Cancer Risk Assessment

Restylane gel contains 1,4-butanediol diglycidyl ether (BDDE), a compound that
has been shown to be mutagenic in various assay systems and may have been
associated with tumor formation in mice following topical application in one study.
Consequently, it is prudent to assess the potential carcinogenic risk of BDDE in
patients who receive injections of Restylane gel. The excess cancer risk in
humans was determined using two approaches: 1) simple linear extrapolation of
the dose associated with 10-6 risk from the tumor incidence at the lowest dose of
BDDE that produced an increased tumor incidence in the mouse study, with
conversion of this dose to a human equivalent dose; and 2) use of doseresponse
models to estimate the 10% tumor incidence, with subsequent
application of uncertainty factors to estimate the dose associated with 10-6 risk in
humans. The human equivalent doses associated with 10-6 excess cancer risk
derived using either approach were then compared to the dose of BDDE
estimated to be received by patients treated with Restylane.