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EC number: 201-898-9 | CAS number: 89-32-7
Carcinogenicity
Administrative data
Description of key information
An EPA OPPTS 870.430 study was conducted using phthalic anhydride, an analogue substance for PMDA, by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered phthalic anhydride at one of two doses, either 7,500 or 15,000 ppm, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical.
Groups of 50 mice of each sex were administered the test chemical at one of two doses, initially either 25,000 or 50,000 ppm, for 32 weeks. Because of excessive depressions in the amount of body weight gained in the dosed groups, the doses for the males were then reduced to 12,500 and 25,000 ppm, respectively, and the doses for the females were reduced to 6,250 and 12,500 ppm. Administration of the test chemical at the lowered doses was continued for 72 weeks. All surviving mice were killed at the end of the period of administration of the test chemical. Mean body weights of the high-dose male rats and of the low- and high-dose mice of each sex were lower than those of the corresponding controls; mean body weights of the low-dose male rats and of both the low- and high-dose female rats were essentially unaffected by administration of the test chemical. Depressions in the amount of body weight gained in the male and female mice were dose related throughout the bioassay. Survivals of the rats and mice were not affected by administration of the test chemical.
No tumors occurred in the rats or mice of either sex at incidences that could be clearly related to the administration of the test chemical.
Rats: LOAEL = 15,000 ppm (1000 mg mg/kg bw/day) based on reduced body weight gain (males); NOAEL = 7500 ppm (500 mg/kg bw/day); no conclusive evidence for carcinogenicity in this bioassay.
Mice: LOAEL (males) = 16,346 ppm (approx. 2340 mg/kg bw/day) and NOAEL (males) = Not established; LOAEL (females) = 12,019 ppm (approx. 1717 mg/kg bw/day ) and NOAEL (females) = Not established.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Remarks:
- Analog substance
- Adequacy of study:
- key study
- Study period:
- 1979
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Analogue substance. Well documented study from Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014, USA
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.4300 (Combined Chronic Toxicity / Carcinogenicity)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Phthalic anhydride
- Species:
- other: Rat and Mouse
- Strain:
- other: Male and female F344 rats and B6C3F1 mice
- Remarks:
- See attached report
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- See attached report
- Route of administration:
- oral: feed
- Vehicle:
- not specified
- Remarks:
- See attached report
- Details on exposure:
- Via diet for 105 weeks for rats and 32 or 72 weeks for mice.
- Analytical verification of doses or concentrations:
- not specified
- Remarks:
- See attached report
- Details on analytical verification of doses or concentrations:
- See attached report
- Duration of treatment / exposure:
- Via diet for 105 weeks for rats and 32 or 72 weeks for mice.
- Frequency of treatment:
- Daily in diet
- Dose / conc.:
- 7 500 ppm (nominal)
- Remarks:
- Rats
- Dose / conc.:
- 15 000 ppm (nominal)
- Remarks:
- Rats
- Dose / conc.:
- 6 250 ppm (nominal)
- Remarks:
- Mice
- Dose / conc.:
- 12 500 ppm (nominal)
- Remarks:
- Mice
- Dose / conc.:
- 25 000 ppm (nominal)
- Remarks:
- Mice
- No. of animals per sex per dose:
- 50
- Control animals:
- not specified
- Details on study design:
- See attached report
- Positive control:
- No
- Observations and examinations performed and frequency:
- See attached report
- Sacrifice and pathology:
- See attached report
- Other examinations:
- See attached report
- Statistics:
- See attached report
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- See attached report
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- See attached report; as expected in the aging rat or mouse
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- See attached report; impaired body weights in both species.
- Food consumption and compound intake (if feeding study):
- not specified
- Description (incidence and severity):
- See attached report
- Food efficiency:
- not specified
- Description (incidence and severity):
- See attached report
- Water consumption and compound intake (if drinking water study):
- not specified
- Description (incidence and severity):
- See attached report
- Ophthalmological findings:
- not specified
- Description (incidence and severity):
- See attached report
- Haematological findings:
- not specified
- Description (incidence and severity):
- See attached report
- Clinical biochemistry findings:
- not specified
- Description (incidence and severity):
- See attached report
- Urinalysis findings:
- not specified
- Description (incidence and severity):
- See attached report
- Behaviour (functional findings):
- not specified
- Description (incidence and severity):
- See attached report
- Immunological findings:
- not specified
- Description (incidence and severity):
- See attached report
- Organ weight findings including organ / body weight ratios:
- not specified
- Description (incidence and severity):
- See attached report
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- See attached report
- Neuropathological findings:
- not specified
- Description (incidence and severity):
- See attached report
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- See attached report; no abnormalities
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- See attached report; no neoplasms
- Other effects:
- not specified
- Description (incidence and severity):
- See attached report
- Details on results:
- See attached report
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Rats
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Rats
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 2 340 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Mice
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 1 717 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Mice
- Critical effects observed:
- no
- Conclusions:
- It is concluded that under the conditions of this bioassay that phthalic anhydride was not carcinogenic for F344 rats or B6C3F1 mice of either sex.
- Executive summary:
A bioassay of phthalic anhydride for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered phthalic anhydride at one of two doses, either 7,500 or 15,000 ppm, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical.
Groups of 50 mice of each sex were administered the test chemical at one of two doses, initially either 25,000 or 50,000 ppm, for 32 weeks. Because of excessive depressions in the amount of body weight gained in the dosed groups, the doses for the males were then reduced to 12,500 and 25,000 ppm, respectively, and the doses for the females were reduced to 6,250 and 12,500 ppm. Administration of the test chemical at the lowered doses was continued for 72 weeks. The time-weighted average doses for the males were either 16,346 or 32,692 ppm, and those for the females were either 12,019 or 24,038 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of the period of administration of the test chemical. Mean body weights of the high-dose male rats and of the low- and high-dose mice of each sex were lower than those of the corresponding controls; mean body weights of the low-dose male rats and of both the low- and high-dose female rats were essentially unaffected by administration of the test chemical. Depressions in the amount of body weight gained in the male and female mice were dose related throughout the bioassay. Survivals of the rats and mice were not affected by administration of the test chemical.
No tumors occurred in the rats or mice of either sex at incidences that could be clearly related to the administration of the test chemical.
Rats: LOAEL = 15,000 ppm (1000 mg mg/kg bw/day) based on reduced body weight gain (males); NOAEL = 7500 ppm (500 mg/kg bw/day); no conclusive evidence for carcinogenicity in this bioassay.
Mice: LOAEL (males) = 16,346 ppm (approx. 2340 mg/kg bw/day) and NOAEL (males) = Not established; LOAEL (females) = 12,019 ppm (approx. 1717 mg/kg bw/day ) and NOAEL (females) = Not established.
It is concluded that under the conditions of this bioassay that phthalic anhydride was not carcinogenic for F344 rats or B6C3F1 mice of either sex.
- Endpoint:
- carcinogenicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Rats
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Rats
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 2 340 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- other: Mice
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 1 717 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: Mice
Referenceopen allclose all
See attached report
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- other: Rats and mice: NOAEL for rats given
- Quality of whole database:
- Reliability 1
- System:
- other: body weights
- Organ:
- other:
Justification for classification or non-classification
Based on the data available the substance is not classified or labelled according to Regulation 1272/2008/EC (CLP).
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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