Reaction mass of 4,4'-isopropylidenediphenol and phenol

Carcinogenicity

Description of key information

The reaction mass of phenol and 4,4'-isopropylidenediphenol (BPA) contains phenol and BPA. 
Phenol is not considered to be a carcinogen in experimental animals after repeated oral exposure (compare also with EU-RAR, 2006). 
BPA: A dietary carcinogenicity study in rats and mice concluded that BPA was not carcinogenic in either species because the tumour findings were not considered toxicologically significant.

Justification for classification or non-classification

No classification warranted for the reaction mass, as none of the constituents poses any concern of carcinogenicity.

Additional information

For considerations on the analogue approach used please refer to the reporting form attached to section 13 of the IUCLID.

PHENOL:

This endpoint is presented in Section 4.1.2.8 of the EU-RAR (2006; page 126). In the EU-RAR it was concluded that phenol is considered not to be a carcinogen in animals. 

Phenol Long-term oral studies in mice and rats (NIH, 1980)

Male and female B6C3F1 mice were exposed to 0, 2500 or 5000 ppm phenol in the drinking water (ca. 280 and 370 mg/kg bw/day). In low and high dose groups the body weight was reduced and water consumption was suppressed to 75% and 50-60% of control value, respectively. Histopathology revealed no treatment related non-neoplastic and neoplastic. Phenol was not toxic or carcinogenic for male or female B6C3F1 mice.

Male and female F344 rats exposed to the same concentrations in the drinking water ingested ca. 200 and 450 mg/kg bw/day, respectively. In both treatment groups the water consumption was decreased (80% and 90% of control value, respectively) and in the high dose groups the body weight was reduced. No treatment related effects were detected in histopathological evaluation of non-neoplastic effects. The incidence of leukaemia or lymphomas, adrenal pheochromocytomas, thyroid c-cell carcinomas (not significant when combined with c-cell adenomas), and interstitiell cell tumours of the testes (high spontaneous rate) was significantly increased only in male rats that received 2,500 ppm phenol, no such effect could be observed in the high dose males. The lack of increased tumour incidences in the high dose group and the statistical analyses indicate that the increased neoplastic incidences in males of the low dose group is not considered by the authors to be associated with the administration of phenol. No increased tumour incidences were found in female rats. It is concluded that phenol was not carcinogenic for male or female F344 rats.

BPA:

The 2003 EU RAR concluded that there are no human data contributing to the assessment of whether or not BPA is carcinogenic, but a dietary carcinogenicity study in rats and mice concluded that BPA was not carcinogenic in either species because the tumour findings were not considered toxicologically significant. No inhalation or dermal carcinogenicity studies were available, although in repeat exposure inhalation toxicity studies, BPA did not exhibit properties that raised concern for potential carcinogenicity. Taking into account all the animal data available, it was concluded that the animal evidence suggests that BPA does not have carcinogenic potential.

The 2008 updated EU RAR concluded that the new information on the potential carcinogenic and/or promoting effects of BPA in prenatal and neonatal rat models supports the original conclusion that BPA does not possess any significant carcinogenic potential. This is based on one new study in which the full carcinogenic potential of BPA on the mammary gland was examined in a prenatal model. This study claimed that BPA induced preneoplastic and neoplastic lesions of the mammary gland, but its validity was hampered by serious methodological limitations and its findings are inconsistent with the absence of preneoplastic lesions of the mammary gland in the offspring from several standard multi-generation studies in rats and mice. Other new studies suggest that prenatal or neonatal exposure to BPA does not exert promoting activity on the carcinogenesis induced by established carcinogens/initiators in specific organs.

There is no significant new information on the carcinogenicity of BPA that was not discussed in the 2003 or 2008 EU RARs.