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U.S. Environmental Protection Agency
Chemical Assessment Summary
National Center for Environmental Assessment
1
Furan; CASRN 110-00-9
Human health assessment information on a chemical substance is included in the IRIS database
only after a comprehensive review of toxicity data, as outlined in the
IRIS assessment
development process
. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and
II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached
during the assessment development process. Supporting information and explanations of the
methods used to derive the values given in IRIS are provided in the
guidance documents located
on the IRIS website
.
STATUS OF DATA FOR Furan
File First On-Line 01/31/1987
Category (section)
Assessment Available?
Last Revised
Oral RfD (I.A.)
yes
01/31/1987
Inhalation RfC (I.B.)
not evaluated
Carcinogenicity Assessment (II.)
not evaluated
I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Furan
CASRN — 110-00-9
Last Revised — 01/31/1987
The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic
effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an
estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the
human population (including sensitive subgroups) that is likely to be without an appreciable risk
of deleterious effects during a lifetime. Please refer to the Background Document for an
elaboration of these concepts. RfDs can also be derived for the noncarcinogenic health effects of
substances that are also carcinogens. Therefore, it is essential to refer to other sources of
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2
information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation will be contained in
Section II of this file.
I.A.1. Oral RfD Summary
Critical Effect
Experimental Doses*
UF
MF
RfD
Hepatic lesions
Mouse Subchronic
Oral Study
NTP, 1982
NOAEL: 2 mg/kg converted
to 1.4 mg/kg/day on
5 days/7 days basis
LOAEL: 4 mg/kg/day (rat)
1000
1
1E-3
mg/kg/day
*Conversion Factors -- 5 days/week feeding schedule
I.A.2. Principal and Supporting Studies (Oral RfD)
NTP (National Toxicology Program). 1982. Subchronic toxicity report on furan in B6C3F1
mice. Prepared by Southern Research Institute under Contract No. 1- CP-95641-01 for NTP,
Bethesda, MD.
NTP (1982) performed a 13-week gavage study using mice and rats (10 animals/sex/group)
treated 5 days/week with furan in corn oil at 0-60 mg/kg. In this study, data on mortality, body
weight, organ weight, and clinical and histopathologic signs of toxicity were evaluated.
Clinical signs of toxicity were, for the most part, confined to male and female rats and female
mice in the high-dose (60 mg/kg) group. 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,
histopathologic examination revealed a dose-related increased severity in liver lesions; lesions
observed at the 4 mg/kg dose level were considered "minimal to mild." Measurement of relative
organ weights revealed a dose-related increase in liver size in all treated groups of males and in
all but the lowest dose (4 mg/kg) groups of female rats. In mice, relative organ weight
measurements suggest that treatment-related increases in liver weight occurred in male mice at
doses greater than or equal to 15 mg/kg and in females at doses greater than or equal to 30
mg/kg. Upon histopathologic examination, toxic hepatitis of dose- related severity was noted in
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male mice at doses greater than or equal to 8 mg/kg and in female mice at doses greater than or
equal to 15 mg/kg. Doses of 2 and 4 mg/kg/day were without toxic effect.
Examination of the NTP (1982) data indicated that the rat study failed to define a threshold for
toxic hepatitis, the major lesion in the target organ for the toxicity of furan. The mouse study
(NTP, 1982) indicated a threshold for toxic hepatitis, in that 2 and 4 mg/kg were doses in males
at which lesions did not occur; mild lesions of toxic hepatitis occurred at 8 mg/kg. In females,
lesions of toxic hepatitis were absent at 8 mg/kg and present at 15 mg/kg. Considering these data
together, a dose of 2 mg/kg/day is a reasonable choice for the NOAEL. Since treatment was
performed 5 days/week, the 2 mg/kg dose can be transformed to an equivalent dose of 1.4
mg/kg/day. By applying an uncertainty factor of 1000 to the mouse NOAEL of 1.4 mg/kg/day,
an oral RfD (ADI) of 1 ug/kg/day or 0.1 mg/day for a 70-kg human can be recommended.
I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 1000 was applied: 10 for extrapolation from subchronic to
chronic studies, 10 for interspecies extrapolation and another factor of 10 to provide added
protection for sensitive individuals.
MF — None
Availability of rat and mouse subchronic oral toxicity data provided a medium level of
confidence for the RfD. The National Toxicology Program (NTP, 1985) is currently evaluating
histopathologic data of a chronic gavage bioassay of furan in rats and mice. The data from this
study may change the RfD and the level of confidence.
I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
The principal study provided toxicologic parameters in well-designed subchronic studies in both
rats and mice and, thus, rated medium. The data base lacks supporting studies and is rated low.
Low confidence in the RfD follows.
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I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — None
Agency Work Group Review — 02/26/1986
Verification Date — 02/26/1986
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA
contractor of the more recent toxicology literature pertinent to the RfD for Furan conducted in
August 2003 did not identify any critical new studies. IRIS users who know of important new
studies may provide that information to the IRIS Hotline at
hotline.iris@epa.gov
or 202-566-
1676.
I.A.7. EPA Contacts (Oral RfD)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general,
at (202)566-1676 (phone), (202)566-1749 (FAX) or
hotline.iris@epa.gov
(internet address).
I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Furan
CASRN — 110-00-9
Not available at this time.
II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Furan
CASRN — 110-00-9
This substance/agent has not undergone a complete evaluation and determination under US
EPA's IRIS program for evidence of human carcinogenic potential.
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III. [reserved]
IV. [reserved]
V. [reserved]
VI. Bibliography
Substance Name — Furan
CASRN — 110-00-9
VI.A. Oral RfD References
NTP (National Toxicology Program). 1982. Subchronic toxicity report on furan in B6C3F1
mice. Prepared by Southern Research Institute under Contract No. 1- ES-95651-01 for NTP,
Bethesda, MD.
NTP (National Toxicology Program). 1985. Management Status Report dated 08/07/1985.
Bethesda, MD.
VI.B. Inhalation RfC References
None
VI.C. Carcinogenicity Assessment References
None
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VII. Revision History
Substance Name — Furan
CASRN — 110-00-9
Date
Section
Description
10/28/2003 I.A.6.
Screening-Level Literature Review Findings message has been added.
VIII. Synonyms
Substance Name — Furan
CASRN — 110-00-9
Last Revised — 01/31/1987
•
110-00-9
•
Divinylene oxide
•
Furan
•
Furfuran
•
Oxacyclopentadiene
•
Oxole
•
Tetrole
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