Phthalic anhydride (CASRN 85-44-9 )
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0308
Phthalic anhydride; CASRN 85-44-9
Health assessment information on a chemical substance is included in IRIS only after a comprehensive review of chronic toxicity data by U.S. EPA health scientists from several Program Offices and the Office of Research and Development. The summaries presented in Sections I and II represent a consensus reached in the review process. Background information and explanations of the methods used to derive the values given in IRIS are provided in the Background Documents.
STATUS OF DATA FOR Phthalic anhydride
File First On-Line 09/07/1988
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 09/07/1988 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data | 05/01/1992 |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Phthalic anhydride
CASRN — 85-44-9
Last Revised — 09/07/1988
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 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 |
---|---|---|---|---|
Lung and kidney Chronic Mouse NCI, 1979 |
NOAEL: None LOAEL: 12,019 ppm of |
1000
|
1
|
2E+0
mg/kg/day |
*Conversion Factors: mouse food consumption = 13% bw/day
__I.A.2. Principal and Supporting Studies (Oral RfD)
NCI (National Cancer Institute). 1979. Bioassay of phthalic anhydride for possible carcinogenicity. NCI Carcinogenesis Tech. Rep. Ser. No. 159. NTIS PB293594.
B6C3F1 mice, 50/sex/group, were fed diets containing phthalic anhydride for 104 weeks; initial concentrations were 25,000 and 50,000 ppm, but the levels were lowered to 12,500 and 25,000 for males and 6250 and 12,500 ppm for females after 32 weeks because of severe weight loss. The TWA concentrations were 16,346 and 32,692 ppm for the male mice and 12,019 and 24,038 ppm for the female mice. Groups of 20 mice of each sex served as untreated controls. Body weights were measured monthly and comprehensive gross and microscopic examinations were conducted on all animals up to death or sacrifice at termination of experiment. Treatment did not affect survival in either sex of mice, but there was a dose-related inhibition of weight gain; decreases at the end of the study were 12% and 25% in the males and 12% and 27% in the females. Although NCI (1979) concluded that there were no treatment-related nonneoplastic pathological effects in the mice, examination of the incidence data shows significantly increased incidences of lung and kidney lymphocytosis in the low-\and high-dose males and females, chronic bile duct inflammation in the high-dose males and females and dose-related adrenal atrophy and mineralization of the thalamus in the low-\and high-dose males. Thus, the 12,019 ppm level in female mice is the LOAEL, which when multiplied by a food factor of 0.13 kg food/kg bw yields a dose of 1562 mg/kg/day. Dividing the LOAEL by an uncertainty factor of 1000 yields a rounded RfD of 2 mg/kg/day, or 109 mg/day for a 70 kg human.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — 10 for interspecies extrapolation, 10 to protect sensitive subgroups of the human population, and 10 to extrapolate from a LOAEL.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
In the same NCI (1979) study F344 rats (50/sex/group) were fed diets containting 7500 or 15,000 ppm phthalic anhydride for 105 weeks. The mean body weights of the high-dose males were lower than the controls from week 13 to the end of the study, but the decrease was never more than 10%. There were no treatment-related effects on survival or pathology. Phthalic anhydride was reported to be teratogenic in mice following intraperitoneal injection, but teratogenicity or reproductive toxicity has not been studied using the oral route of exposure (Fabro et al., 1982).
__I.A.5. Confidence in the Oral RfD
Study — High
Database — Medium
RfD — Medium
Because the NCI (1979) bioassay is a well-designed feeding study in two species that defines a NOAEL and LOAEL, the confidence level is high. Confidence in the database is medium because teratogenicity has not been tested adequately. Confidence in the RfD is rated medium because of the lack of reproductive toxicity data.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — U.S. EPA, 1986
Other EPA Documentation — None
Limited Peer Review and Extensive Agency-wide Review, 1986
Agency Work Group Review — 02/24/1988
Verification Date — 02/24/1988
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 Phthalic anhydride conducted in September 2002 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 — Phthalic anhydride
CASRN — 85-44-9
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Phthalic anhydride
CASRN — 85-44-9
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Phthalic anhydride
CASRN — 85-44-9
Last Revised — 01/01/1990
_VI.A. Oral RfD References
Fabro, S., G. Shull and N.A. Brown. 1982. The relative teratogenic index and teratogenic potency: Proposed components of developmental toxicity risk assessment. Teratogen. Carcinogen. Mutagen. 2(1): 61-76.
NCI (National Cancer Institute). 1979. Bioassay of phthalic anhydride for possible carcinogenicity. NCI Carcinogenesis Tech. Rep. Ser. No. 159. NTIS PB293594.
U.S. EPA. 1986. Health and Environmental Effects Profile on Phthalic Anhydride. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Phthalic anhydride
CASRN — 85-44-9
Date |
Section |
Description |
---|---|---|
09/07/1988 | I.A. | Oral RfD summary on-line |
01/01/1990 | VI. | Bibliography on-line |
01/01/1992 | I.A.7. | Secondary contact changed |
01/01/1992 | IV. | Regulatory Action section on-line |
05/01/1992 | II. | Carcinogenicity assessment now under review |
08/01/1995 | II. | EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Phthalic anhydride
CASRN — 85-44-9
Last Revised — 09/07/1988
- 85-44-9
- 1,2-benzenedicarboxylic acid anhydride
- 1,3-dihydro-1,3-dioxoisobenzofurandione
- 1,3-phthalandion
- phthalandione
- Phthalic anhydride