Diphenyl carbonate

Carcinogenicity

Description of key information

Old and limited studies in B6C3F1 and B6AKF1 mice with oral dosing (3 weeks oral gavage followed by oral feeding) of 100 mg/kg bw/day diphenyl carbonate for 18 months showed no increase in tumor incidences (Bionetics, 1968).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Of the four supporting studies, two were awarded a reliability score of 2 in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997) and two were awarded a reliability score of 3. The overall quality of the database is therefore considered to be adequate.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to carcinogenicity.

Additional information

In accordance with Section 8.9.1 of Column 2 of REACH Annex X, it is considered justified to omit the carcinogenicity study on the grounds that the substance does not have a widespread dispersive use and there is no evidence of frequent or long-term human exposure. Furthermore, the substance has shown no evidence of potential to cause germ cell mutagenicity nor is there evidence from the repeated dose study that the substance is able to induce hyperplasia and/or pre-neoplastic lesions.

 

Supporting Information

There are four supporting study summaries to address this endpoint. The work was carried out prior to the inception of GLP and no guidelines were followed. Two were awarded a reliability score of 2 in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997), as there is limited documentation. Two were awarded a reliability score of 3 due to an unsuitable test system. All 4 were summarised from the same report (Bionetics, 1968).

 

The first and second supporting study summaries were both performed in male and female mice; the first endpoint summarises the effects in (C57BL/6 X AKR)F1 mice and the second summarises the effects in (C57BL/6 X C3H/Anf)F1 mice. Identical methodology was used for both strains and identical results were obtained.

A carcinogenicity study was carried out with 130 chemicals and 7 positive controls. The test material was administered at 100 mg/kg (18 animals per sex) via gavage in 0.5 % gelatin for the first 3 weeks of the study, followed by oral feeding. The test material was mixed directly with the diet, which was provided ad libitum. The same concentration (approximately the maximal tolerated dose) was maintained throughout the 18 month administration period. Administration of the test material began when the mice were 7 days of age.

The postmortem procedure included an external examination and a thorough examination of thoracic and abdominal cavities, with histologic examination of major organs and of all grossly visible lesions. Mortality-related observations included no treatment related differences; tumour incidences were not affected by the test material (only limited information). Necropsy findings included no significant findings as compared to untreated and vehicle controls whereas clinical signs observed were not reported. The administration of the positive control substances resulted in the expected increases in tumour incidence.

 

The third and fourth supporting study summaries were both performed in male and female mice; the third endpoint summarises the effects in (C57BL/6 X C3H/Anf)F1 mice and the fourth summarises the effects in (C57BL/6 X AKR)F1 mice. Identical methodology was used for both strains and identical results were obtained.

A carcinogenicity study was carried out with 130 chemicals. The test material was administered as a single subcutaneous injection into the nape of the neck of 18 animals per sex at a dose of 1000 mg/kg when the animals were 28 days of age. The test material was dosed as a suspension in DMSO at an application volume of 0.05 mL. The MTD was determined in a preliminary acute toxicity study. The animals were observed for 18 months.

No treatment related differences were observed; tumour incidences were not affected by the test material, however, there is only limited information available.