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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEOs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained from Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for In this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document Is sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval, for example, one that does
not constitute a significant portion of the Hfespan. This type of exposure
estimate has not been extensively used, or rigorously defined as previous
risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs Is the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfDs are not estimated. A
carcinogenic potency factor, or q-|* (U.S. EPA, 1980), 1s provided Instead.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxldty and cardno-
genlclty are derived. The RQ Is used to determine the quantity of a hazar-
dous substance for which notification 1s required 1n the event of a release
as specified under the CERCLA. These two RQs (chronic toxldty and cardno-
genlclty) represent two of six scores developed (the remaining four reflect
tgnltabllUy, reactivity, aquatic toxldty, and acute mammalian toxldty).
Chemical-specific RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxldty and cancer-based RQs are defined 1n U.S.
EPA, 1984 and 1986a, respectively.
111
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EXECUTIVE SUMMARY
Furan 1s a colorless, low-boiling and highly flammable liquid at room
temperature, with a strong ethereal odor (McKllUp and Sherman, 1980).
Unless stabilized, 1t will react slowly with air to form an unstable,
explosion-prone peroxide {Ounlop, 1966). It Is mlsdble with most common
organic solvents (McKllUp and Sherman, 1980) and the solubility 1n water 1s
10 g/SL at 25°C (Dunlop, 1966). Furan Is produced commercially by
decarbonylatlon of furfural (McKllUp and Sherman, 1980). QO Chemicals,
Inc., Memphis, TN, 1s the only domestic manufacturer of this compound (SRI,
1986; USITC, 1986). Production volume data could not be located 1n the
available literature as cited 1n Appendix A. Furan Is used as an
Intermediate In the production of other Industrial chemicals, especially
pyrrole, tetrahydrofuran and thlophene; for use as Pharmaceuticals,
herbicides and various polymers (Hawley, 1981; McKllUp and Sherman, 1980).
If released to the atmosphere, furan Is expected to exist almost
entirely 1n the vapor phase. Reaction with photochemlcally generated
hydroxyl radicals Is predicted to be the primary removal mechanism during
daylight (half-life, 2-6 hours) and reaction with nitrate radicals Is
predicted to be the primary removal mechanism (half-life, -1/2 hour) during
nighttime. Removal from the atmosphere by reaction with ozone or physical
processes 1s expected to be relatively Insignificant. If furan Is released
to water, volatilization Is expected to be an Important, If not the
dominant, removal mechanism. The volatilization half-life of furan 1n a
typical river 1 m deep, flowing 1 m/sec, with a wind speed of 3 m/sec was
estimated to be 2.5 hours (see Section 2.2.4.). Chemical hydrolysis,
bloaccumulatlon 1n aquatic organisms and physical adsorption to suspended
solid or sediments are not expected to be Important fate processes. If
1v
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released to moist soil, furan may be susceptible to rapid volatilization.
In the absence of significant blotlc or abiotic processes, residual furan 1n
moist soils Is susceptible to significant leaching to groundwater. If
released to dry soil, furan may volatilize rapidly.
The most probable route of human exposure to furan 1s by Inhalation.
Infants may be exposed to this compound by Ingestlon of mother's milk, since
furan had been detected 1n 1 of 12 samples of mother's milk (PelUzzaM et
al., 1982). Furan has also been Identified as a volatile component of
roasted filberts (K1nl1n et al., 1972). Furan has been Identified as a
gas-phase component of cigarette smoke (Sakuma et al., 1975), wood smoke
(Klelndlenst et al., 1986), exhaust gas from delsel and gasoline engines
(Hampton et al., 1982) and volatile emissions from sorb trees (Isldorov et
al., 1985). Furan was detected 1n the expired air of two out of three male
smokers and four out of five male nonsmokers from Brooks Air Force Base,
TX. The rate of furan expiration ranged between 0.25-98 for smokers and
0.33-28 yg/hr for nonsmokers (Conkle et al., 1975). This compound has
also been detected In the expired air from male and female nonsmokers from
Chicago, IL (Krotoszynskl et al., 1979). This compound has been qualita-
tively Identified 1n the Niagara River and two creeks 1n the Niagara River
watershed (Elder et al., 1981; Great Lakes Water Quality Board. 1983).
Little Information was available concerning toxldty of furan to aquatic
biota. Velth et al. (1983) reported a 96-hour LC5Q of 61 mg/8, for
fathead minnows. Call et al. (1985) calculated an HATC of 10.0 mg/8, based
on a NOEC of 8.27 mg/l and a LOEC of 12.2 mg/4. from a 31-33 day
continuous flow bloassays with early life stages of fathead minnows.
Information regarding the pharmacoklhetlcs of furan was limited. The
available data Indicate that furan 1s absorbed extensively by the Inhalation
route (Egle and Gochberg, 1979) and was distributed to the lungs, kidney and
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liver following IntraperHoneal Injection (Gammal et a!., 1984; Wiley et
al., 1984). Metabolic activation may be required for furan Induced toxlclty
(Hasuda et al., 1984).
Dose-related toxic hepatitis was reported In both sexes of F-344 rats
and B6C3F1 mice when furan was administered by gavage for 13 weeks (SRI,
1982a,b). The liver lesions were considered minimal 1n low-dose rats and
did not occur In the two lowest dose groups of male and female mice.
High-dose male and female rats and high-dose male mice had reduced body
weight gains. Dose-related Increase In liver weight was reported 1n all
treated rats except low-dose females and 1n male and female mice at the two
highest dose levels.
Pertinent data regarding the cardnogenlclty, teratogenlclty or other
reproductive effects of furan could not be located 1n the available litera-
ture as cited 1n Appendix A. Furan was reported to be nonmutagenlc when
tested In the presence and absence of S-9 In assays with Salmonella typhl-
murlum and Euglena gracllls (Hortelmans et al., 1986; EbMnge et al., 1979).
Furan was clastogenlc to Chinese hamster ovary cells when cultured In the
presence of S-9 (Stlch et al., 1981).
. A subchronlc RfD for oral exposure of 1 mg/day was based on the NOAEL of
2 mg/kg for mice In the 13-week gavage study (SRI, 1982b). Application of
an additional uncertainty factor yielded an RfD of 0.1 mg/day for chronic
oral exposure. An RQ of 100 for furan was based on the occurrence of severe
liver lesions In male mice In the same study (SRI, 1982b).
v1
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TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 2
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. AIR 4
2.1.1. Reaction with Hydroxyl Radicals 4
2.1.2. Reaction with Ozone 4
2.1.3. Reaction with Nitrate Radicals 4
2.1.4. Physical Removal Processes 4
2.2. WATER 5
2.2.1. Hydrolysis 5
2.2.2. B1oaccumulat1on 5
2.2.3. Adsorption 5
2.2.4. Volatilization 6
2.2.5. B1odegradat1on 6
2.3. SOIL 6
2.3.1. Leaching 6
2.3.2. Volatilization 6
2.4. SUMMARY 7
3. EXPOSURE 8
3.1. WATER 8
3.2. FOOD 8
3.3. INHALATION 8
3.4. DERMAL 9
3.5. SUMMARY 9
4. AQUATIC TOXICITY 11
4.1. ACUTE TOXICITY 11
4.2. CHRONIC EFFECTS 11
4.3. PLANT EFFECTS 11
4.4. SUMMARY 11
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TABLE OF CONTENTS (cont.)
PHARMACOKINETCS
5.1. ABSORPTION ........................ 12
5.2. DISTRIBUTION ....................... 12
5.3. METABOLISM ........................ 13
5.4. EXCRETION ......................... 13
5.5. SUMMARY ..... . .................... 13
6. EFFECTS ............................. 15
6.1. SYSTEMIC TOXICITY ............. ........ 15
6.1.1. Inhalation Exposures ............... 15
6.1.2. Oral Exposures .................. 15
6.1.3. Other Relevant Information ............ 16
6.2. CARCINOGENICITY ...................... 16
6.2.1. Inhalation and Oral ............... 16
6.2.2. Other Relevant Information ............ 17
6.3. MUTAGENICITY ....................... 17
6.4. TERATOGENICITY ...................... 17
6.5. OTHER REPRODUCTIVE EFFECTS ................ 17
6.6. SUMMARY .......................... 17
7. EXISTING GUIDELINES AND STANDARDS ................ 19
7.1. HUMAN ........................... 19
7.2. AQUATIC .......................... 19
8. RISK ASSESSMENT ......................... 20
8.1. CARCINOGENICITY ............. . . ....... 20
8.1.1. Weight of Evidence ................ 20
8.1.2. Quantitative Risk Estimates ........... 20
8.2. SYSTEMIC TOXICITY ..................... 20
8.2.1. Inhalation Exposure ............... 20
8.2.2. Oral Exposure .................. 20
9. REPORTABLE QUANTITIES ...................... 23
9.1. BASED ON SYSTEMIC TOXICITY . . .............. 23
9.2. BASED ON CARCINOGENICITY ................. 23
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TABLE OF CONTENTS (cont.)
10. REFERENCES.
APPENDIX A: LITERATURE SEARCHED 35
APPENDIX B: SUMMARY TABLE FOR FURAN 38
1x
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LIST OF ABBREVIATIONS
BCF Bloconcentratlon factor
CAS Chemical Abstract Service
CS Composite score
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow Octanol/water partition coefficient
LOEC Lowest-observed-effect concentration
MATC Maximum acceptable toxicant concentration
MED Minimum effective dose
NOAEL No-observed-adverse-effect level
NOEC No-observed-effect concentration
ppb Parts per billion
RfD Reference dose
RQ Reportable quantity
RV(j Dose-rating value
RVe Effect-rating value
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Furan 1s also known as furfuran, oxole, dlvlnylene oxide and tetrole
(Wlndholz, 1983). The structure, molecular weight, empirical formula and
CAS Registry number for this compound are as follows:
Molecular weight: 68.08
Empirical formula: C.H.O
CAS Registry number: 110-00-9
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Furan 1s a flammable, colorless liquid at room temperature with a
strong, ethereal odor {McKlllIp and Sherman, 1980). Although It will turn
brown while standing In air, the addition of a small amount of water will
retard color change (Hawley, 1981). Unless stabilized, furan will react
slowly with air to form an unstable, explosion-prone peroxide (Dunlop,
1966). Butylated hydroxytoluene (BHT) 1s added to Inhibit this reaction
(Verschueren, 1983). Furan Is mlsdble with most common organic solvents
Including ethyl acetate, methanol, ethanol, acetone, toluene, petroleum
ether and chloroform {McKHHp and Sherman, 1980; Dunlop, 1966). Pertinent
physical properties are as follows:
Melting point, °C: -85.6 R1dd1ck et al., 1986
Boiling point, °C: 31.4 Rlddlck et al., 1986
Vapor pressure at 25°C: 600 mm Hg Boubllk et al., 1984
Water solubility at 25°C: 1.01x10* mg/a Valvanl et al., 1981
Log Kow: 1.34 Hansch and Leo, 1985
Specific gravity, 20/4°C: 0.9378 Rlddlck et al., 1986
20
Refractive Index, njju: 1.4214 Rlddlck et al., 1986
0067d -1- 10/02/87
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Flashpoint, °C: -36 (closed cup) R1dd1ck et al., 1986
Furan undergoes substitution and addition reactions under controlled
conditions (McK1ll1p and Sherman, 1980). Furan 1s hydrolyzed by aqueous
adds, and this reaction 1s accompanied by res1n1f1cat1on (U.S. EPA, 1986b).
1.3. PRODUCTION DATA
Furan 1s produced commercially by decarbonylatlon of furfural (HcKlllIp
and Sherman, 1980). QO Chemicals, Inc., Memphis, TN, 1s the only domestic
manufacturer of this compound (SRI, 1986; USITC, 1986). Production volume
data could not be located In the available literature as cited 1n Appendix A.
1.4. USE DATA
Furan 1s used as an Intermediate 1n the production of other Industrial
chemicals, especially pyrrole, tetrahydrofuran and thlophene (Hawley, 1981;
McK1ll1p and Sherman, 1980). It Is also used as an Intermediate 1n the
production of Pharmaceuticals, herbicides, stabilizers and various polymers
(McKllUp and Sherman, 1980).
1.5. SUMMARY
Furan Is a colorless, flammable liquid at room temperature, with a
strong ethereal odor (McKHlIp and Sherman, 1980). Unless stabilized with
BHT, 1t will react slowly with air to form an unstable, explosion-prone
peroxide (Duniop, 1966). It 1s mlsdble with most common organic solvents
and 1s slightly soluble 1n water (McKllUp and Sherman, 1980). Furan 1s
produced commercially by decarbonylatlon of furfural (McKllUp and Sherman,
1980). QO Chemicals, Inc., Memphis, TN, 1s the only domestic manufacturer
of this compound (SRI. 1986; USITC, 1986). Production volume data could not
be located In the available literature as cited 1n Appendix A. Furan Is
used as an Intermediate In the production of other Industrial chemicals;
0067d -2- 10/02/87
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especially pyrrole, tetrahydrofuran and thlophene; for use as
Pharmaceuticals, herbicides and various polymers (Hawley, 1981; McKlllIp and
Sherman, 1980).
0067d -3- 09/25/87
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2. ENVIRONMENTAL FATE AND TRANSPORT
Pertinent data regarding the environmental fate and transport of furan
are limited. When possible, Information concerning fate and transport of
this compound were derived from physical property data or molecular
structure.
2.1. AIR
Because of Us relatively high vapor pressure of 600 mm Hg at 25°C
(Boubllk et al., 1984), furan Is expected to exist almost entirely In the
vapor phase In the atmosphere (Elsenrelch et al., 1981).
2.1.1. Reaction wHh Hydroxyl Radicals. The half-life for the reaction
of furan with photochemically generated hydroxyl radicals at 22°C has been
calculated to be 6.0 and 2.3 hours, using experimentally derived rate
constants of 4.0X10"11 and 1.05xlO~10 cm3/molecule-sec (Atkinson,
1985; Lee and Tang, 1982), respectively, and an average atmospheric hydroxyl
radical concentration of 8.0xl05 molecules/cm3 (U.S. EPA, 1987)
2.1.2. Reaction with Ozone. The half-life for furan reaction with ozone
In the atmosphere was estimated to be 3.3 days, using an experimentally
derived reaction rate constant of 2.4xlO~18 cm3/molecule-sec at room
temperature (Atkinson et al., 1985) and average ambient ozone concentration
of lxlO~12 molecules/cm3 (U.S. EPA, 1987).
2.1.3. Reaction with Nitrate Radicals. The half-life for the nighttime
reaction of furan with nitrate radicals (nitrate radicals are unstable to
sunlight) In the atmosphere was calculated to be 34 minutes, using an
experimentally determined reaction rate constant of 1.4xlO~12 cmVmole-
cule-sec at room temperature and an average ambient nitrate radical concen-
tration of 2.4x10" molecules/cm3 during nighttime hours (Atkinson et
0067d -4- 09/25/87
-------
al., 1985). By analogy to alkenes and dlalkenes, nitrate radical reaction
with furan Is expected to proceed Initially by addition of the NO- radical
0
to the oleflnlc double bonds, followed by rapid addition of 0? to yield a
peroxy radical. Reaction of the peroxy radical with NO- can then yield
the thermally unstable peroxynltrates. Although the ultimate fate of the
peroxy radical 1s not known, H 1s likely that ring cleavage would
eventually occur, resulting In such species as CHOCH=CHOCHO (Atkinson et
al., 1985).
2.1.4. Physical Removal Processes. Reaction of furan with hydroxyl
radicals or nitrate radicals 1s expected to HmU the Importance of wet
deposition as an atmospheric removal process. Furthermore, most furan
removed by wet deposition Is likely to reenter the atmosphere by volatiliza-
tion (Section 2.2.4.).
2.2. WATER
2.2.1. Hydrolysis. Based on the molecular structure, furan 1s expected
to be resistant to chemical hydrolysis under environmental conditions (Lyman
et al., 1982).
2.2.2. Bloaccumulatlon. BCFs of 3.4-6.1 were estimated using a log K
of 1.34 (Hansch and Leo, 1985), a water solubllHy(S) of 1.01x10* mg/i
at 25°C (Valvanl et al., 1981) and the following linear regression equations
(Lyman et al., 1982):
log BCF = 0.76 log K - 0.23 (2-1)
log BCF = 2.791 - 0.564 log S (2-2)
These BCFs suggest that bloaccumulatlon In aquatic organisms 1s not a
significant environmental fate process for furan.
2.2.3. Adsorption. Estimated KQC values of 27-128 (Section 2.3.1.)
suggest that physical adsorption of furan to sediments and suspended sol Ids
In water would not be significant.
0067d -5- 10/02/87
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2.2.4. Volatilization. Henry's Law constant for furan was estimated to
be 5.3xlO~3 atm-mVmol at 25°C using a vapor pressure of 600 mm Hg at
25°C (Boubllk et al., 1984) and a water solubility of l.OlxlO4 mg/8, at
25°C (Valvanl et al., 1981). Based on this value of Henry's Law constant
the half-life for furan volatilizing from a typical river 1 m deep, flowing
1 m/sec, with a wind speed of 3 m/sec was estimated to be 2.5 hours, using
the method of Lyman et al. (1982). Therefore, volatilization Is expected to
be the primary transport process for furan In water.
2.2.5. Blodegradatlon. Pertinent data regarding the blodegradatlon of
furan 1n water could not be located 1n the available literature as dted In
Appendix A.
2.3. SOIL
2.3.1. Leaching. K values of 27-128 were estimated for furan, using
a log K value of 1.34 (Hansch and Leo, 1985), a water solubility of
1.01x10* mg/l at 25°C and the following linear regression equations
(Lyman et al., 1982):
log KQC = -0.55 log S + 3.64 (2-3)
log KQC = 0.544 log KQW + 1.377 (2-4)
These K values suggest that furan would be highly mobile In soil and
susceptible to significant leaching In the absence of significant blotlc or
abiotic degradation processes (Swann et al., 1983).
2.3.2. Volatilization. The relatively high vapor pressure of furan (600
mm Hg at 25°C) (Boubllk et al., 1984) suggests that this compound would
volatilize fairly rapidly from dry soil surfaces. It appears that volatili-
zation of furan from moist soil surfaces would also be rapid since the
compound does not have a tendency to adsorb to soil and It was predicted to
volatilize rapidly from water (see Sections 2.2.4. and 2.3.1.).
0067d -6- 09/25/87
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2.4. SUMMARY
If released to the atmosphere, furan 1s expected to exist almost
entirely 1n the vapor phase. Reaction with photochemlcally generated
hydroxyl radicals 1s predicted to be the primary removal mechanism during
daylight (half-life, 2-6 hours) and reaction with nitrate radicals Is
predicted to be the primary removal mechanism (half-life, -1/2 hour) during
nighttime. Removal from the atmosphere by reaction with ozone or physical
processes 1s expected to be relatively Insignificant. If furan 1s released
to water, volatilization 1s expected to be an Important, 1f not the
dominant, removal mechanism. The volatilization half-life of furan 1n a
typical river 1 m deep, flowing 1 m/sec, with a wind speed of 3 m/sec was
estimated to be 2.5 hours (see Section 2.2.4.). Chemical hydrolysis,
bloaccumulatlon 1n aquatic organisms and physical adsorption to suspended
solid or sediments are not expected to be Important fate processes. If
released to moist soil, furan may be susceptible to rapid volatilization.
In the absence of significant blotlc or abiotic processes, residual furan In
moist soils Is susceptible to significant leaching to groundwater. If
released to dry soil, furan may volatilize rapidly.
0067d -7- 09/25/87
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3. EXPOSURE
The National Occupational Hazard Survey (NOHS), prepared by NIOSH during
1972-1974, estimates that 6804 workers may be exposed to furan 1n
occupational settings, annually (NIOSH, 1984).
3.1. WATER
Limited data are available on the detection of furan 1n water samples.
This compound has been qualitatively Identified 1n Gill Creek and Bloody Run
Creek, part of the Niagara River watershed (Elder et al., 1981), and 1n the
Niagara River (Great Lakes Water Quality Board, 1983). This compound was
detected 1n aqueous condensate samples from low-Btu gasification of Rosebud
coal at a concentration of 7+4 ppb; however, It was not detected (detection
limit 0.1 ppb) 1n groundwater or coal steam water before in situ coal
gasification, product water samples obtained during jji situ coal gasifi-
cation, Omega 9 retort water from \n situ oil shale processing or boiler
blowdown water from In situ oil shale processing (PelUzzarl et al., 1979).
3.2. FOOD
Furan can be found 1n a great variety of food products and beverages,
especially 1n heated food products, contributing to the flavor of these
foods (Stlch et al., 1981). Furan has been qualitatively Identified In 1 of
12 samples of mothers' milk obtained from women from four different urban
areas (PelUzzarl et al., 1982). This compound was also Identified as a
volatile component of roasted filberts (K1nl1n et al., 1972).
3.3. INHALATION
Furan has been Identified as a gas-phase component of cigarette smoke
(Sakuma et al., 1975), wood smoke (Klelndlenst et al., 1986), exhaust gas
from dlesel and gasoline engines (Hampton et al., 1982) and volatile
emissions from sorb trees (Isldorov et al., 1985). Furan was detected 1n
0067d -8- 10/02/87
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the expired air of two out of three male smokers and four out of five male
nonsmokers from Brooks A1r Force Base, TX. The rate of expiration ranged
from 0.25-98 yg/hour for smokers and 0.33-28 yg/hour for nonsmokers
(Conkle et al., 1975). This compound, also Identified In the expired air of
male and female nonsmokers from Chicago, IL, was found 1n 15 of 387 expired
air samples (mean concentration 0.547 ng/i) taken from 54 subjects
(Krotoszynskl et al., 1979). Since furan Is a volatile compound, 1t Is
likely that workers Involved In the use or handling of this compound would
be exposed by Inhalation.
3.4. DERMAL
Pertinent data regarding exposure to furan by dermal contact could not
be located 1n the available literature as cited 1n Appendix A.
3.5. SUMMARY
The most probable route of human exposure to furan Is by Inhalation.
Infants may be exposed to this compound by Ingestlon of mother's milk, since
1t was detected 1n 1 of 12 samples of mother's milk (PelUzzarl et al.,
1982). Furan has been Identified as a volatile component of roasted
filberts (Klnlln et al., 1972), and as a gas-phase component of cigarette
smoke (Sakuma et al., 1975), wood smoke (Klelndlenst et al., 1986), exhaust
gas from delsel and gasoline engines (Hampton et al., 1982) and volatile
emissions from sorb trees (Isldorov et al., 1985). Furan was detected In
the expired air of two out of three male smokers and four out of five male
nonsmokers from Brooks Air Force Base, TX. The rate of furan expiration
ranged between 0.25-98 for smokers and 0.33-28 yg/hour for nonsmokers
(Conkle et al., 1975). This compound has also been detected 1n the expired
air from male and female nonsmokers from Chicago, IL (Krotoszynskl et al.,
1979). This compound has been qualitatively Identified In the Niagara River
0067d -9- 10/02/87
-------
and two creeks In the Niagara River watershed (Elder et al., 1981; Great
Lakes Water Quality Board, 1983).
0067d -10- 10/02/87
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4. AQUATIC TOXICITY
4.1. ACUTE TOXICITY
The aquatic toxldty data base for furan 1s limited. Velth et al.
(1983) reported a 96-hour LC5Q of 61 mg/9. for fathead minnows,
Plmephales promelas. 1n a continuous flow bloassay.
4.2. CHRONIC EFFECTS
The only Information concerning chronic toxldty of furan was provided
by Call et al. (1985) who conducted continuous flow bloassays with early
life stages of fathead minnows exposed to contaminants for 31-33 days. In
this study, the NOEC was 8.27 mg/l. The LOEC was 12.2 mg/l. which
resulted 1n significant reductions 1n growth 1n terms of length and weight.
Based on these results, the authors estimated an MATC, which was the
geometric mean of NOEC and LOEC, of 10.0 mg/9..
4.3. PLANT EFFECTS
Pertinent data regarding effects of furan on aquatic plants could not be
located 1n the available literature as cited 1n Appendix A.
4.4. SUMMARY
Little Information was available concerning toxldty of furan to aquatic
biota. Velth et al. (1983) reported a 96-hour LC5Q of 61 mg/l for
fathead minnows. Call et al. (1985) calculated an MATC of 10.0 mg/t based
on a NOEC of 8.27 mg/l and a LOEC of 12.2 mg/t from a 31-33 day fathead
minnow early life stage test.
0067d -11- 10/02/87
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5. PHARMACOKINETICS
Pertinent Information regarding the pharmacoklnetlcs of furan was
limited.
5.1. ABSORPTION
Egle and Gochberg (1979) Investigated absorption of furan vapor by the
respiratory tracts of mongrel dogs weighing 9-23 kg. Total respiratory
tract, lower tract and upper tract (proximal to the tracheal bifurcation)
retention was measured 1n dogs anesthetized with pentobarbltal and allowed
to breath spontaneously from a resplrometer, or artificially ventilated 1n
the case of upper tract determinations. Percent retention was estimated as
the difference between the amount of material Inspired and expired or
recovered at the end of the trachea. Total tract retention was estimated at
90.8-95.3X for Inspired concentrations of 0.4-0.6 jig/ma (400-600
mg/m3). Lower tract retention ranged from 87.3-93.2X, which 1s Inversely
related to ventilation rate. Upper tract retention ranged from 85.4-89.9%,
and apparently Identical values were obtained from one-way (furan-contalnlng
air moving 1n one direction) and two-way (air movement 1n both directions)
experiments. Retention varied Inversely with ventilation rate, which ranged
from 6-18 cycles/minute.
5.2. DISTRIBUTION
Furan was distributed to the lungs, kidney and liver of mice following
1ntraper1toneal Injection. Gamma! et al. (1984) and Wiley et al. (1984)
administered a 4.1 mmol/kg (-279 mg/kg) dose of furan In sesame oil by
Intraperltoneal Injection to young adult male ICR mice, and measured the
concentration of furan In the lung, Hver and kidney at 1, 2 and 5 hours
after treatment. Peak levels 1n the lung and liver of -200 nmols/g of
0067d -12- 10/02/87
-------
tissue (-14 yg/g tissue) were observed at the 1-hour sampling. In the
kidney, a concentration of -110 nmol/g (-7.5 v9/g) at 1 hour Increased to
-500 nmol/g (-34 jig/g) by 2 hours after treatment. Terminal concentra-
tions (5 hours) 1n liver and kidney had declined to -50 nmol/g (-3.4 jig/g)
and In lung, to -100 nmol/g (~7 pg/g).
5.3. METABOLISM
Studies specifically designed to Identify metabolites of furan could not
be located 1n the available literature as cited 1n Appendix A. Masuda et
al. (1984), however, reported that furan-1nduced nephrotoxlclty 1n mice was
Increased when mice were pretreated with carbon tetrachloHde, a toxicant
that selectively destroys the metabolic function of the liver. The Investi-
gators concluded that more unmetabollzed furan was available for transforma-
tion to nephrotoxlc compound(s) by the kidney. Administration of dlethyl-
dlthlocarbamate or carbon dlsulflde, known Inhibitors of the mlcrosomal
enzyme system of the liver and kidney, reduced the nephrotoxlclty of furan
1n untreated or carbon tetrachloMde treated mice. The Investigators
hypothesized that dlethyldlthlocarbamate and carbon dlsulflde acted directly
on the kidney to suppress the metabolic activation of furan to nephrotoxlc
compound(s).
5.4. EXCRETION
Pertinent data regarding the excretion of furan could not be located In
the available literature as dted 1n Appendix A.
5.5. SUMMARY
Information regarding the pharmacoklnetlcs of furan was limited. The
available data Indicate that furan 1s absorbed extensively by the Inhala-
tion route (Egle and Gochberg, 1979) and was distributed to the lungs,
0067d -13- 10/02/87
-------
kidney and liver following 1ntraper1toneal Injection (Gamma! et al., 1984;
Wiley et al., 1984). Metabolic activation may be required for furan Induced
toxlclty (Masuda et al., 1984).
0067d -14- 10/02/87
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposures. Pertinent data regarding the subchronlc and
chronic toxlclty of furan as a result of Inhalation exposure could not be
located In the available literature as dted 1n Appendix A.
« .
6.1.2. Oral Exposures.
6.1.2.1. SUBCHRONIC — SRI (1982a,b) conducted subchronlc gavage
studies on furan and used F-344 rats and B6C3F1 mice for 13 weeks at doses
ranging from 0-60 mg/kg furan In corn oil, 5 days/week. Groups of 10 male
and 10 female rats and 10 female mice received doses of 60, 30, 15, 8, 4 and
0 mg/kg. Groups of 10 male mice received doses of 30, 15, 8, 4, 2 and 0
mg/kg. Gross necropsy was performed on all animals and data regarding
mortality, body weight, organ weights, and clinical and hlstopathologlcal
signs of toxldty were evaluated. Complete hlstopathology was performed on
all rats at the 60 and 30 mg/kg levels, all control rats and mice, female
mice at the 60 mg/kg level and male mice at the 30 mg/kg level. Clinical
signs of toxldty were mostly confined to male and female rats and female
mice 1n the high-dose (60 mg/kg) group. Mortality occurred 1n 9/10 male and
4/10 female rats at the high-dose level. High-dose male and female rats and
high-dose (30 mg/kg) male mice had treatment-related reduced rates of body
weight gain. In rats, a dose-related Increase In liver size was reported In
all treated groups of males and 1n all but the low-dose group of females.
Hlstopathologlcal examination revealed a dose-related Increased severity In
liver lesions In the rats, with mild to minimal lesions observed at 4 mg/kg,
the lowest level tested. Liver alterations associated with administration
of furan Included cytomegaly, degeneration, necrosis and nodular hyperplasla
of the hepatocytes, liholanglofIbrosls, hyperplasla of the bile duct
epithelium and a pigment deposition In Kupffer cells. Additional lesions
0067d -15- 10/02/87
-------
found only In high-dose animals that were considered treatment related were
atrophy of the thymus and gonads, renal tubular dilatation and degeneration
and necrosis of the renal tubular epithelium.
In mice, treatment-related Increases 1n IWer weight were reported In
males at a dose of ^>15 mg/kg and In females at doses of >30 mg/kg. The
hlstopathologlcal examination revealed a dose-related toxic hepatitis at >15
mg/kg 1n females and at >8 mg/kg In males. Liver lesions were not found In
male mice receiving doses of <4 mg/kg and 1n female mice receiving doses of
<8 mg/kg. In addition to the hepatic alterations reported above In rats,
other liver changes reported In mice were focal flbrosls, focal cytologlcal
alteration, focal necrosis and focal supportive Inflammation.
6.1.2.1. CHRONIC -- Results of an ongoing 2-year NTP-sponsored
carcinogenic gavage bloassay In rats and mice are currently not available
(NTP, 1987). This study may provide Information concerning the chronic
toxldty of furan.
6.1.3. Other Relevant Information. In an abstract from a Russian Study,
values of 4.2, 2.8 and 1.8 mg/l were reported for LC,., LC and
LC1&, respectively, In albino rats (Stasenkova and Kochetkova, 1968). The
length of exposure was not reported. Sax (1984) reported an Inhalation
LC5Q of 120 mg/m3 In mice for a 1-hour exposure and an 1ntraper1toneal
LOcQ of 5200 tig/kg for rats. Egle and Gochberg (1979) reported
Intraperltoneal L05Q values of 5.2 mg/kg for rats and 7.0 mg/kg for mice.
6.2. CARCINOGENICITY
6.2.1. Inhalation and Oral. Pertinent data regarding the carclnogenlclty
of furan by oral or Inhalation exposure routes could not be located 1n the
available literature as dted 1n Appendix A. According to a recent Manage-
ment Status Report (NTP, 1987), NTP Is currently evaluating hlstopathologl-
cal data from a chronic gavage study with rats and mice.
0067d -16- 10/02/87
-------
6.2.2. Other Relevant Information. Other relevant Information regarding
the cardnogenlclty of furan could not be located In the available litera-
ture as cited In Appendix A.
6.3. MUTAGENICITY
Mortelmans et al. (1986) reported negative results 1n strains TA100,
1535, 1537 and 98 of Salmonella typhlmurlum when tested by plate Incorpora-
tion at doses of furan ranging from 33.3-3333.3 yg/plate, both 1n the
presence and absence of S-9, which was purified from livers of rats and
hamsters following Aroclor 1254 pretreatment and contained metabolic
activation system. Ebrlnge et al. (1979) also reported that furan was not
rnutagenlc when tested 1n assays with Salmonella typhlmurlum and Euqlena
gradHs. When furan was added to Chinese hamster ovary cell cultures,
Stlch et al. (1981) reported a concentration-related Increase 1n the
Incidence of chromatld breaks and exchanges 1n dlplold metaphase cell only
In the presence of metabolic activation. Concentrations tested ranged from
-25-225 mM.
6.4. IERATOGENICITY
Pertinent data regarding the teratogenlclty of furan could not be
located 1n the available literature as dted 1n Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding other reproductive effects of furan could not
be located In the available literature as cited 1n Appendix A.
6.6. SUMHARY
Dose-related toxic hepatitis was reported 1n both sexes of F-344 rats
and B6C3F1 mice when furan was administered by gavage for 13 weeks (SRI,
1982a,b). The liver lesions were considered minimal In low-dose rats and
did not occur In the two lowest dose groups of male and female mice.
0067d -17- 09/25/87
-------
High-dose male and female rats and high-dose male mice had reduced body
weight gains. Dose-related Increase 1n liver weight was reported In all
treated rats except low-dose females and In male and female mice at the two
highest dose levels.
Pertinent data regarding the cardnogenlclty, teratogenlclty or other
reproductive effects of furan could not be located 1n the available litera-
ture as cited 1n Appendix A. Furan was reported to be nonmutagenlc when
tested In the presence and absence of S-9 1n assays with Salmonella typhl-
murlum and Euglena qraclHs (Mortelmans et a!., 1986; EbMnge et al., 1979).
Furan was clastogenlc to Chinese hamster ovary cells when cultured 1n the
presence of S-9 (Stlch et al., 1981).
0067d -18- 10/02/87
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
Pertinent guidelines and standards, Including EPA ambient water and air
quality criteria, drinking water standards, FAO/WHO ADIs, EPA or FDA toler-
ances for raw agricultural commodities or foods, and ACGIH, NIOSH or OSHA
»
occupational exposure limits could not be located In the available litera-
ture as cited In Appendix A. U.S. EPA (1986c) has verified a chronic oral
RfD of 0.1 mg/day for furan, based on a NOAEL of 2 mg/kg from a mouse
subchronlc oral gavage study (SRI, 1982b).
7.2. AQUATIC
Guidelines and standards for the protection of aquatic organisms from
the effects of furan could not be located In the available literature as
cited 1n Appendix A.
0067d -19- 10/02/87
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
Hlstopathologlcal examination regarding the carclnogenldty of furan Is
currently In progress for the 2-year NTP gavage study using rats and mice
(NTP, 1987); therefore, lack of data precludes quantitative assessment.
» »
However, sufficient data are available for derivation of an RfD for oral
exposure.
8.1.1. Weight of Evidence. Since no data are currently available regard-
ing the cardnogenlclty of furan to humans or animals, H Is classified as
an EPA Group D compound (U.S. EPA, 1986d).
8.1.2. Quantitative Risk Estimates. Insufficient Information precludes
the derivation of quantitative risk estimates for the cardnogenlclty of
furan by either oral or Inhalation exposure.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure. Pertinent data regarding the toxlclty of
furan by the Inhalation route could not be located In the available litera-
ture as cited In Appendix A. RfDs for Inhalation exposure cannot be derived.
8.2.2. Oral Exposures.
8.2.2.1. LESS THAN LIFETIME (SUBCHRONIC) — An RfD for furan was
previously derived and verified by U.S. EPA (1986c) from oral exposure data
reported by SRI (1982a,b). The study was discussed 1n Section 6.1.2.1. and
the following risk assessment was presented by U.S. EPA (1986c).
SRI (1982a,b) conducted a 13-week gavage study using groups of 10 male
and female F-344 rats and 10 female B6C3F1 mice treated 5 days/week with
doses of 0, 4, 8, 15, 30, and 60 mg/kg furan In corn oil. Male mice,
however, were administered with doses of 0, 2, 4, 8, 15 and 30 mg/kg. Data
regarding mortality, body weight, organ weights, and clinical and
h1stopatholog1cal signs of toxlclty were evaluated. High-dose male and
0067d -20- 10/02/87
-------
female rats and high-dose male mice had treatment-related reduced rates of
body weight gain. H1stopatholog1cal examination In rats revealed a
dose-related Increased severity In liver lesions, with lesions observed at
the low-dose level considered minimal to mild. A dose-related Increase 1n
liver weight was also reported In all treated groups of males and all but
the low-dose group of female rats. In mice, treatment-related Increases 1n
liver weight occurred 1n males at >15 mg/kg and 1n females at >30 mg/kg.
H1stopatholog1cal evaluation revealed dose-related toxic hepatitis In male
mice at doses of >8 mg/kg and 1n female mice at doses of >15 mg/kg.
The SRI (1982a) data Indicate that the rat study failed to define a
threshold for toxic hepatitis, which was the critical effect 1n the target
organ for the toxlclty of furan. The mouse study (SRI, 1982b) Identified a
threshold for toxic hepatitis of 4 mg/kg, the highest dose 1n males at which
lesions did not occur; mild lesions of toxic hepatitis occurred at 8 mg/kg
\n males. In females, lesions of toxic hepatitis were reported at 15 mg/kg
but not 8 mg/kg. Since lesions of toxic hepatitis were present 1n rats at 4
mg/kg, the highest NOAEL Identified for both species was 2 mg/kg In the male
mice. Since the treatment was performed 5 days/week, the 2 mg/kg dose 1s
transformed to an equivalent dose of 1.4 mg/kg/day. Applying an uncertainty
factor of 100 to the mouse NOAEL of 1.4 mg/kg/day results In a subchronlc
oral RfD of 0.01 mg/kg/day, or 1 mg/day for a 70 kg human. The uncertainty
factor of 100 was selected based on a factor of 10 to account for
Interspedes extrapolation and another factor of 10 to protect the unusually
sensitive Individuals of the population. The confidence In the RfD 1s
considered medium since the critical study provided adequate toxlclty
endpolnts 1n a well-designed multlspecles oral study, but data were not
0067d -21- 10/02/87
-------
available regarding the cardnogenldty, developmental or reproductive
toxIcHy of furan. Availability of the data from the NTP chronic gavage
bloassay may change the RfD and the level of confidence (NTP, 1987).
8.2.2.2. CHRONIC EXPOSURES -- No pertinent data are available regard-
ing the chronic oral exposure of furan to animals or humans; however, a
chronic oral RfD can be derived from the subchronlc RfD by applying an
additional uncertainty factor of 10 for extrapolation from subchronlc to
chronic exposure. Applying an uncertainty factor of 1000 to the mouse NOAEL
of 1.4 mg/kg/day results In a chronic oral RfD of 1 yg/kg/day, or 0.1
mg/day for a 70 kg man. A medium level of confidence 1n the RfD reflects
the confidence In the key study and the total data base for furan.
0067d -22- 10/02/87
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The effects of subchronlc oral exposure to furan were discussed In
Section 6.1.2.1. and data for derivation of CSs are summarized 1n Table 9-1.
These data Indicate three types of toxic effects associated with exposure to
furan. Mortality occurred In rats of both sexes In the 60 mg/kg group.
Degenerative, necrotlc and hyperplastlc liver lesions, assigned an RV of
8, occurred In male and female rats at 8 mg/kg, In male mice at 8 mg/kg and
In female mice at 15 mg/kg. Minimal or mild liver lesions, assigned an
RV of 6, occurred In male and female rats at 4 mg/kg. CSs are calculated
for each of these effects In Table 9-2 using the data that generate the
lowest equivalent human dose. The largest CS, 37.6, which corresponds to an
RQ of 100 pounds and 1s associated with degenerative, necrotlc and
hyperplastlc liver lesions In male mice, Is chosen to represent the chronic
toxldty of furan (Table 9-3).
9.2. BASED ON CARCINOGENICITY
Pertinent data regarding the carclnogenlcHy of furan could not be
located 1n the available literature as cited In Appendix A. Because hlsto-
pathology from a 2-year oral gavage study using rats and mice Is currently
In progress, the data are unavailable (NTP, 1987). Therefore, Insufficient
.data preclude the derivation of carcinogenic potency factors. Furan Is
assigned to EPA Group D, not classifiable as to carclnogenldty. Hazard
ranking based on carclnogenldty 1s not possible.
0067d -23- 10/02/87
-------
TABLE 9-1
Oral Toxlclty Summary for Furan
Q.
1
*•
1
O
O
ro
Species/
Strain
Rat/Fischer
344
Rat/Fischer
344
Rat/Fischer
344
Rat/Fischer
344
Rat/Fischer
344
Rat/Fischer
344
Nouse/B6C3Fl
Nouse/B6C3Fl
'Calculated
bTrans formed
Calculated
Sex/
Number
N/10
N/10
N/10
F/10
F/10
F/10
N/10
F/10
Average Body
Weight'
(kg)
0.165
0.296
0.298
0.151
0.183
0.179
0.034
0.025
from weekly group average body
Purity/
Vehicle
>98X/
corn oil .
>98X/
corn oil
>98X/
corn oil
>98X/
corn oil
>98X/
corn oil
>98X/
corn oil
>98X/
corn oil
>98X/
corn oil
weight data
dosage calculated by expanding treatment
by multiplying
Exposure
60 mg/kg.
5 days/week,
13 weeks
8 mg/kg.
5 days/week,
13 weeks
4 mg/kg.
5 days/week,
13 weeks
60 mg/kg.
5 days/week,
13 weeks
8 mg/kg.
5 days/week,
13 weeks
4 mg/kg.
5 days/week.
13 weeks
8 mg/kg.
5 days/week.
13 weeks
15 mg/kg.
5 days/week.
13 weeks
Transformed
Animal Dose0
(mg/kg/day)
42.9
5.7
2.9
42.9
5.7
2.9
5.7
10.7
Equivalent
Human Dosec Response
(mg/kg/day)
5.71 Mortality
0.92 Degenerative, necrotlc.
hyperplastlc lesions In
liver
0.47 Nlld liver lesions
5.54 Mortality
0.79 Degenerative, necrotlc.
hyperplastlc lesions In
liver
0.40 Nlld liver lesions
0.45 Degenerative, necrotlc.
hyperplastlc lesions In
liver
0.76 Degenerative, necrotlc,
hyperplastlc lesions In
liver
Reference
SRI. 19823
SRI, 19823
SRI. 19823
SRI. 19823
SRI. 19823
SRI. 19823
SRI, 1982b
SRI. 1982b
provided by Investigators.
over a 7 -day week.
the animal dosage by the cube root of the ratio of the animal
to human reference body weight (70 kg).
00
-------
o
—J
Q.
TABLE 9-2
Oral Composite Scores for Furan
Species Animal Dose
(mg/kg/day)
t Rat 42.9
^Mouse 5.7
Rat 2.9
Human MED*
(rag/day)
38.8
3.2
2.8
RVd
3.1
4.7
4.8
Effect RVe CS
Mortality 10 31
Degenerative. 8 37.6
necrotlc,
hyperplastlc
liver lesions
Mild liver 6 28.8
lesions
RQ Reference
100 SRI. 1982a
100 SRI. 1982b
100 SRI. 1982a
'Calculated by multiplying the equivalent human dose expressed In mg/kg/day by 70 kg and applying a factor
of 10 to expand from subchronlc to chronic exposure.
o
\
CO
-------
TABLE 9-3
Furan
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: oral/gavage
Dose*: 3.2 mg/day
Effect: degenerative, necrotlc, hyperplastlc liver lesions
Reference: SRI, 1982b
RVd: 4.7
RVe: 8
Composite Score: 37.6
RQ: 100
'Equivalent human dose
0067d -26- 10/02/87
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SRI (Stanford Research Institute). 1986. 1986 Directory of Chemical
Producers: United States of America SRI International, Menlo Park, CA.
0067d -31- 10/02/87
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Stasenkova, K.P. and T.A. Kochetkova. 1968. Comparative evaluation of
toxlclty In a series of furan compounds. Tokslkol. Nov. Prom. Khlm.
Veshchestv, No. 10, 35-44.
Stlch, H.F., M.P. Rosin, C.H. Wu and W.D. Powrle. 1981. ClastogenlcHy of
furans found In food. Cancer Lett. 13(2): 89-95.
Swann, R.L., D.A. Laskowskl, P.J. McCall, K. Vander Kuy and H.J. Dlshburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
U.S. EPA. 1980. Guidelines and Methodology Used In the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 79347-79357.
U.S. EPA. 1984. Methodology and Guidelines for Reportable Quantity
Determinations Based on Chronic Toxlclty Data. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1986a. Methodology for Evaluating Potential Carclnogenlclty 1n
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
Prepared by the Office of Health and Environmental Assessment, Carcinogen
Assessment Group, for the Office of Solid Waste and Emergency Response,
Washington, DC.
0067d -32- 10/02/87
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U.S. EPA. 1986b. OHMTAOS (011 and Hazardous Material Technical Assistance
Data Systems). Data base. On-Hne.
U.S. EPA. 1986c. Integrated Risk Information System (IRIS). Reference
dose (RfD) for oral exposure for furan. Online (Revised; verification date
11/16/86). Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1986d. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1987. Graphical Exposure Modeling System (GEMS). Fate of
atmospheric pollutants (FAP). Office of Toxic Substances, U.S. EPA,
Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic Organic
Chemicals, United States Production and Sales, 1985. USITC Publ. 1745,
Washington, DC.
Valvanl, S.C., S.H. Yalkowsky and T.J. Roseman. 1981. Solubility and
partitioning. IV. Aqueous solubility and octanol-water partition coeffi-
cients of liquid nonelectrolytes. J. Pharm. Scl. 70: 502-507.
_Ve1th, G.D., D.J. Call and L.T. Brooke. 1983. Structure-toxlclty relation-
ships for the fathead minnow, Plmephales promelas: Narcotic Industrial
chemicals. Can. J. F1sh. Aquat. Sc1. 40(6): 743-748.
0067d -33- 10/02/87
-------
Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemicals,
2nd ed. Van Nostrand Relnhold Co., New York, NY.
Wiley, R.A., G.J. Tralger, S. Baraban and L.M. Gammal. 1984. Toxldty-
d1str1but1on relationships among 3-alkylfurans In mouse liver and kidney.
Toxlcol. Appl. Pharmacol. 74(1): 1-9.
Wlndholz, M., Ed. 1983. The Herck Index. An Encyclopedia of Chemicals,
Drugs and Blologlcals, 10th ed. Merck and Co., Inc., Rahway, NJ. p. 613.
0067d -34- 10/02/87
-------
Stasenkova, K.P. and T.A. Kochetkova. 1968. Comparative evaluation of
toxlclty In a series of furan compounds. Tokslkol. Nov. Prom. Kh1m.
Veshchestv, No. 10, 35-44.
Stlch, H.F., M.P. Rosin, C.H. Wu and W.D. Powrle. 1981. Clastogenldty of
furans found 1n food. Cancer Lett. 13(2): 89-95.
Swann, R.L., D.A. Laskowskl, P.J. McCall, K. Vander Kuy and H.J. Dlshburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 49347-49357.
U.S. EPA. 1984. Methodology and Guidelines for Reportable Quantity
Determinations Based on Chronic Toxlclty Data. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Haste and Emergency Response,
Washington, DC.
U.S. EPA. 1986a. Methodology for Evaluating Potential Carc1nogen1c1ty In
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
Prepared by the Office of Health and Environmental Assessment, Carcinogen
Assessment Group, for the Office of Solid Waste and Emergency Response,
Washington, DC.
0067d -32- 10/02/87
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APPENDIX A
LITERATURE SEARCHED
This HEED Is based on data Identified by computerized literature
searches of the following:
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXBACK 76
TOXBACK 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
These searches were conducted In February, 1987. In addition, hand searches
were made of Chemical Abstracts (Collective Indices 5-9), and the following
secondary sources should be reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986-1987. TLVs: Threshold Limit Values for Chemical Substances 1n
the Work Environment adopted by ACGIH with Intended Changes for
1986-1987. Cincinnati, OH. Ill p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 28. John Wiley and
Sons, NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
0067d -35- 10/02/87
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Grayson, M. and 0. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. MHO, IARC, Lyons, France.
Jaber, H.M., W.R. Mabey, A.T. Lieu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
SRI International, Menlo Park, CA. EPA 600/6-84-010. NTIS
PB84-243906.
NTP (National Toxicology Program). 1986. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1986. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report 1n the Special Review
Program, Registration Standards Program and the Data Call In
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1985. CSB Existing Chemical Assessment Tracking System.
Name and CAS Number Ordered Indexes. Office of Toxic Substances,
Washington, DC.
USITC (U.S. International Trade Commission). 1985. Synthetic
Organic Chemicals. U.S. Production and Sales, 1984, USITC Publ.
1422, Washington. DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc.. Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0067d -36- 10/02/87
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_ In addition, approximately 30 compendia of aquatic toxldty data were
reviewed, Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and H.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxldty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, F1sh and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
0067d -37- 10/02/87
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APPENDIX B
Summary Table for Furan
Species
Inhalation Exposure
Subchronlc ID
Chronic ID
Carclnogenlclty ID
l^ Oral Exposure
CO
Subchronlc mice
Chronic mice
Carclnogenlclty ID
REPORTABLE QUANTITIES
_, Based on Chronic Toxldty:
o
\
S Based on Carclnogenlclty:
on
Exposure
ID
ID
ID
2 mg/kg.
5 days/week,
13 weeks
2 mg/kg,
5 days /week,
13 weeks
ID
too
ID
Effect
ID
ID
ID
toxic
hepatitis
toxic
hepatitis
ID
RfD or q-j* Reference
ID ID
ID ID
ID ID
1 mg/day SRI, 1982b
0.1 mg/day SRI. 1982b
ID ID
SRI. 1982b
ID = Insufficient data
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