MOBILE VIEW  | 

PHTHALIC ACID

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Phthalic acid is 1,2-benzenedicarboxylic acid. This agent received research attention in teratology because of structural similarities to thalidomide. Phthalic acid is used in the synthesis of dyes and dyestuffs, in medicines and perfumes, phenolphthalein, phthalimide, and anthranilic acid.

Specific Substances

    1) 1,2-Benezenedicarboxylic acid
    2) Benzene-1,2-dicarboxylic acid
    3) O-benzenedicarboxylic acid
    4) O-dicarboxy benzene
    5) O-phthalic acid
    6) CAS 88-99-3
    7) ACIDE PHTALIQUE (FRENCH)
    8) ANAZOL

Available Forms Sources

    A) FORMS
    1) Phthalic acid is a crystalline solid (Lewis, 1996; RTECS , 1999).
    B) USES
    1) Phthalic acid is used in synthesis of dyes and dyestuffs, in medicines and perfumes, phenolphthalein, phthalmide, and anthranilic acid (Lewis, 1996).
    2) Phthalic acid esters have also been used as plasticizers in many products (Bauer & Herrmann, 1997; Magill-Cuerden, 1996).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) No data are available about possible systemic effects of phthalic acid ingestion. Irritation of eyes, mucous membranes, and skin have been reported.
    0.2.4) HEENT
    A) CONJUNCTIVITIS - Eye irritation may occur.
    B) BLOODY NASAL DISCHARGE - Atrophy of the nasal mucosa or a bloody nasal discharge may occur.
    C) HOARSENESS - Cough and hoarseness have occurred in workers exposed to vapors.
    0.2.14) DERMATOLOGIC
    A) Phthalic acid is moderately irritating to skin.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) In individuals occupationally exposed to phthalic anhydride, urinary phthalic acid excretion was found to correlate significantly with workplace air levels of the anhydride (Pfaffli, 1986).

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis is NOT recommended.
    B) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) The minimum lethal and maximum tolerated human exposures are not known.

Summary Of Exposure

    A) No data are available about possible systemic effects of phthalic acid ingestion. Irritation of eyes, mucous membranes, and skin have been reported.

Heent

    3.4.1) SUMMARY
    A) CONJUNCTIVITIS - Eye irritation may occur.
    B) BLOODY NASAL DISCHARGE - Atrophy of the nasal mucosa or a bloody nasal discharge may occur.
    C) HOARSENESS - Cough and hoarseness have occurred in workers exposed to vapors.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Eye irritation has been noted in workers exposed to mixed vapors of phthalic acid and phthalic acid anhydride (ILO, 1983).
    3.4.5) NOSE
    A) BLOODY NASAL DISCHARGE - Nasal mucosal atrophy and a bloody nasal discharge have been noted in workers (ILO, 1983).
    3.4.6) THROAT
    A) HOARSENESS - Cough and hoarseness have been noted in workers exposed to mixed vapors (ILO, 1983).

Respiratory

    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CYANOSIS
    a) Cyanosis was noted in mice given 550 mg/kg intraperitoneally (RTECS , 1999).

Dermatologic

    3.14.1) SUMMARY
    A) Phthalic acid is moderately irritating to skin.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Phthalic acid is moderately irritating to skin and mucous membranes (Lewis, 1996).

Musculoskeletal

    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPERTONIA
    a) MICE - Muscle spasticity or muscle contractions have been reported in mice given phthalic acid at 550 mg/kg by the intraperitoneal route (RTECS , 1999).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) ANIMAL STUDY - In rat studies, there was no evidence of teratogenesis in fetuses exposed to phthalic acid (Ema et al, 1997).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS88-99-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) Germ cell mutagenicity was observed in mice (Jha et al, 1998). In adult male mice, exposure to phthalic acid resulted in induction of dominant lethal mutations and abnormal sperm heads.

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) In individuals occupationally exposed to phthalic anhydride, urinary phthalic acid excretion was found to correlate significantly with workplace air levels of the anhydride (Pfaffli, 1986).

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) In individuals occupationally exposed to phthalic anhydride, urinary phthalic acid excretion was found to correlate significantly with workplace air levels of the anhydride (Pfaffli, 1986).

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) DILUTION -
    1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
    3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
    4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
    5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).
    B) EMESIS/ NOT RECOMMENDED -
    1) Emesis is not recommended because the irritant potential outweighs the risk of systemic effects resulting from ingestion.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Emesis is NOT recommended. The irritant potential currently outweighs the risk of systemic effects.
    B) DILUTION
    1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
    3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
    4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
    5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) AIRWAY MANAGEMENT
    1) Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Summary

    A) The minimum lethal and maximum tolerated human exposures are not known.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human exposure is not known.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure is not known.

Workplace Standards

    A) ACGIH TLV Values for CAS88-99-3 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS88-99-3 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS88-99-3 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS88-99-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Reference: RTECS, 1999
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 550 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 2530 mg/kg

Toxicologic Mechanism

    A) Phthalic acid is directly irritating to skin and mucous membranes (Lewis, 1996). It is moderately toxic by ingestion and intraperitoneal route.

Physical Characteristics

    A) Phthalic acid is a crystalline solid (Lewis, 1996).
    B) colorless crystals (Lewis, 1996)

Molecular Weight

    A) 166.14 (Lewis, 1996)

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