Registration Dossier

Administrative data

Description of key information

Based upon the outcome of a read across approach GSK2609973A is not expected to be cacinogenic. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A package of occupational toxicology tests and pharmacological screening assays have been completed for GSK2609973A. Functional receptor screening tests have also been conducting with this compound in order to understand its potential for interaction with the human glucocorticoid receptor.

The conclusion of the assessment relies primarily upon read across from structurally-related substances with the package of occupational toxicology tests providing data to support this approach. This is consistent with international guidelines for read across of toxicological data (1, 2).

1.   European Chemicals Agency, Guidance on information requirements and chemical safety assessment 1. Chapter R.6: QSARs and grouping of chemicals, Guidance for the Implementation of REACH.May 2008

2.   OECD, Series on Testing and Assessment, Number 80, Guidance on Grouping of Chemicals, September 2007


Justification for selection of carcinogenicity via oral route endpoint:
Not expected to be carcinogenic.
• Only a limited number of glucocorticoids have been tested for carcinogenicity, but some have produced an increase in hepatocullular tumours when tested via the oral route. This is thought to be due to exaggerated pharmacological activity at high doses that are probably not relevant to occupational exposure. The lack of corticosteroidal activity with GSK2609973A would suggest that these effects were also not of relevance to this substance.
• A single study reports an increase incidence of rare bone tumours in Sprague Dawley rats following two years dietary dosing at 0.25 mg/kg/day with Deflazacort, but this was not seen in a parallel study in mice.
• Available studies for fluticasone propionate and fluticasone furoate, two potent steroids, conducted via the inhalation route were negative.
• No alerts for carcinogenicity were obtained using DEREK, Lhasa, Leeds, UK.
• Alerts for DNA reactivity were obtained using the OECD QSAR Toolbox, mainly based around the epoxide moiety. However, it was not possible to produce a prediction of a test outcome due to limitations of the available data on existing steroids in the databases used by the application.

Justification for classification or non-classification

Taking account of the small package of studies with GSK2609973A and close structural similarity to substances for which a more complete dataset exists, it is considered justified to use a read-across approach to address any outstanding data-gaps for this material. 

Only a limited number of glucocorticoids have been tested for carcinogenicity, but some have produced an increase in hepatocellular tumours when tested via the oral route. This is considered to be a consequence of pharmacological activity at high doses for a prolonged period and probably not of relevance to typical occupational exposure. A single study reports an increase incidence of rare bone tumours in Sprague Dawley rats following two years dietary dosing at 0.25 mg/kg/day with Deflazacort, but this was not seen in a parallel study in mice. Studies conducted via the inhalation route with the potent glucocorticoids fluticasone propionate and fluticasone furoate were negative for tumourigenic effect. 

Based upon the outcome of this read across approach GSK2609973A is not expected to be cacinogenic.