{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:57:33Z","timestamp":1792450653947,"version":"4.5.0"},"reference-count":9,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T00:00:00Z","timestamp":1460419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>Determination of test material-induced cutaneous phototoxicity for risk assessment has traditionally been based on visually observed skin reactions such as erythema, edema, and flaking. Because of its role in determining a toxic effect, the use of histopathological evaluation in this determination arises from time to time. However, there is little published information regarding the time course and types of histopathologic changes in the skin after test material-induced phototoxic insult nor any regulatory requirement or precedent for its use. This work evaluated both the visual and histopathological time course of the phototoxic response of the skin of the Long-Evans rat after oral administration of the phototoxins sparfloxacin and 8-methoxypsoralen (MOP) followed by a single exposure to solar-simulated ultraviolet radiation. Both sparfloxacin and 8-MOP elicited visual cutaneous reactions and microscopic changes consistent with a phototoxic response. The visually observed cutaneous time course and elicited histopathologic changes differed in response and extent for each phototoxin, but in both instances, microscopic evaluation did not alter the determination of a phototoxic response based on visual observations. These results indicate that, though histopathologic evaluations may have value for investigating mechanisms of phototoxicity, histopathologic evaluation of the skin is not warranted for determination of phototoxic potential in safety assessment intended for regulatory submission.<\/jats:p>","DOI":"10.1177\/0192623316643617","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T22:00:01Z","timestamp":1460498401000},"page":"545-551","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Cutaneous Phototoxicity"],"prefix":"10.1177","volume":"44","author":[{"given":"Douglas B.","family":"Learn","sequence":"first","affiliation":[{"name":"Charles River Laboratories, Horsham, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle W.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Horsham, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,4,12]]},"reference":[{"key":"bibr1-0192623316643617","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2003.05582.x"},{"key":"bibr2-0192623316643617","unstructured":"Dougherty M. E., Baker J. F., Brown M., Learn D. B. (2013). \u201cPreclinical phototoxicity assays: Internal validation using known human phototoxins.\u201d Poster presented at the 15th Congress of the European Society for Photobiology meeting, Liege, Belgium."},{"key":"bibr3-0192623316643617","unstructured":"European Agency for the Evaluation of Medicinal Products. (2002). Note for guidance on photosafety testing. Committee for Proprietary Medicinal Products. CPMP\/SWP\/398\/01. June 27, 2002."},{"key":"bibr4-0192623316643617","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(99)00010-9"},{"key":"bibr8-0192623316643617","doi-asserted-by":"publisher","DOI":"10.1016\/0278-6915(84)90133-9"},{"key":"bibr9-0192623316643617","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration. (2003). \u201cThe guidance on photosafety testing\u201d. United States Federal Register vol. 68, no. 88 FR Doc. 03\u201311216, Docket No. 99D\u20135435, p. 24487."},{"key":"bibr5-0192623316643617","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration. Notice. (2010a). \u201cGuidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3(R2). Note for guidance on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. Step 5.\u201d United States Federal Register vol. 75, no. 13, Docket No. FDA\/2008\/D\/0470, p. 3471, January 21, 2010."},{"key":"bibr7-0192623316643617","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration. Notice. (2010b). \u201cNonclinical evaluation for anticancer pharmaceuticals. S9. Step 5.\u201d Federal Register, March 8, 2010, vol. 75, no. 44. Docket No. FDA\/2009\/D\/0006, p. 10487."},{"key":"bibr6-0192623316643617","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration. Notice. (2015). \u201cPhotosafety evaluation of pharmaceuticals. S10. Step 5.\u201d United States Federal Register, March 26, 2015, vol. 80, no. 17. Docket No. FDA\/2013\/D\/0068, pp. 4282\u201383."}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623316643617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623316643617","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623316643617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:37:54Z","timestamp":1777653474000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623316643617"}},"subtitle":["Clinical Observations versus Histopathological Findings"],"short-title":[],"issued":{"date-parts":[[2016,4,12]]},"references-count":9,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1177\/0192623316643617"],"URL":"https:\/\/doi.org\/10.1177\/0192623316643617","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,12]]}}}