Reaction mass of divinylbenzene and ethylstyrene

Carcinogenicity

Description of key information

2-year inhalation studies in rats and mice conducted under GLP and equivalent to OECD guideline 453 are available for DVB-HP.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

532 mg/m³

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The conclusion reached from the NTP study is that there was no evidence of carcinogenic activity in male mice and equivocal evidence of carcinogenic activity of DVB-HP in female mice based on the incidences of alveolar/bronchiolar adenoma or carcinoma in the lung, not reaching statistical significance. There was equivocal evidence of carcinogenic activity of DVB-HP in male rats based upon the occurrence of carcinomas in the kidney and glial tumors in the brain, not reaching statistical significance. There was no evidence of carcinogenic activity of DVB-HP in female rats. Based on these conclusions no classification for carcinogenicity is justified for any grade of the reaction mass of divinylbenzene and ethylstyrene according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information

Within an NTP bioassay test program, mice were exposed to DVB-HP via inhalation at concentrations of 0, 10, 30, or 100 ppm for 6 hours a day, 5 days per week for up to 105 weeks. Survival for all exposed groups of male and female mice was similar to that of the chamber controls. Mean body weights for 100 ppm males and for 30 and 100 ppm females were reduced relative to chamber controls. The incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in 100 ppm males were greater than chamber control incidences, but the incidences of adenoma or carcinoma (combined) were within the historical control range. The incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in all exposed groups of females were generally greater that those in the chamber controls; the incidences were at the upper end or exceeded the historical control ranges, but were not statistically significant. There was a greater incidence and severity of alveolar epithelial hyperplasia in 100 ppm females and a greater severity of this lesion in 30 ppm females, when compared to chamber controls. The incidences and/or severities of atypical bronchiole hyperplasia were significantly increased in all exposed groups of mice. Nonneoplastic nasal lesions occurred in most DVB-exposed mice. The chronic, non-neoplastic LOEL for mice was 10 ppm DVB-HP, based on non-neoplastic nasal lesions. The conclusion reached from the NTP study is that there was no evidence of carcinogenic activity in male mice and equivocal evidence of carcinogenic activity of DVB-HP in female mice based on the incidences of alveolar/bronchiolar adenoma or carcinoma in the lung, not reaching statistical significance.

Rats were exposed to DVB-HP via inhalation at concentrations of 100, 200, or 400 ppm for 6 hours a day, 5 days per week for up to 105 weeks. Survival of 400 ppm females was significantly less than that of the chamber control group. Mean body weights of 400 ppm males and females were significantly less than those of the controls during the second half of the study. Renal tubule carcinomas occurred in two of 50 males exposed to 400 ppm in the original kidney sections, an incidence that exceeded the historical control range. In 400 ppm males, the incidence of renal tubule hyperplasia was increased, and the incidence of nephropathy was significantly increased. Following combined analysis of single and step-section data, the incidences of renal tubule adenoma and adenoma or carcinoma (combined) were marginally greater in 200 and 400 ppm males, and the incidence of renal tubule hyperplasia was significantly increased in 400 ppm males. The incidences of malignant glial cell tumours (malignant astrocytoma and oligodendroglioma) in the brain were slightly increased in 100 and 200 ppm males, and the incidence in the 200 ppm group exceeded the historical range for chamber controls, but were not statistically significant. There were increased incidences of degenerative and regenerative changes in the olfactory epithelium in the nose of all exposed groups of rats. The incidence of focal chronic inflammation in the lung of 400 ppm males was significantly greater than in the chamber control group. The chronic non-neoplastic LOEL for rats was 100 ppm DVB-HP, based on non-neoplastic nasal effects. The conclusion reached from the NTP study is that there was equivocal evidence of carcinogenic activity of DVB-HP in male rats based upon the occurrence of carcinomas in the kidney and glial tumors in the brain, not reaching statistical significance. There was no evidence of carcinogenic activity of DVB-HP in female rats.

The relevance of the nasal effects observed in both species is discussed extensively in section 7.5 of IUCLID. According to this assessment the nasal effects caused by inhalation exposure to DVB are comparable to the effects caused by inhalation exposure to styrene. In addition, it was shown that the major routes of DVB hepatic metabolism are comparable to styrene and it is expected that the routes of non-hepatic metabolism of DVB would also be consistent with those observed for styrene. Therefore, it is concluded that the nasal effects observed in mice and rats after inhalation exposure to DVB are not relevant for human exposure to DVB.