Phototoxicity

A number of in vitro models have been developed for assessing the phototoxic potential of chemicals. The most widely used in vitro phototoxicity assay is the in vitro 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT). This assay was validated by ECVAM and subsequently adopted by the Organization for Economic Co-operation Development (OECD) as Test Guideline (TG) 432 (OECD, 

TABLE 12.1 In Vitro Approaches to Assessment of Potential for Immune-Mediated Skin Effects 

In vitro 3D RhE model phototoxicity tests have been developed (Edwards et al., 1994). These assays also measure tissue viability after exposure to a chemical in the presence and absence of light. ECVAM sponsored a successful prevalidation of the EpiDerm Phototoxicity Test (EpiDerm PT) in three laboratories under blind sample conditions (Liebsch et al., 1999). A subsequent ECVAM-supported project demonstrated that the EpiDerm PT may also serve as a tool for the determination of phototoxic potency of topically applied phototoxins (Kanddrova et al., 2005 Kejlova et al., 2007). The EpiDerm PT is established in many laboratories of the cosmetic industry worldwide, and the protocol has been successfully adopted for other commercial epidermal models. 

Advantages of the EpiDerm PT over the 3T3 NRU PT are the 3D structure, the stratum comeum barrier, and the lipid profile that are similar to those of human epidermis. These features enable application of undiluted solid and liquid materials as well as testing of water-insoluble materials and UVB absorbing chemicals, conditions which are not possible in the 3T3 NRU PT assay due to the lack of barrier, inability of 3T3 cells to tolerate UVB and solubility issues. 

Options for collecting additional data in biological systems 

The optimal in vitro cutaneous model should possess viable cells and structures similar to intact skin as well as a functional vasculature. This would allow all 

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Thus, multiphoton excitation eliminates unwanted out-of-focus excitation, lumecessary phototoxity and bleaching. However, efficient power sources are required and, since the efficiency of multiphoton excitation is usually low, the times needed to generate unages are mcreased. 

Phototoxicity is negative for all oils except bergamot, expressed, for which it is severe. 

Irradiation of lomefloxacin 271 in dilute neutral aqueous solution (in which it exists as a zwitter ion) in Pyrex-filtered 500 W medium pressure mercury (Helios Italquartz) at 17°C gave pyrrolo[3,2,l-(/ ]quinoline 272 (99JOC5388). Under this condition, reductive defluorination via a radical anion took place. This study is important because of the phototoxicity of the fluorinated compounds which could be used as antibacterials (Scheme 49). 

A number of quinolones had to be taken off the market due to toxic effects on the liver, heart, or other organs, that became recognized only after marketing (e.g. temafloxacin, trovafloxacin, grepafloxacin). A risk for severe cardiotoxicity, hepatotoxicity, or phototoxicity is... 

The combination of methotrexate and UVB seems to be synergistic responses may occur with lower cumulative doses of both methotrexate and UVB. However, stopping methotrexate may cause rebound21,33 and there is some concern about photosensitivity.21 Methotrexate and PUVA have been used together in patients refractory to other treatments however, there is additive carcinogenesis (especially increasing the risk of squamous cell cancer) and subacute phototoxicity.21... 

Adverse effects with the tetracyclines include gastrointestinal upset drug interactions with dairy products, antacids, and iron and phototoxicity. Minocycline can also cause vestibular complications (headache and dizziness) and skin discoloration that is not typical with tetracycline and doxycycline.16... 

Tetracycline Tablets, capsules 250, 500 mg 500 mg twice daily before meals Maintenance dose 500 mg daily Gl upset, phototoxicity, tooth discoloration, drug and food interactions... 

Phototoxicity caused by drugs is a problem that is being observed with greater frequency. The primary... 

Bohm, F, Edge, R, Foley, S, Lange, L, and Truscott, TG, 2001. Antioxidant inhibition of porphyrin-induced cellular phototoxicity. J Photochem Photobiol B 65, 177-183. 

Rozanowski, B, Cuenco, J, Davies, S, Shamsi, FA, Zadlo, A, Dayhaw-Barker, P, Rozanowska, M, Sarna, T, and Boulton, ME, 2008c. The phototoxicity of aged human retinal melanosomes. Photochem Photobiol 84, 650-657. 

Keywords Dual-wavelength ratiometry Electrochromism Ion-transporting membrane proteins Membrane dipole potential Phototoxicity... 

Bioassays of a considerable number of drugs embodying a combination of porphyrin and cis-platin moieties in the same molecule have led to compound (43) in vitro and in vivo studies on this compound showed a phototoxicity which was additive to the cytotoxic effect of the platinum moiety.190-193... 

The answer is c. (Hardman, pp 1134-1135.) Hematologic toxicity is by far the most important adverse effect of chloramphenicol The toxicity consists of two types (1) bone marrow depression (common) and (2) aplastic anemia (rare) Chloramphenicol can produce a potentially fatal toxic reaction, the gray baby syndrome, caused by diminished ability of neonates to conjugate chloramphenicol with resultant high serum concentrations. Tetracyclines produce staining of the teeth and phototoxicity... 

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