TOXICITY Mice and rats experienced swelling and darkening of exposed tissue at single dosages of >0.85 mg/kg under normal lighting [L1128]. Systemic toxicity presented as reduced red blood cell and platelet counts and increased white blood cell counts and liver and spleen weights. Skin inflammation, pycnotic spermatocytes and increased extramedullary haematopoiesis in spleen and the lymph nodes was also observed. Under low-light conditions mild phototoxicity was observed only at high doses.; ; Severe phototoxicity has been seen in rats with repeated doses of up to 1 mg/kg/day under normal lighting [L1128]. This effect is less severe under low-light conditions. Two weeks of repeated doses of 0.5-0.6 mg/kg/day resulted in inflammation of the injection site and skin in rats. At 0.3 mg/kg/day under low-light in rats, the only effect seen was an increase in white blood cell counts.; ; In beagle dogs recieving repeated doses of up to 3mg/kg/day under low-light conditions, reddening of the skin and injection site inflammation was seen [L1128]. Serious injection site damage was observed.

MOA Temoporfin is excited from ground state to the first excited singlet state by the application of 652 nm light [L1128, A31547]. It is then thought to undergo intersystem crossing to an excited triplet state which is longer lived and able to interact with surrounding molecules [A31547]. It is then thought to produce cytotoxic species by either a Type I or Type II reaction typical of agents used in photodynamic therapy. Type I involves either hydrogen abstraction of electron transfer from the excited photosensitizer to a substrate molecule to produce free radicals or radical ions. Type II reactions involve a similar reaction with oxygen as the substrate to produce reactive oxygen species. These reactive products cause oxidative damage to the cancer cell resulting in cell death.; ; There is evidence that photodynamic therapy with Temoporfin activates macrophages and increases phagocytosis [A31548]. These activated macrophages also produce more tumour necrosis factor-α (TNF-α) and nitric oxide (NO). It is thought that this increase in macrophage activity contributes to the efficacy of therapy through phagocytosis of cancer cells and increased cell death signalling though TNF-α. The increase in NO production likely contributes to oxidative damage through reactive nitrogen species.