{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:21:53Z","timestamp":1790968913034,"version":"4.1.0"},"reference-count":52,"publisher":"Japanese Society of Toxicologic Pathology","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Toxicol Pathol"],"published-print":{"date-parts":[[2023]]},"DOI":"10.1293\/tox.2022-0103","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T22:10:22Z","timestamp":1672351822000},"page":"85-94","source":"Crossref","is-referenced-by-count":27,"title":["Morphological characteristics and notes of the skin in preclinical toxicity          assessment"],"prefix":"10.1293","volume":"36","author":[{"given":"Takayasu","family":"Moroki","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Co Ltd Tokushima Research              Institute, Drug Safety Research, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"121","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1.  Mecklenburg              L,                Kusewitt              D,                Kolly              C,                Treumann              S,                Adams              ET,                Diegel              K,                Yamate              J,                Kaufmann              W,                M\u00fcller              S,                Danilenko              D, and                Bradley              A.            Proliferative and non-proliferative lesions of the rat and mouse            integument. J Toxicol Pathol.            26(Suppl):            27S\u201357S. 2013.","DOI":"10.1293\/tox.26.27S"},{"key":"2","unstructured":"2.  Kierszenbaum              AL, and                Tres              LL. Chapter 11: Integumentary          system. In: Histology and Cell Biology: An Introduction to Pathology, 5th ed. Elsevier,          Philadelphia. 389\u2013416. 2020."},{"key":"3","unstructured":"3.OECD. OECD guideline for testing of chemicals          no. 404: Acute dermal irritation\/corrosion. 24. Apr. 2002."},{"key":"4","unstructured":"4.OECD. OECD guideline for testing of chemicals          no. 406: Skin sensitisation. 17. Jul 1992."},{"key":"5","unstructured":"5.OECD. OECD guideline for testing of chemicals          no. 429: Skin sensitization: local lymph node assay. 22 Jul 2010."},{"key":"6","doi-asserted-by":"crossref","unstructured":"6.  Mahl              JA,                Vogel              BE,                Court              M,                Kolopp              M,                Roman              D, and                Nogu\u00e9s              V. The minipig            in dermatotoxicology: methods and challenges. Exp Toxicol            Pathol. 57: 341\u2013345.            2006.","DOI":"10.1016\/j.etp.2006.03.004"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7.  Stricker-Krongrad              A,                Shoemake              CR,                Pereira              ME,                Gad              SC,                Brocksmith              D, and                Bouchard              GF. Miniature            swine breeds in toxicology and drug safety assessments: what to expect during clinical            and pathology evaluations. Toxicol Pathol.            44: 421\u2013427. 2016.","DOI":"10.1177\/0192623315613337"},{"key":"8","unstructured":"8.  Diegel              K,                Andrews-Jones              L,                Danilenko              DM, and                Aibo              DI. Skin Appendix 3:          Mini-atlas of organ system anatomy and histology. Organ system teams. In: The Illustrated          Dictionary of Toxicologic Pathology and Safety Science. PS Sahota, RH Spaet, P Bentley,          and ZW Wojcinski (eds). 585\u2013618. 2019."},{"key":"9","doi-asserted-by":"crossref","unstructured":"9.  Diegel              KL,                Danilenko              DM, and                Wojcinski              ZW. Chapter 55: Integument.          In: Haschek and Rousseaux\u2019s Handbook of Toxicologic Pathology, 3rd ed. WM Haschek, CG          Rousseaux, and MA Wallig (eds). Academic Press, San Diego. 2219\u20132275.          2013.","DOI":"10.1016\/B978-0-12-415759-0.00055-8"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10.  Monteiro-Riviere              NA. Comparative anatomy,          physiology, and biochemistry of mammalian skin. In: Dermal and Ocular Toxicology:          Fundamentals and Methods. DW Hobson (ed). CRC press, Boca Raton. 3\u201371.          1991.","DOI":"10.1201\/9781003069126-2"},{"key":"11","unstructured":"11.  Muller              GH,                Kirk              RW, and                Scott              DW. Structure and function of          the skin. In: Small Animal Dermatology, 4th ed. GH Muller, RW Kirk, and DW Scott (eds). WB          Saunders, Philadelphia. 1\u201348. 1989."},{"key":"12","doi-asserted-by":"crossref","unstructured":"12.  Yamate              J. Chapter 19 The skin and          subcutis. In: Boorman\u2019s Pathology of the Rat. Reference and Atlas, 2nd ed. AW Suttie (ed).          Academic Press, Oxford. 323\u2013345. 2018.","DOI":"10.1016\/B978-0-12-391448-4.00019-8"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13.  van                Smeden              J, and                Bouwstra              JA. Stratum            corneum lipids: their role for the skin barrier function in healthy subjects and atopic            dermatitis patients. Curr Probl Dermatol.            49: 8\u201326. 2016.","DOI":"10.1159\/000441540"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14.  Kartasova              T,                Darwiche              N,                Kohno              Y,                Koizumi              H,                Osada              S,                Huh              N,                Lichti              U,                Steinert              PM, and                Kuroki              T. Sequence and            expression patterns of mouse SPR1: correlation of expression with epithelial            function. J Invest Dermatol. 106:            294\u2013304. 1996.","DOI":"10.1111\/1523-1747.ep12340741"},{"key":"15","doi-asserted-by":"publisher","unstructured":"15.  Hohl              D,                Ruf Olano              B,                de Viragh              PA,                Huber              M,                Detrisac              CJ,                Schnyder              UW, and                Roop              DR. Expression            patterns of loricrin in various species and tissues.            Differentiation. 54:            25\u201334. 1993.","DOI":"10.1111\/j.1432-0436.1993.tb00656.x"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16.  Hohl              D,                de Viragh              PA,                Amiguet-Barras              F,                Gibbs              S,                Backendorf              C, and                Huber              M. The small            proline-rich proteins constitute a multigene family of differentially regulated            cornified cell envelope precursor proteins. J Invest            Dermatol. 104: 902\u2013909.            1995.","DOI":"10.1111\/1523-1747.ep12606176"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17.  Yoshida              K,                Kubo              A,                Fujita              H,                Yokouchi              M,                Ishii              K,                Kawasaki              H,                Nomura              T,                Shimizu              H,                Kouyama              K,                Ebihara              T,                Nagao              K, and                Amagai              M. Distinct            behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight            junctions in patients with atopic dermatitis. J Allergy Clin            Immunol. 134: 856\u2013864.            2014.","DOI":"10.1016\/j.jaci.2014.08.001"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18.  Loser              K, and                Beissert              S. Dendritic            cells and T cells in the regulation of cutaneous immunity. Adv            Dermatol. 23: 307\u2013333.            2007.","DOI":"10.1016\/j.yadr.2007.07.014"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19.  Kubo              A,                Nagao              K,                Yokouchi              M,                Sasaki              H, and                Amagai              M. External            antigen uptake by Langerhans cells with reorganization of epidermal tight junction            barriers. J Exp Med. 206:            2937\u20132946. 2009.","DOI":"10.1084\/jem.20091527"},{"key":"20","unstructured":"20.  Ginn              PE,                Mansell              JEKL, and                Rakich              PM. Chapter 5: Skin and          appendages. In: Pathology of Domestic Animals. Volume 1, 5th ed. MG Maxie (ed). Elsevier,          Philadelphia. 553\u2013781. 2007."},{"key":"21","doi-asserted-by":"crossref","unstructured":"21.  Yoshitomi              K,                Elwell              MR, and                Boorman              GA. Pathology            and incidence of amelanotic melanomas of the skin in F-344\/N rats.            Toxicol Pathol. 23:            16\u201325. 1995.","DOI":"10.1177\/019262339502300103"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22.  Greaves              P. Chapter 2. Integumentary          system. In: Histopathology of Preclinical Toxicity Studies, 4th ed. Academic Press, San          Diego. 11\u201368. 2012.","DOI":"10.1016\/B978-0-444-53856-7.00002-6"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23.  Sandby-M\u00f8ller              J,                Poulsen              T, and                Wulf              HC. Epidermal            thickness at different body sites: relationship to age, gender, pigmentation, blood            content, skin type and smoking habits. Acta Derm            Venereol. 83: 410\u2013413.            2003.","DOI":"10.1080\/00015550310015419"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24.  Calabro              K,                Curtis              A,                Galarneau              JR,                Krucker              T, and                Bigio              IJ. Gender            variations in the optical properties of skin in murine animal models.            J Biomed Opt. 16: 011008,            011008\u20138. 2011.","DOI":"10.1117\/1.3525565"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25.  Azzi              L,                El-Alfy              M,                Martel              C, and                Labrie              F. Gender            differences in mouse skin morphology and specific effects of sex steroids and            dehydroepiandrosterone. J Invest Dermatol.            124: 22\u201327. 2005.","DOI":"10.1111\/j.0022-202X.2004.23545.x"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26.  Willard-Mack              C,                Ramani              T, and                Auletta              C.            Dermatotoxicology: safety evaluation of topical products in minipigs:            study designs and practical considerations. Toxicol            Pathol. 44: 382\u2013390.            2016.","DOI":"10.1177\/0192623315622585"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27.  Wakayama              A,                Kudaka              W,                Matsumoto              H,                Aoyama              H,                Ooyama              T,                Taira              Y,                Arakaki              Y,                Shimoji              Y,                Nakasone              T,                Nishihira              K,                Kaneshima              I,                Tamaki              T,                Yoshimi              N, and                Aoki              Y. Lymphatic            vessel involvement is predictive for lymph node metastasis and an important prognostic            factor in endometrial cancer. Int J Clin Oncol.            23: 532\u2013538. 2018.","DOI":"10.1007\/s10147-017-1227-6"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28.  Lowenstine              LJ. A primer of            primate pathology: lesions and nonlesions. Toxicol            Pathol. 31(Suppl):            92\u2013102. 2003.","DOI":"10.1080\/01926230390177668"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29.  Justiniano              H,                Berlingeri-Ramos              AC, and                S\u00e1nchez              JL. Pattern            analysis of drug-induced skin diseases. Am J            Dermatopathol. 30: 352\u2013369.            2008.","DOI":"10.1097\/DAD.0b013e3181722ef4"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30.  DeWitt              CA,                Siroy              AE, and                Stone              SP. Acneiform            eruptions associated with epidermal growth factor receptor-targeted            chemotherapy. J Am Acad Dermatol. 56:            500\u2013505. 2007.","DOI":"10.1016\/j.jaad.2006.06.046"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31.  Lavker              RM,                Sun              TT,                Oshima              H,                Barrandon              Y,                Akiyama              M,                Ferraris              C,                Chevalier              G,                Favier              B,                Jahoda              CA,                Dhouailly              D,                Panteleyev              AA, and                Christiano              AM. Hair            follicle stem cells. J Investig Dermatol Symp Proc.            8: 28\u201338. 2003.","DOI":"10.1046\/j.1523-1747.2003.12169.x"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32.  Cotsarelis              G. Gene            expression profiling gets to the root of human hair follicle stem cells.            J Clin Invest. 116:            19\u201322. 2006.","DOI":"10.1172\/JCI27490"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33.  Yang              CC, and                Cotsarelis              G. Review of            hair follicle dermal cells. J Dermatol Sci.            57: 2\u201311. 2010.","DOI":"10.1016\/j.jdermsci.2009.11.005"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34.  Ikeda              M, and                Okada              S. Fine            structure of the sinus hair (pillus labialis maxillaris) and its microvascular            architecture in the cat. Okajimas Folia Anat Jpn.            67: 365\u2013379. 1990.","DOI":"10.2535\/ofaj1936.67.5_365"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35.  Bock              FG. Comparative            anatomy and function of skin as related to experimental chemical            carcinogenesis. Prog Exp Tumor Res.          26: 5\u201317. 1983.","DOI":"10.1159\/000407249"},{"key":"36","unstructured":"36.  Jonson              E. Cycles and patterns of hair          growth. In: The Physiology and Pathophysiology of the Skin, Vol. 4. The Hair Follicle. A          Harrett (ed). Academic Press, New York. 1237\u20131254. 1977."},{"key":"37","doi-asserted-by":"crossref","unstructured":"37.  M\u00fcntener              T,                Doherr              MG,                Guscetti              F,                Suter              MM, and                Welle              MM. The canine            hair cycle\u2014a guide for the assessment of morphological and immunohistochemical            criteria. Vet Dermatol. 22:            383\u2013395. 2011.","DOI":"10.1111\/j.1365-3164.2011.00963.x"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38.  Ishihara              T,                Yamashita              H,                Sakurai              T,                Morita              J,                Sakamoto              K,                Ishii              A, and                Sasaki              M.            Morphological analysis of patchy thickening and reddish discoloration of            active hair growth areas in the skin of New Zealand White rabbits.            J Toxicol Pathol. 30:            315\u2013322. 2017.","DOI":"10.1293\/tox.2017-0033"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39.  Thai              KE, and                Sinclair              RD. Short            anagen hair with persistent synchronized pattern of scalp hair growth.            J Am Acad Dermatol. 49:            949\u2013951. 2003.","DOI":"10.1016\/S0190-9622(03)00453-5"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40.  Tanaka              T, and                Narisawa              Y.            Three-dimensional comparative study of Merkel cell distribution in            various body sites of guinea pigs and rats. Arch Dermatol            Res. 292: 173\u2013179.            2000.","DOI":"10.1007\/s004030050474"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41.  Farka\u0161              R. Apocrine            secretion: new insights into an old phenomenon. Biochim Biophys            Acta. 1850: 1740\u20131750.            2015.","DOI":"10.1016\/j.bbagen.2015.05.003"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42.  Pappas              A. Epidermal            surface lipids. Dermatoendocrinol. 1:            72\u201376. 2009.","DOI":"10.4161\/derm.1.2.7811"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43.  Zhang              L,                Zhang              X,                Du              L,                Zhang              C, and                Li              H. Cholinergic-            rather than adrenergic-induced sweating play a role in developing and developed rat            eccrine sweat glands. Exp Anim. 70:            218\u2013224. 2021.","DOI":"10.1538\/expanim.20-0144"},{"key":"44","unstructured":"44.OECD. OECD guideline for testing of chemicals          no.442B: Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA or -FCM. 25. June.          2018."},{"key":"45","unstructured":"45.  Belsito              DV. Chapter 19 Toxic response          of the skin. In: Casarett &amp; Doull\u2019s Toxicology: The Basic Science of Poisons, 9th ed.          CD Klaassen (ed). McGraw-Hill Education, New York. 953\u2013976.          2019."},{"key":"46","doi-asserted-by":"crossref","unstructured":"46.  Dunnill              CJ,                Al-Tameemi              W,                Collett              A,                Haslam              IS, and                Georgopoulos              NT. A clinical            and biological guide for understanding chemotherapy-induced alopecia and its            prevention. Oncologist. 23:            84\u201396. 2018.","DOI":"10.1634\/theoncologist.2017-0263"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47.  Hu              X,                Dong              M,                Liang              X,                Liu              Z, and                Li              Q. Reactive            oxygen species-mediated inflammation and apoptosis in hand-foot syndrome induced by            PEGylated liposomal doxorubicin. Int J Nanomedicine.            16: 471\u2013480. 2021.","DOI":"10.2147\/IJN.S280187"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48.  Wikramanayake              TC,                Amini              S,                Simon              J,                Mauro              LM,                Elgart              G,                Schachner              LA, and                Jimenez              JJ. A novel rat            model for chemotherapy-induced alopecia. Clin Exp            Dermatol. 37: 284\u2013289.            2012.","DOI":"10.1111\/j.1365-2230.2011.04239.x"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49.  Poet              TS, and                McDougal              JN. Skin            absorption and human risk assessment. Chem Biol            Interact. 140: 19\u201334.            2002.","DOI":"10.1016\/S0009-2797(02)00013-3"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50.  Bormann              JL, and                Maibach              HI. Effects of            anatomical location on <i>in vivo<\/i> percutaneous penetration in            man. Cutan Ocul Toxicol. 39:            213\u2013222. 2020.","DOI":"10.1080\/15569527.2020.1787434"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51.  Tagami              H.            Location-related differences in structure and function of the stratum            corneum with special emphasis on those of the facial skin. Int J            Cosmet Sci. 30: 413\u2013434.            2008.","DOI":"10.1111\/j.1468-2494.2008.00459.x"},{"key":"52","unstructured":"52.  Slitt              AL. Chapter 5 Absorption,          distribution, and excretion of toxicants. In: Casarett &amp; Doull\u2019s Toxicology: The Basic          Science of Poisons, 9th ed. CD Klaassen (ed). McGraw-Hill Education, New York. 159\u2013192.            2019."}],"container-title":["Journal of Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/tox\/36\/2\/36_2022-0103\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T03:42:52Z","timestamp":1681530172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/tox\/36\/2\/36_2022-0103\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1293\/tox.2022-0103","relation":{},"ISSN":["0914-9198","1881-915X"],"issn-type":[{"value":"0914-9198","type":"print"},{"value":"1881-915X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023]]},"article-number":"2022-0103"}}