0.2, 1.5, 6 mg/kg/day, respectively [Lehman, 1959]) for 2 years. After
14 weeks, the low dose was reduced from 16 ppm to 8 ppm. Four dogs/sex/dose were tested.
The cholinesterase NOAEL was 0.2 mg/kg/day, the cholinesterase LOAEL was 0.4 mg/kg/day,
the systemic NOAEL was 0.4/0.2 mg/kg/day, and the systemic LOAEL wasl.5 mg/kg/day.
However, there were major deficiencies with this study, which included an unusual feeding
pattern. There was no information on the frequency of diet preparation, storage, stability of the
test chemical in the diet, homogeneity of mixing, or concentration analyses. In the high-dose
group, a replacement dog was started 6 weeks into the study and did not appear to be kept an
extra 6 weeks at the other end of the study. Electrolytes were not measured for the clinical
chemistry analyses, the microscopic examinations were incomplete, and statistical calculations
were not conducted.
Technical fonofos (94%) was administered in the diet to groups of 50 Sprague Dawley
CD rats/sex/dose for 24 months at levels of 0, 4, 15, or 60 ppm and groups of 20/sex at 120 ppm
for 12 months. The mean compound intake (averaged across sexes) was approximately 0.17,
0.65, 2.6, and 6.6 mg/kg/day at 4, 15, 60, or 120 ppm, respectively. The systemic NOAEL was
determined to be 2.6 mg/kg/day and the LOAEL was 6.6 mg/kg/day based on decreases in body
weight and body weight gain (Pavkov and Taylor, 1988). In the same study, the NOAEL for
cholinesterase inhibition was 0.65 mg/kg/day and the LOAEL was 2.6 mg/kg/day based on
inhibition of cholinesterase activity (brain, serum and erythrocyte).
Other than cholinesterase inhibition, rats and dogs have shown decreases in body weights
and body weight gains after fonofos exposure in chronic exposure (Hodge, 1995; Pavkov and
Taylor, 1988; Woodard et al., 1969). Additionally, a common endpoint exhibited by dogs in
both studies was increased liver weights (Hodge, 1995; Woodard et al., 1969).
Two developmental studies with rabbits or mice were identified (Minor et al., 1982;
Pulsford, 1991; Sauerhoff, 1987). There were no developmental effects observed in rabbits that
were administered 0, 0.2, 0.5, or 1.5 mg/kg/day of technical fonofos (94% a.i.) via gavage
(Sauerhoff, 1987). Groups of 30 pregnant mice received 10 daily doses of technical fonofos
(95.6% a.i.) via gavage (Minor et al., 1982; Pulsford, 1991). The test article was administered in
corn oil at concentration of 0, 2, 4, 6, or 8 mg/kg/day from gestation days 6 through 15.
Developmental effects included an increase in the incidence of variant sternebrae ossifications at
dose levels of 6 mg/kg/day or greater. There also was a slight dilation of the fourth brain
ventricle observed in offspring in dose groups that received 4 mg/kg/day or greater. The
Fonofos January, 2008 6-2
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NOAEL for developmental effects in this study is 2 mg/kg/day, and the LOAEL is 4 mg/kg/day
based on the brain ventricle effect.
Only one reproductive study was identified, in which three generations of rats were
exposure to fonofos via diet at concentrations of 0, 10, or 31.6 ppm (equivalent to 0, 0.5, and
1.58 mg/kg/day, respectively, assuming that 1 ppm in the diet is equivalent to 0.05 mg/kg/day
[Lehman, 1959]) (Woodard et al., 1968). There were no treatment-related, adverse effects
observed at any dose level.
Fonofos did not exhibit mutagenic nor clastogenic characteristics in a bacterial reverse
mutation assay (Callander, 1990), chromosomal aberration test (James and Mackay, 1991), or in
vivo mouse micronucleus test (Jones and Mackay, 1990). Additionally, fonofos, with or without
metabolic activation, was not mutagenic in each of five microbial assay systems (the Ames
[Salmonella typhimurium] test; reverse mutation in Escherichia coli strain; mitotic
recombination in yeast, Saccharomyces cerevisiae D3; and differential toxicity assays in strains
of Escherichia coli and Bacillus subtilis) and in a test for unscheduled DNA synthesis in human
fibroblast (WI-38) cells (Simmon, 1979).
6.1.2 Synthesis and Evaluation of Carcinogenic Effects and Mode of Action
Currently, there is no evidence of carcinogenic potential in long term studies in rats
(Banerjee et al., 1968; Pavkov and Taylor, 1988) and mice (Sprague and Zwicker, 1987).
6.1.3 Weight of Evidence Evaluation for Carcinogenicity
Fonofos is classified as not likely to be carcinogenic to humans (U.S. EPA, 1998c,
2005a). This is because animal evidence failed to demonstrate a carcinogenic effect in at least
two well-designed and well-conducted studies in two appropriate animal species.
6.1.4 Potentially Sensitive Populations
The effect of concern for fonofos is cholinesterase (ChE) inhibition and the potential
aftermath on brain development in the young. There are no developmental neurotoxicity studies
with fonofos available at the present time. Children appear, however, potentially to be a
sensitive population based on developmental effects observed in studies with mice. Fonofos
treated groups had an increased incidence of variant ossifications of the sternebrae at dose levels
of 6 mg/kg/day or greater. Those exposed to 4 mg/kg/day or greater developed a slight dilation
of the fourth ventricle of the brain (Minor et al., 1982; Pulsford, 1991). Because the current RfD
for fonofos is based on an NOAEL of 0.2 mg/kg/day (Hodge, 1995), which is far below the
levels that caused developmental effects, this leads us to believe that children should be
adequately protected.
Fonofos January, 2008 6-3
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6.2 Reference Dose
6.2.1 Choice of Principle Study and Critical Effect
The principal study for determining the RfD is a chronic toxicity study, in which fonofos
(94.6% a.i.) was administered to groups of 4 beagle dogs/sex/dose by capsule at dose levels of 0,
0.2, 0.4 or 1.75 mg/kg/day in corn oil for a period of at least one year. Results showed that at 0.2
mg/kg/day, minimal sporadic plasma cholinesterase inhibition was observed in both sexes (7-
13%; 20% only once at 52 weeks in females). At 1.0 mg/kg/day, there were increases in alkaline
phosphatase levels (130-194% of control values). There also was inhibition of erythrocyte (51%
in males, 53% in females) and plasma cholinesterase (50% in both sexes) activities. At 1.75
mg/kg/day, there were clinical signs of toxicity in one animal, decreases in serum albumin and
total protein levels, increases in alkaline phosphatase levels (up to 217%), inhibition of
erythrocyte (62% in males, 63% in females), plasma (57% in males, 58% in females) and brain
(20% in females) cholinesterase activities and increases in absolute liver weights in males
(18.5%). Consequently, the NOAEL was 0.2 mg/kg/day and was considered to be a borderline
NOAEL/LOAEL because there was minimal plasma cholinesterase inhibition at 0.2 mg/kg/day
that was generally weak and inconsistent. The LOAEL, 1.0 mg/kg/day, was based on plasma
and erythrocyte cholinesterase inhibition and increases in alkaline phosphatase levels at 1.0
mg/kg/day and above, and clinical signs of toxicity, decreases in selected blood chemistry
values, increases in liver weights and histologic changes in the ileum at 1.75 mg/kg/day (Hodge,
1995).
6.2.2 Method of Analysis
The derivation of the reference dose (RfD) is described below. The RfD is an estimate
(with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human
population (including sensitive subgroups) that is likely to be without an appreciable risk of
deleterious effects during a lifetime. The RfD is derived from the NOAEL for the most sensitive
endpoint in the critical study, which is then divided by a variable uncertainty factor.
RfD = 0.2 mg/kg/dav = 0.002 mg/kg/day
100
where:
0.2 mg/kg/day = NOAEL derived from a one-year dog feeding study (Hodge, 1995),
based on plasma and erythrocyte cholinesterase inhibition, increases in alkaline
phosphatase levels, clinical and hematological toxicity, increased liver weight, and
histologic changes in the ileum.
100 = Uncertainty factor (UF), which includes a 10-fold UF for intraspecies variability,
and another 10-fold UF to account for interspecies extrapolation, as noted by NAS and
EPA.
Fonofos January, 2008 6-4
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As noted from the above equation, the RfD for fonofos is 0.002 mg/kg/day. The subsection
above describes the study used in support of this RfD.
6.3 Carcinogen Assessment
This section is not applicable because fonofos shows no evidence of carcinogenicity (as
described in Section 6.1.2, Synthesis and Evaluation of Carcinogenic Effects).
6.4 Sensitive Population Considerations
Because fonofos is a ChE inhibitor there is a concern about its potential to cause
neurodevelopmental effects. However, the Agency believes that the current RfD is adequately
protective of children. Because the current fonofos RfD of 0.002 mg/kg/day is based on an
NOAEL of 0.2 mg/kg/day and includes an additional uncertainty factor of 100, this RfD value is
1,000-fold below the NOAEL noted in the Woodward et al. (1986) developmental studies.
6.5 Post Re-registration Health Effects Publications
A literature search was conducted, and no studies were identified. All fonofos pesticide
uses have been cancelled.
6.6 CCL Health Reference Level
The CCL health reference level is 0.014 mg/L (0.01 mg/L when rounded to one
significant number). EPA derived the HRL using an RfD approach as follows: HRL = (RfD x70
kg)/2 L/day x RSC, where:
RfD = An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily
oral exposure (mg/kg/day) to the human population (including sensitive subgroups) that
is likely to be without an appreciable risk of deleterious effects during a lifetime. It can
be derived from an NOAEL, LOAEL, or BMD, with uncertainty factors generally
applied to reflect limitations of the data used;
70 kg = The assumed body weight of an adult;
2 L = The assumed daily water consumption of an adult;
RSC = The relative source contribution, or the level of exposure believed to result
from drinking water when compared to other sources (e.g., air), and is assumed to
be 20% unless noted otherwise.
Therefore, the HRL = 0.002 mg/kg/dav x 70kg x 0.20 = 0.014 mg/L
2L/day
A discussion of the HRL as a benchmark for evaluating occurrence using monitoring data from
public water systems is found in Section 4.3.2.
Fonofos January, 2008 6-5
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Fonofos January, 2008 6-6
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7.0 REGULATORY DETERMINATION AND CHARACTERIZATION OF RISK
FROM DRINKING WATER
7.1 Regulatory Determination for Chemicals on the CCL
The Safe Drinking Water Act (SDWA), as amended in 1996, required the Environmental
Protection Agency (EPA) to establish a list of contaminants to aid the Agency in regulatory
priority setting for the drinking water program. EPA published a draft of the first Contaminant
Candidate List (CCL) on October 6, 1997 (62 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, 1998d).
On July 18, 2003 EPA announced final Regulatory Determinations for one microbe and 8
chemicals (68 FR 42897) (U.S. EPA, 2003) after proposing those determinations on June 3, 2002
(67 FR 38222) (U.S. EPA, 2002b). The remaining 40 chemicals and ten microbial agents from
the first CCL became CCL 2 and were published in the Federal Register on April 2, 2004 (69 FR
17406) (U.S. EPA 2004) and finalized on February 24, 2005 (70FR:9071) (U.S. EPA, 2005b).
EPA proposed Regulatory Determinations for 11 chemicals from CCL2 on May 1, 2007
(72FR 24016) (U.S. EPA, 2007). Determinations for all 11 chemicals were negative based on a
lack of national occurrence at levels of health concern. The Agency is given the freedom to
determine that there is no need for a regulation if a chemical on the CCL fails to meet one of
three criteria established by the SDWA and described in section 7.1.1. After review of public
comments and submitted data the negative determinations for the 11 contaminants have been
retained. Each contaminant will be considered in the development of future CCLs if there are
changes in health effects and/or occurrence.
7.1.1 Criteria for Regulatory Determination
These are the three criteria used to determine whether or not to regulate a chemical on the
CCL:
The contaminant may have an adverse effect on the health of persons.
The contaminant is known to occur or there is a substantial likelihood that the
contaminant will occur in public water systems with a frequency and at levels of
public health concern.
In the sole judgment of the Administrator, regulation of such contaminant presents a
meaningful opportunity for health risk reduction for persons served by public water
systems.
The findings for all criteria are used in making a determination to regulate a contaminant.
As required by the SDWA, a decision to regulate commits the EPA to publication of a Maximum
Contaminant Level Goal (MCLG) and promulgation of a National Primary Drinking Water
Regulation (NPDWR) for that contaminant. The Agency may determine that there is no need for
a regulation when a contaminant fails to meet one of the criteria. A decision not to regulate is
Fonofos January, 2008 7-1
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considered a final Agency action and is subject to judicial review. The Agency can choose to
publish a Health Advisory (a nonregulatory action) or other guidance for any contaminant on the
CCL independent of the regulatory determination.
7.1.2 National Drinking Water Advisory Council Recommendations
In March 2000, the EPA convened a Working Group under the National Drinking Water
Advisory Council (NDWAC) to help develop an approach for making regulatory determinations.
The Working Group developed a protocol for analyzing and presenting the available scientific
data and recommended methods to identify and document the rationale supporting a regulatory
determination decision. The NDWAC Working Group report was presented to and accepted by
the entire NDWAC in July 2000.
Because of the intrinsic difference between microbial and chemical contaminants, the
Working Group developed separate but similar protocols for microorganisms and chemicals.
The approach for chemicals was based on an assessment of the impact of acute, chronic, and
lifetime exposures, as well as a risk assessment that includes evaluation of occurrence, fate, and
dose-response. The NDWAC protocol for chemicals is a semi-quantitative tool for addressing
each of the three CCL criteria. The NDWAC requested that the Agency use good judgment in
balancing the many factors that need to be considered in making a regulatory determination.
The EPA modified the semi-quantitative NDWAC suggestions for evaluating chemicals
against the regulatory determination criteria and applied them in decision-making. The
quantitative and qualitative factors for fonofos that were considered for each of the three criteria
are presented in the sections that follow.
7.2 Health Effects
The first criterion asks if the contaminant may have an adverse effect on the health of
persons. Because 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 estimate a dose at
which adverse health effects are either not likely to occur (threshold toxicant), or have a low
probability for occurrence (non-threshold toxicant). The key elements that must be considered
in evaluating the first criterion are the mode of action, the critical effect(s), the dose-response for
critical effect(s), the reference dose (RfD) for threshold effects, and the slope factor for
nonthreshold effects.
A full description of the health effects information and dose-response assessment
associated with exposure to fonofos is presented in Chapter 6 of this document and summarized
below in Section 7.2.2 and 7.2.3.
7.2.1 Health Criterion Conclusion
Fonofos (like many organophosphates) is toxic to humans and animals. Case reports
and acute oral toxicity studies in animals indicate that oral exposure to fonofos induces clinical
signs of toxicity that are typical of cholinesterase inhibitors. In humans, accidental exposure
Fonofos January, 2008 7-2
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included signs and symptoms of acute intoxication, nausea, vomiting, salivation, sweating,
muscle twitches, decreased blood pressure and pulse rate, pinpoint pupils, profuse salivary and
bronchial secretions, cardiorespiratory arrest and even death in one accidentally exposed
individual (Hayes, 1982; Gonzalez et al., 1996).
In animals, clinical signs of exposure include tremors, salivation, diarrhea, and labored
breathing (U.S. EPA, 2001). Subchronic and chronic exposure studies also indicate that oral
administration of fonofos inhibits cholinesterase (Banerjee et al., 1968; Cockrell et al., 1966;
Hodge, 1995; Horner, 1993b; Miller, 1987; Miller et al., 1979; Pavkov and Taylor, 1988;
Woodard et al., 1969). Cholinesterase inhibition is one of the critical effects associated with the
RfD, which was verified by EPA (1991) at 0.002 mg/kg/day. This RfD value was calculated
using an NOAEL of 0.2 mg/kg/day (Hodge, 1995) and divided by a 100-fold uncertainty factor
to account for inter- and intraspecies differences. The Agency derived an HRL for fonofos using
the RfD of 0.002 mg/kg/day and a 20 percent relative source contribution. The Agency derived
an HRL of 0.014 mg/L and rounded to 0.01 mg/L (or 10 |ig/L).
In accordance with the U.S. EPA 2005 Guidelines for Carcinogen Risk Assessment,
fonofos is classifiable as not likely to be carcinogenic to humans based on no evidence of
carcinogenic potential in long term studies in rats and mice (Banerjee et al. 1968; Pavkov and
Taylor, 1988; Sprague and Zwicker, 1987; U.S. EPA, 2005a). Fonofos is not mutagenic.
7.2.2 Hazard Characterization and Mode of Action Implications
Fonofos (like many organophosphates) is toxic to humans and animals. Case reports and
acute oral toxicity studies in animals indicate that oral exposure to fonofos induces clinical signs
of toxicity that are typical of cholinesterase inhibitors. Fonofos exposure through accidental
ingestion in humans results in signs and symptoms of acute intoxication by organophosphorus
insecticides including muscarinic, nicotinic, and central nervous system (CNS) manifestations
(HSDB, 2004). In acute oral toxicity studies, animals exhibited such clinical signs include
depression, tremors, salivation, diarrhea, and labored breathing.
Organophosphates irreversibly bind to cholinesterase, causing the phosphorylation and
deactivation of acetylcholinesterase. The subsequent accumulation of acetylcholine at the neural
synapse causes an initial overstimulation, followed by eventual exhaustion and disruption of
postsynaptic neural transmission in the central nervous system and peripheral nervous systems.
The neurotoxicity of fonofos has been questioned because it is an organophosphate pesticide.
Generally, fonofos has been shown to inhibit cholinesterase in hens, rats, and dogs;
consequently, studies have established NOAELs and LOAELs based on this effect (Banerjee et
al., 1968; Cockrell et al., 1966; Hodge, 1995; Horner, 1993b; Miller, 1987; Miller et al., 1979;
Pavkov and Taylor, 1988; Woodard et al., 1969).
7.2.3 Dose-Response Characterization and Implications in Risk Assessment
Cholinesterase inhibition is one of the critical effects associated with the RfD, which was
determined to be 0.002 mg/kg/day by EPA. This RfD value was calculated using an NOAEL of
0.2 mg/kg/day (Hodge, 1995), which was divided by a 100-fold uncertainty factor to account for
Fonofos January, 2008 7-3
-------
inter- and intraspecies differences. The HRL for fonofos is 0.014 mg/L and rounded to 0.01
mg/L (or 10 |ig/L) and was derived using the RfD (0.002 mg/kg/day) and a 20 percent relative
source contribution.
Fonofos is classified as not likely to be carcinogenic to humans because there is no
evidence of carcinogenic potential in the available long-term feeding studies in rats and mice
(Banerjee et al. 1968; Pavkov and Taylor, 1988; Sprague and Zwicker, 1987), and fonofos does
not appear to be mutagenic (Callander, 1990; James and Mackay, 1990; James and Mackay,
1991; Simmon, 1979).
EPA also evaluated whether health information is available regarding the potential
effects on children and other sensitive populations. Children appear potentially to be a sensitive
population based on developmental effects observed in studies with mice. Fonofos treated
groups had an increased incidence of variant ossifications of the sternebrae at dose levels of 6
mg/kg/day or greater. Those exposed to 4 mg/kg/day or greater developed a slight dilation of the
fourth ventricle of the brain (Minor et al., 1982; Pulsford, 1991). Because the current RfD for
fonofos is based on an NOAEL of 0.2 mg/kg/day (Hodge, 1995), which is far below the levels
that caused developmental effects, this leads us to believe that children should be adequately
protected.
7.3 Occurrence in Public Water Systems
The second criterion for regulating a chemical on the CCL asks if the contaminant is
known to occur or if there is a substantial likelihood that the contaminant will occur in public
water systems with a frequency and at levels of public health concern. In order to address this
question the following information was considered:
Monitoring data from public water systems
Ambient water concentrations and releases to the environment
Environmental fate
Data on the occurrence of fonofos 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 fonofos, as well those that reported concentrations of fonofos
above an estimated drinking-water FIRL. For noncarcinogens, the estimated HRL level was
calculated from the RfD assuming that 20% of the total exposure would come from drinking.
For carcinogens, the HRL was the 10"6 risk level (i.e, the probability of 1 excess tumor in a
population of a million people). The HRLs are benchmark values that were used in evaluating
the occurrence data while the risk assessments for the contaminants were being developed.
The available monitoring data, including indications of whether or not the contaminant is
a national or a regional problem, are included in Chapter 4 of this document and summarized
below. Additional information on production, use, and fate are found in Chapters 2 and 3.
Fonofos January, 2008 7-4
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7.3.1 Occurrence Criterion Conclusion
The available data for fonofos production, use and environmental releases all show a
downward trend. This is because cancellation of the pesticide was announced in the Federal
Register on May 6, 1998 (63 FR 25033), with an effective date of November 2, 1998 plus a one-
year grace period to permit the exhaustion of existing stocks (U.S. EPA, 1999a). Consequently,
the National Center for Food and Agricultural Policy (NCFAP) estimated that 3.2 million pounds
of active ingredient were applied annually to 24 types of crops on 2.6 million acres in 1992, as
compared to approximately 0.4 million pounds of active ingredient being applied annually to 19
types of crops on 0.3 million acres in 1997 (NCFAP, 2004). Additionally, there were no
detections of fonofos found in any of the 300 public water systems sampled.
Based on the occurrence data, it is unlikely that fonofos will occur in public water
systems at frequencies or concentration levels that are of public health concern. Thus, the
evaluation for the second criterion is negative. Cancellation of the pesticide was announced in
the Federal Register on May 6, 1998 (63 FR 25033), with an effective date of November 2, 1998
plus a one-year grace period to permit the exhaustion of existing stocks (U.S. EPA, 1999a).
7.3.2 Monitoring Data
Under the National Water-Quality Assessment (NAWQA) program, US Geological
Survey (USGS) monitored fonofos between 1992 and 2001 in representative watersheds and
aquifers across the country. Reporting limits varied but did not exceed 0.003 |ig/L. In surface
water, fonofos was detected at frequencies ranging from 0.0% of the samples from undeveloped
land settings to 0.92% in urban land use settings, 1.20% in mixed land use settings, and 3.05% in
agricultural land use settings. The 95th percentile concentrations in all land use settings were
below the reporting limit. The highest maximum concentration, estimated at 1.20 |ig/L,
occurred in an agricultural land use setting (Martin et al., 2003).
In ground water, fonofos detection frequencies ranged from 0.0% of the samples from
urban and undeveloped settings to 0.07% in agricultural and mixed land use (major aquifer)
settings. The 95th percentile concentrations were less than the reporting limit in all settings. The
highest concentration, 0.009 |ig/L, occurred in an agricultural setting (Kolpin and Martin, 2003).
Additionally, the first Unregulated Contaminant Monitoring Regulation (UCMR1)
collected information on the national occurrence of select emerging contaminants in drinking
water. There were 2 components to the monitoring. The first monitoring component,
Assessment Monitoring, was for the UCMR1 contaminants with well-developed analytical
methods ("List 1" contaminants). The second component of the UCMR1, the Screening Survey
was for those contaminants with analytical methods that may need to be further refined for use in
a large national survey ("List 2" contaminants) (U.S. EPA, 2001). Fonofos was a "List 2"
contaminant; consequently, the Screening Survey was designed to be conducted by a total of 300
public water systems (120 large and 180 small systems). List 2 monitoring was conducted
between 2001 and 2003.
Fonofos January, 2008 7-5
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Data were reported from 295 systems. There were no detections of fonofos in any
samples when the data were analyzed at the level of simple detections (> minimum reporting
limit MRL, or >0.5 |ig/L), at the level of exceedances of the HRL (>HRL, or >10 |ig/L), and at
the level of exceedances of one-half the value of the HRL (>/^HRL, or >5 |ig/L).
7.3.3 Use and Fate Data
Fonofos was used as a soil insecticide (Spencer, 1982; Tomlin, 2002, U.S. EPA, 1999a),
and in recent years, the chemical was predominantly used on agricultural crops. Cancellation of
the pesticide was announced in the Federal Register on May 6, 1998 (63 FR 25033), with an
effective date of November 2, 1998 plus a one-year grace period to permit the exhaustion of
existing stocks.
Monitoring data from public water systems are supportive of a decline in the presence of
fonofos in the water. In fact, there were no detections of fonofos found in any of the 295 public
water systems reporting data. Fonofos is strongly sorptive in soil and insoluble in water;
therefore it is more likely to remain in soil overtime.
7.4 Risk Reduction
The third criterion asks if, in the sole judgment of the Administrator, regulation presents
a meaningful opportunity for health risk reduction for persons served by public water systems.
In evaluating this criterion, EPA looked at the total exposed population, as well as the population
exposed to levels above the estimated HRL (0.01 mg/L). Estimates of the populations exposed
and the levels to which they are exposed were derived from the monitoring results. These
estimates are included in Chapter 4 of this document and summarized in section 7.4.2 below.
In order to evaluate risk from exposure through drinking water, EPA considered the net
environmental exposure from all potential sources/media in comparison to the exposure from
drinking water. For example, if exposure to a contaminant occurs primarily through ambient air,
regulation of emissions to air provides a more meaningful opportunity for EPA to reduce risk
than does regulation of the contaminant in drinking water. In making the regulatory
determination, the available information on exposure through drinking water (Chapter 4) and
information on exposure through other media (Chapter 5) were used to estimate the fraction that
drinking water contributes to the total exposure. The EPA findings are discussed in Section
7.4.3 below.
In making its regulatory determination, EPA also evaluated effects on potentially
sensitive populations, including the fetus, infants and children. Sensitive population
considerations are included in section 7.4.4.
7.4.1 Risk Criterion Conclusion
The presence of fonofos in water is rare. There were no detections of fonofos in any
samples when the data were analyzed at the level of simple detections (>MRL or >0.5 |ig/L), at
the level of exceedances of the HRL (>HRL or >10 |ig/L), and at the level of exceedances of
Fonofos January, 2008 7-6
-------
one-half the value of the HRL (>/^HRL, or >5 |ig/L). On the basis of these observations, the
impact of regulating fonofos concentrations in drinking water on health risk reduction is likely to
be small. Thus, the outcome of the evaluation of the third criterion is negative.
7.4.2 Exposed Population Estimates
Fonofos was scheduled to be monitored by 300 public water systems. There were no
detections of fonofos found in any of the samples. Therefore, it appears that the general
population is not exposed to fonofos through drinking water consumption or use.
7.4.3 Relative Source Contribution
Relative source contribution analysis compares the magnitude of exposure expected via
drinking water to the magnitude of exposure from intake of fonofos in other media, such as food,
air, and soil. In situations where fonofos occurs in drinking water, the water is likely to be the
major source of exposure. Intake values found in food, air, and soil are very low but the
available data are not complete, and therefore, the RSC value should remain the default value of
20% if a lifetime HA were to be developed for noncancer effects.
7.4.4 Sensitive Populations
Children appear potentially to be the most sensitive population based on developmental
effects observed in studies with mice. Fonofos treated groups had an increased incidence of
variant ossifications of the sternebrae at dose levels of 6 mg/kg/day or greater. Those exposed to
4 mg/kg/day or greater developed a slight dilation of the fourth ventricle of the brain (Minor et
al., 1982; Pulsford, 1991). Because the current RfD is based on an NOAEL of 0.2 mg/kg/day
(Hodge, 1995), children should be adequately protected. This is because the determined
NOAEL from the Hodge study is far below the NOAELs available from the developmental and
reproductive studies for fonofos.
7.5 Regulatory Determination Decision
As stated in Section 7.1.1, a positive finding for all three criteria is required in order to
make a determination to regulate a contaminant. In the case of fonofos, only the finding for the
criterion on health effects is positive. Fonofos may have an adverse effect on the health of
persons. To date, there have been no detections of fonofos found in any of the samples. Because
use of this pesticide was cancelled, it is unlikely that it will be found in water supplies in the
future. Therefore, it appears that the general population is not exposed to fonofos through
water consumption or use. On the basis of these observations, the impact of regulating fonofos
concentrations in drinking water on health risk reduction is likely to be small. Regulation of
fonofos in public water systems does not appear to present a meaningful opportunity for health
risk reduction.
Fonofos January, 2008 7-7
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Fonofos January, 2008 7-8
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APPENDIX A: Abbreviations and Acronyms
a.i. active ingredient
atm atmosphere
BCF bioaccumulation factor
Cal EPA California EPA
CAS Chemical Abstracts Registry
CCL Contaminant Candidate List
ChE cholinesterase
cm centimeter
CNS central nervous system
CWS community water system
EPA Environmental Protection Agency
FR Federal Register
Hg mercury
FIRL health reference level
HSDB Hazardous Substances Database
Kads adsorption coefficient
kg kilogram
K organic carbon partitioning coefficient
L liter
LOAEL lowest observed adverse effect level
m meter
MCLG Maximum Contaminant Level Goal
mg milligram
mL milliliter
mm millimeter
MRL minimum reporting level
NAWQA National Water Quality Assessment
NCFAP National Center for Food and Agricultural Policy
NCOD National Drinking Water Contaminant Occurrence Database
NOW AC National Drinking Water Advisory Council
NOAEL no observed adverse effect level
NPDWR National Primary Drinking Water Regulation
NTNCWS non-transient non-community water system
OPP Office of Pesticides Programs
ppm parts per million
PWS Public Water Systems
QAPP Quality Assurance Proj ect Plan
RED Re-registration Eligibility Document
RfD reference dose
RL reporting limit
RSC relative source contribution
SDWA Safe Drinking Water Act
SVOCs select semivolatile organic compounds
UCMR1 Unregulated Contaminant Monitoring Regulation 1
Fonofos January, 2008
Appendix A-l
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UF uncertainty factor
|J,g microgram
USDA United States Department of Agriculture
U.S. EPA United States Environmental Protection Agency
U.S. FDA United States Food and Drug Administration
USGS United States Geological Service
VOC volatile organic compound
Fonofos January, 2008 Appendix A-2
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