Phototoxicity is a relatively common phenomenon and is an adverse effect of some systemic drugs. The fundamental initial step of photochemical reactivity is absorption of a photon; however, little guidance has been provided thus far regarding how ultraviolet-visible (UV-vis) light absorption spectra may be used to inform
testing strategies for investigational drugs. Here we report the results of an inter-laboratory study comparing the data from harmonized UV-vis light absorption spectra obtained in methanol with data from the
in vitro 3T3 Neutral Red Uptake Phototoxicity Test. Six pharmaceutical companies submitted data according to p
redefined quality criteria for 76 compounds covering a wide range of chemical classes showing a diverse but 鈥減ositive鈥?enhanced distribution of photo irritation factors (22%: PIF < 2, 12%: PIF 2-5, 66%: PIF > 5). For compounds being formally positive (PIF value above 5) the lowest reported molar extinction coefficient (MEC) was 1700 L mol
鈭? cm
鈭? in methanol. However, the majority of these formally positive compounds showed MEC values being significantly higher (up to almost 40,000 L mol
鈭? cm
鈭?).
In conclusion, an MEC value of 1000 L mol鈭? cm鈭? may represent a reasonable and pragmatic threshold warranting further experimental photosafety evaluation.