Provisional Peer Reviewed Toxicity Values for Dinoseb (CASRN 88-85-7)


United States
Environmental Protection
1=1 m m Agency
EPA/690/R-02/005F
Final
5-31-2002
Provisional Peer Reviewed Toxicity Values for
Dinoseb
(CASRN 88-85-7)
Derivation of an Oral Slope Factor
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
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NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(.imol
micromoles
voc
volatile organic compound
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5-31-2002
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
DINOSEB (CASRN 88-85-7)
Derivation of an Oral Slope Factor
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1. EPA's Integrated Risk Information System (IRIS).
2. Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3. Other (peer-reviewed) toxicity values, including:
~ Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~ California Environmental Protection Agency (CalEPA) values, and
~ EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
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Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
Dinoseb is classified on IRIS in cancer weight-of-evidence Group D - not classifiable as
to human carcinogenicity (U.S. EPA, 2001). The assessment, verified on 5/3/89, was based on
lack of human and inadequate animal carcinogenicity data, comprising two studies in mice (Innes
et al., 1969; Dow Chemical Co., 1981) and one in rats (Dow Chemical Co., 1977). Dinoseb is
also listed in Group D on the Drinking Water Standards and Health Advisories list (U.S. EPA,
2000). A cancer assessment for dinoseb is not included in the HEAST (U.S. EPA, 1997). The
CARA list (U.S. EPA, 1991, 1994) includes a Health and Environmental Effects Profile (HEEP)
for Dinoseb (U.S. EPA, 1984) that found no evidence for carcinogenicity of this chemical. IARC
(2001) has not reviewed the carcinogenicity of dinoseb. ATSDR (2001) has not produced a
Toxicological Profile for dinoseb and no Environmental Health Criteria Document is available
(WHO, 2001). NTP (2001) has not studied the carcinogenic potential of dinoseb. Updated
literature searches for cancer data were conducted from 1983 to 2001. The databases searched
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5-31-2002
were: TOXLINE, MEDLINE, CANCERLIT, CCRIS, TSCATS, HSDB, RTECS, GENETOX,
DART/ETICBACK, and EMIC/EMICBACK.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
Case-control studies in Swedish cancer patients, described in U.S. EPA (1984), found no
evidence of increased risk of malignant lymphomas or malignant mesenchymal soft tissue tumors
associated with dinoseb exposure (Eriksson et al., 1979; Hardell et al., 1981).
Animal Studies
Long-term studies of dinoseb exposure in mice (Innes et al., 1969; Dow Chemical Co.,
1981) and rats (Dow Chemical Co., 1977) did not show an increase in tumors and/or were
inadequate studies of carcinogenicity (U.S. EPA, 1984, 2001). No additional studies subsequent
to the 1989 IRIS review were located.
Other Studies
Genotoxicity assays of dinoseb have generally shown no mutagenic activity, but have
demonstrated an ability to interact with DNA and RNA (U.S. EPA, 1984, 2001). In bacteria,
dinoseb was not mutagenic in multiple assays in Salmonella typhimurium and Escherichia coli,
but produced positive results in differential toxicity tests comparing growth of repair-
/recombination-deficient and proficient strains of S. typhimurium, E. coli and Bacillus subtilis.
Assays for mitotic gene conversion in the yeast Saccharomyces cerevisiae produced mixed
results. A sex-linked recessive lethality assay in Drosophila was negative. Results were also
negative for unscheduled DNA synthesis in cultured human lung fibroblasts. Sperm morphology
studies showed an increase in the occurrence of abnormal sperm in treated rats, but no effect in
mice.
FEASIBILITY OF DERIVING A PROVISIONAL ORAL SLOPE FACTOR FOR
DINOSEB
A provisional oral slope factor for dinoseb cannot be derived due to lack of human and
inadequate animal cancer data.
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REFERENCES
ATSDR (Agency for Toxicological Substances Disease Registry). 2001. Internet HazDat
Toxicological Profile Query. U.S. Department of Health and Human Services, Public Health
Service. Atlanta, GA. Examined October 10, 2001. Online.
http://www.atsdr.cdc.gov/gsql/toxprof.script
Dow Chemical Company. 1977. Available from EPA. Write to FOI, EPA, Washington, DC
20460. (Cited in U.S. EPA, 2001)
Dow Chemical Company. 1981. Available from EPA. Write to FOI, EPA, Washington, DC
20460. (Cited in U.S. EPA, 2001)
Eriksson, M., N.O. Berg, L. Hardell et al. 1979. Case control study of malignant mesenchymal
soft-tissue tumors and exposure to chemical substances. Lakartidningen. (Swe.) 76(4): 3872-
3875. (Cited in U.S. EPA, 1984)
Hardell, L., M. Eriksson., P. Lenner et al. 1981. Malignant lymphoma and exposure to
chemicals, especially organic solvents, chlorophenols, and phenoxy acids: A case controlled
study. Br. J. Cancer. 43:169-176. (Cited in U.S. EPA, 1984)
IARC (International Agency for Research on Cancer). 2001. Cumulative Cross Index to IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC Monographs.
Examined October 10, 2001. Online.
http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
Innes, J.R.M., M.G. Valerio, L. Petruceli et al. 1969. Bioassay of pesticides and industrial
chemicals for tumorigenicity in mice. A preliminary note. J. Natl. Cancer Inst. 42: 1104-1114.
(Cited in U.S. EPA, 1984, 2001)
NTP (National Toxicology Program). 2001. Management Status Report. Examined October 10,
2001. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ALL SRCH/iH ALL SRCH Frames.html
U.S. EPA. 1984. Health and Environmental Effects Profile for Dinoseb. Prepared by the Office
of Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste, Washington, DC.
U.S. EPA. 1989. Notes of the 6/13/89 CRAVE Work Group Meeting (summary sheet dated
5/5/89). Available from: National Center for Environmental Assessment, Washington, DC.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
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U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC.
EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2000. Drinking Water Standards and Health Advisories. Summer 2000. Office of
Water, Washington, DC. Online, http://www.epa.gov/ost/drinking/standards/
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
October 10, 2001. Online, http://www.epa.gov/iris/
WHO (World Health Organization). 2001. World Health Criterial Publications catalogue.
Examined October 10, 2001. Online, http://www.who.int/dsa/cat98Zzehc.htm
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