{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:36:23Z","timestamp":1788568583157,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2003,10,23]],"date-time":"2003-10-23T00:00:00Z","timestamp":1066867200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Detection of chemically induced effects on male fertility and on testicular spermatogenesis in particular, has become of increasing concern. More stringent regulatory guidelines, introduced by ICH, EPA and OECD (Table 1) have raised the awareness of toxicologists and pathologists for the need to conduct sensitive and careful evaluation of the male reproductive tract for potential toxic effects of administered compounds. With it has come confusion and in many cases, inappropriate procedures, often based on misunderstanding of what is required and on inadequate understanding of spermatogenesis. This article summarizes and discusses the main recommendations recently proposed by the Society of Toxicologic Pathology on recommended approaches for the evaluation of testicular and epididymal toxicity [Lanning LL, Creasy DM, Chapin RE, Mann PC, Barlow NJ, Regan KS, Goodman DG. Toxicologic Pathology 30:518\u2013531, 2002]. The major recommendations are:\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Use sexually mature animals to evaluate effects on spermatogenesis.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Sample left and right testes and epididymides and record organ weights.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Use modified Davidson's fixative to fix testes from all species from studies of 13 wks duration and less.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Examine transverse sections of the testes (including part of the rete), and longitudinal sections of the epididymides.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Embed tissues in paraffin wax.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>For rodent studies up to 28 days, examine periodic acid\u2010Schiff's\u2010hematoxylin stained sections. For all other studies examine hematoxylin and eosin stained sections.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Microscopic evaluation of the testis should be a\n                          <jats:italic>qualitative<\/jats:italic>\n                          evaluation carried out with an awareness of the spermatogenic cycle. Quantitative procedures are inappropriate for screening studies.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Nomenclature and grading of findings for spermatogenic disturbances will vary on a case by case basis<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                    <jats:italic>Birth Defects Res B<\/jats:italic>\n                    68:408\u2013415, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/bdrb.10041","type":"journal-article","created":{"date-parts":[[2003,10,24]],"date-time":"2003-10-24T04:10:14Z","timestamp":1066968614000},"page":"408-415","source":"Crossref","is-referenced-by-count":83,"title":["Evaluation of testicular toxicology: A synopsis and discussion of the recommendations proposed by the Society of Toxicologic Pathology"],"prefix":"10.1002","volume":"68","author":[{"given":"Dianne M.","family":"Creasy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,10,23]]},"reference":[{"key":"e_1_2_3_2_1","first-page":"28","volume-title":"An evaluation and interpretation of reproductive endpoints for human health risk assessment","author":"Chapin RE","year":"1999"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339702500201"},{"key":"e_1_2_3_4_1","first-page":"518","article-title":"Histological fixation of the testes: use of Davidson's fluid as an alternative to Bouin's fluid","volume":"36","author":"Creasy DM","year":"1999","journal-title":"Vet Pathol"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/019262301301418865"},{"key":"e_1_2_3_6_1","volume-title":"Current protocols in toxicology","author":"Creasy DM","year":"2002"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(86)90176-4"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod43.3.525"},{"key":"e_1_2_3_9_1","series-title":"Methods in toxicology. Vol. 3. Part A. Male reproductive toxicology","first-page":"86","author":"Hess RA","year":"1993"},{"key":"e_1_2_3_10_1","unstructured":"International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use.1995.Harmonized tripartite guidelines. ICH S5A: Reproductive toxicology: detection of toxicity to reproduction for medicinal product\/CPM\/IC\/13\/95 (adopted September 1993) and ICH S5B: Reproductive toxicology: toxicity to male fertility (addendum)\/CPM\/IC\/13\/95 (adopted 1995)."},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(79)90073-8"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.53.241"},{"key":"e_1_2_3_13_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1080\/01926230290105695","article-title":"Recommended approaches for the evaluation of testicular and epididymal toxicity","volume":"30","author":"Lanning LL","year":"2002","journal-title":"Toxicol Pathol"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230290105721"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(88)90159-5"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1992.tb00345.x"},{"key":"e_1_2_3_17_1","unstructured":"Organization for Economic Co\u2010Operation and Development.1995.Reproductio\/developmental toxicity screening test. In: Guideline for testing of chemicals. No. 421. Adopted July 27th 1995. Paris: OECD. p1\u201310."},{"key":"e_1_2_3_18_1","unstructured":"Organization for Economic Co\u2010operation and Development.2001.Proposal for updating Guideline 416: two generation reproduction toxicity study. In: Guideline for testing of chemicals. No. 416. Adopted January 22nd 2001. Paris: OECD. p1\u201313."},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040-8166(81)90011-2"},{"key":"e_1_2_3_20_1","volume-title":"Histological and histopathological evaluation of the testis","author":"Russell LD","year":"1990"},{"key":"e_1_2_3_21_1","unstructured":"U.S. Environmental Protection Agency.1998. Health effects test guidelines. OPPTS 870.3800. Reproduction and fertility effects. Available athttp\/\/www.epa.go\/OPPTS_harmonize\/870_health_effects_test_guideline\/serie\/870_3800.pdf."},{"key":"e_1_2_3_22_1","unstructured":"U.S. Environmental Protection Agency.1998. Health effects test guidelines. OPPTS 870.3150. 90\u2010Day oral toxicity in nonrodents. Available athttp\/\/www.epa.go\/OPPTS_harmonize\/870_health_effects_test_guideline\/serie\/870_3150.pdf."},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01541898"}],"container-title":["Birth Defects Research Part B: Developmental and Reproductive Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrb.10041","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrb.10041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T14:40:05Z","timestamp":1700232005000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrb.10041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["10.1002\/bdrb.10041"],"URL":"https:\/\/doi.org\/10.1002\/bdrb.10041","archive":["Portico"],"relation":{},"ISSN":["1542-9733","1542-9741"],"issn-type":[{"value":"1542-9733","type":"print"},{"value":"1542-9741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}