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Toxicological information

Carcinogenicity

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Description of key information

Data indicate that the chronic administration of terephthalic acid at high concentrations results in the formation of urinary bladder tumours as a consequence of chronic inflammation secondary to calculi formation.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Evidence of carcinogenicity was seen in a chronic rat study (Preache, 1983; Ackerman, 1983) in which female rats had an increased incidence of transitional cell adenomas and carcinomas at the highest dietary concentration equivalent to approximately 1000 mg/kg bw/d. Findings were secondary to urolithiasis and were associated with inflammation and irritation. Similar findings in the bladder were reported in the study of Gross (1974), in which bladder tumour incidences were increased at dietary dose levels of 2% and 5% (equivalent to approximately 1000 mg/kg bw/d and 2500 mg/kg bw/d, respectively). Data therefore indicate that chronic exposure to a very high level of terephthalic acid in the diet results in bladder carcinogenicity as a consequence of urolith formation and consequent irritation and inflammation of the urothelium. The mechanism of carcinogenicity is therefore non-genotoxic, has a clearly identified threshold and is of little relevance to the human risk assessment.


Justification for selection of carcinogenicity via oral route endpoint:
Guideline compliant study with some limitations but with supporting weight of evidence obtained from other studies

Carcinogenicity: via oral route (target organ): urogenital: urinary bladder

Justification for classification or non-classification

No classification is proposed for carcinogenicity. Increased incidences of urinary bladder transitional cell tumours were seen in two seperate rat studies at dose levels equivalent to 1000 mg/kg bw/d and higher. Findings are secondary to chronic irritation caused by urolithiasis as a consequence of the precipitation of the substance in the urine at high dose levels and are only seen where the limit of solubility of TPA in the urine is exceeded. Findings were only seen at dose levels that will not be encountered by humans following occupational exposure and, additionally, rats are known to be more susceptible to urolithiasis. TPA is non-genotoxic and the carcinogenicity seen in rats is a clear threshold effect associated with chronic mechanical irritation.