{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:51:07Z","timestamp":1790776267722,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T00:00:00Z","timestamp":1346025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Congenital Anomalies"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recently social concerns have been increasing about the effects of environmental factors on children's health, especially on their nervous systems. The U.S. Environmental Protection Agency (EPA) and the Organisation for Economic Co\u2010operation and Development (OECD) have published testing guidelines for developmental neurotoxicity (DNT). Approximately 110 guideline studies have been conducted to date. Importantly, information from these studies has provided data critical for regulatory decisions for a number of chemicals. However, the DNT guidelines do not always satisfy all stakeholders because of some uncertainties in their methodology, evaluation, and regulation. Methodological issues include incomplete harmonization between EPA and OECD guidelines, criticisms of the methodology for learning and memory testing, and unspecified positive control substances. Potential artifacts in morphometric neuropathological measures, criteria for observation measures, uncertainty of postnatal offspring exposure, especially in feeding studies, and extrapolation of data from rats to humans are major evaluation issues. In addition, there is some uncertainty in the use of an additional safety factor for susceptibility of infants and children. Moreover, the DNT guidelines have extensive time and cost requirements, use large numbers of animals, and there is a limited set of laboratories that can conduct the study. This paper reviews some of these issues and summarizes discussions from the symposium \u2018Developmental neurotoxicity testing: Scientific approaches towards the next generation to protecting the developing nervous system of children\u2019 held at the 2011 annual meeting of the Japanese Teratology Society.<\/jats:p>","DOI":"10.1111\/j.1741-4520.2012.00374.x","type":"journal-article","created":{"date-parts":[[2012,4,23]],"date-time":"2012-04-23T07:13:51Z","timestamp":1335165231000},"page":"122-128","source":"Crossref","is-referenced-by-count":96,"title":["Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation*"],"prefix":"10.1111","volume":"52","author":[{"given":"Ryozo","family":"Tsuji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Crofton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600713269"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310386247"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.6.1133"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2007.01.014"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9427"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2009.04.014"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2007.06.002"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2004.02.007"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.2011.1.009"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1542\/peds.53.1.2","article-title":"The later growth of the brain and its vulnerability","volume":"53","author":"Dobbing J","year":"1974","journal-title":"Pediatrics"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3782(79)90022-7"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1741-4520.2007.00148.x"},{"key":"e_1_2_5_14_1","unstructured":"GAO.2005.Chemical regulation: options exist to improve EPA's ability to assess health risks and manage its chemical review program. GAO\u201005\u2010458. U.S. Government Accounting Office. Washington D.C.http:\/\/www.gao.gov\/products\/GAO\u201005\u2010458[Accessed January 31 2012]."},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69665-7"},{"key":"e_1_2_5_16_1","unstructured":"HaradaT.2009.Research report of gathering information about methods for evaluations of developmental neurotoxicity induced by chemicals.http:\/\/www.fsc.go.jp\/fsciis\/survey\/show\/cho20090140001[<Japanese> Accessed January 31 2012]."},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110s3337"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0800168"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000392156.73751.7c"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.6115"},{"key":"e_1_2_5_21_1","first-page":"877","article-title":"Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities","volume":"156","author":"Landrigan PJ","year":"2002","journal-title":"Environ Health Perspect"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9841"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.11447"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.108-a262"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/es902057k"},{"key":"e_1_2_5_26_1","unstructured":"MEXT Japan.1999.Present state of escalation of violence bullying and refusal to attend school. Japanese Government Policies in Education Science and Culture 1999.http:\/\/www.mext.go.jp\/b_menu\/hakusho\/html\/hpad199901\/hpad199901_2_052.html[Accessed January 31 2012]."},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.01109s177"},{"key":"e_1_2_5_28_1","first-page":"197","article-title":"Collaborative studies on behavioral teratology by 46 laboratories: effects of behavioral teratogenicity chemicals on the learning behavior of the rat","volume":"25","author":"Mizutani M","year":"1985","journal-title":"Congenit Anom"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1741-4520.2001.tb00828.x"},{"key":"e_1_2_5_30_1","volume-title":"Toxicity testing: strategies to determine needs and priorities","author":"NRC","year":"1984"},{"key":"e_1_2_5_31_1","volume-title":"Appendix A: values and limitations of animal toxicity data, intentional human dosing studies for EPA regulatory purposes \u2013 scientific and ethical issues","author":"NRC","year":"2004"},{"key":"e_1_2_5_32_1","volume-title":"Toxicity testing in the 21st century: a vision and a strategy","author":"NRC","year":"2007"},{"key":"e_1_2_5_33_1","unstructured":"OECD.2007.OECD guidelines for the testing of chemicals\/section 4: health effects. 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