Phthalic anhydride [factsheet]

PHTHALIC ANHYDRIDE

Please Note: The main sources of information for this fact sheet are EPA's IRIS, which contains information on oral chronic toxicity of phthalic anhydride and the RfD, and the National Cancer Institute's Bioassay of Phthalic Anhydride for Possible Carcinogenicity. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* Exposure to phthalic anhydride may occur during the manufacture of phthalate-derived products. (1)

* It has been suggested that exposure to phthalic anhydride may occur from the use of plastics from which phthalate plasticizers are leached, specifically certain medical plastics such as blood bags, plastic syringes, and plastic tubing. (1)

* Phthalate esters have been identified as environmental pollutants. (1)

Assessing Personal Exposure

* There is no known medical test available to determine whether someone has been exposed to phthalic anhydride. (2)

Health Hazard Information

Acute Effects:

* Phthalic anhydride is irritating to the eyes, respiratory tract, and the skin in humans, but no permanent injury is observed. (2)

* Tests involving acute exposure of animals, such as the LD₅₀ test in rats, have shown phthalic anhydride to have moderate acute toxicity. (3)

Chronic Effects (Noncancer):

* Persons in factories manufacturing phthalic anhydride and phthalic acid have developed conjunctivitis and also irritation of the skin and of mucous membranes of the respiratory tract. The long-term (chronic) effects observed in workers exposed to phthalic anhydride were occasional bloody sputum, emphysema, some lowering of blood pressure, and minor signs of CNS excitation. (1,2)

* Animals exposed to heated phthalic anhydride experienced congestion, irritation, and injury of lung cells. (2)

* EPA has not established an RfC for phthalic anhydride. (4)

* EPA has calculated a provisional RfC of 0.12 mg/m³ for phthalic anhydride. (5)

* EPA has established an RfD of 2.0 mg/kg/d for phthalic anhydride based on lung and kidney histopathology in mice. (4)

* EPA has high confidence in the study on which the RfD is based because the study is a well-designed feeding study in two species that defines a no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL); medium confidence in the database because teratogenicity has not been tested adequately; and, consequently, medium confidence in the RfD because of the lack of reproductive toxicity data. (4)

Reproductive/Developmental Effects:

* Pertinent studies regarding reproductive or developmental effects in animals or humans were not available.

Cancer Risk:

* No studies were available on the carcinogenic effects of phthalic anhydride in humans.

* A bioassay of phthalic anhydride for possible carcinogenicity was conducted by administering phthalic anhydride in feed to groups of 50 rats and 50 mice of each sex. It was observed that no tumors occurred in the rats or mice of either sex at incidences that could be clearly related to the administration of phthalic anhydride. (1)

* The carcinogenicity assessment for lifetime exposure to phthalic anhydride is currently under review by EPA. (4)

Physical Properties

* Phthalic anhydride is a white (lustrous needles) solid. (6)

* Phthalic anhydride has an odor threshold of 0.053 ppm. (7)

* Phthalic anhydride is slightly soluble in water. (8)

* The chemical formula for phthalic anhydride is C₈H₄O₃, and it has a molecular weight of 148.12/mol. (3,6)

* The vapor pressure for phthalic anhydride is 5.14 H 10^-4 mm Hg at 25 EC. (9)

Uses

* Phthalic anhydride is an important chemical intermediate in the plastics industry from which are derived numerous phthalate esters that function as plasticizers in synthetic resins. Phthalic anhydride itself is used as a monomer for synthetic resins such as glyptal, the alkyd resins, and the polyester resins. (1)

* Phthalic anhydride is also used as a precursor of anthraquinone, phthalein, rhodamine, phthalocyanine, fluorescein, and xanthene dyes. (1)

* Phthalic anhydride is used in the synthesis of primary amines, the agricultural fungicide phaltan, and thalidomide. Other reactions with phthalic anhydride yield phenolphthalein, benzoic acid, phthalylsulfathiazole (an intestinal antimicrobial agent), and orthophthalic acid. (1)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
100.0
_ _ _ _ 10.0		* OSHA PEL, MSHA standard (12 mg/m³)	3
_ _ _ _ 1.0		* ACGIH TLV and OSHA PEL (final) (6 mg/m³)	3

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect.

MSHACMine Safety and Health Administration.

OSHA PEL FinalCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; final OSHA allowable level in workplace air averaged over an 8-h shift.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

References

1. National Cancer Institute. Bioassay of Phthalic Anhydride for Possible Carcinogenicity. Technical Report 159. U.S. Public Health Service, Bethesda, MD. 1979.

2. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Phthalic Anhydride. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

5. U.S. Environmental Protection Agency. Health Effects Assessment Summary Tables. Annual Update. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

6. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck & Co., Inc., Rahway, NJ. 1989.

7. J.E. Amoore and E. Hautala. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

8. R.C. Weast and M.J. Astle, Eds. CRC Handbook of Chemistry and Physics. 63rd ed. CRC Press, Inc., Boca Raton, FL. 1982.

9. U.S. Environmental Protection Agency. Assessment Tools for the Evaluation of Risk (ASTER, online database). Environmental Research Laboratory, Duluth, MN. 1993.