{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:24Z","timestamp":1786977144991,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,12,4]],"date-time":"2014-12-04T00:00:00Z","timestamp":1417651200000},"content-version":"vor","delay-in-days":3,"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":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      S\u201053482, 7\u2010fluoro\u20106\u2010[(3,4,5,6\u2010tetrahydro)phthalimido]\u20104\u2010(2\u2010propynyl)\u20101,4\u2010benzoxazin\u20103(2H)\u2010one (flumioxazin), is an\n                      <jats:italic>N<\/jats:italic>\n                      \u2010phenylimide herbicide and developmentally toxic to rats, but not to rabbits. The day of greatest sensitivity to S\u201053482 is gestational day (GD) 12 in rats. There is a compound\u2010specific difference in developmental toxicity among structurally similar compounds including S\u201023121 (\n                      <jats:italic>N<\/jats:italic>\n                      \u2010[4\u2010chloro\u20102\u2010fluoro\u20105\u2010[(1\u2010methyl\u20102\u2010propynyl)oxy]phenyl]\u20103,4,5,6\u2010tetrahydrophthalimide; teratogenic) and S\u201023031 (pentyl 2\u2010chloro\u20104\u2010fluoro\u20105\u2010(3,4,5,6\u2010tetrahydrophthalimido)phenoxyacetate (flumiclorac pentyl); nonteratogenic). The herbicidal action is due to photodynamic action of accumulating protoporphyrin IX (PPIX), resulting from the inhibition of protoporphyrinogen oxidase (PPO), an enzyme in porphyrin biosynthesis. Species difference in PPIX accumulation in embryos corresponded to those of the developmental toxicity. Our objective in this study was to further investigate a link between PPIX accumulation resulting from PPO inhibition and developmental toxicity. This article is part of a series of studies to be published serially.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>To investigate compound\u2010specific differences, each compound was orally administered to rats on GD 12. To define peak period of PPIX accumulation, single oral treatments of S\u201053482 were given to rats or rabbits at 19:30 on GD 10 through GD 15. PPIX was extracted from embryos 14 hr after treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Remarkable PPIX accumulation was observed when treated with S\u201053482 or S\u201023121, but not with S\u201023031. The greatest accumulation of PPIX was observed when treated with S\u201053482 at 19:30 on GD 11 or GD 12. No PPIX accumulation was found on any GDs in rabbits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The developmentally toxic compounds caused PPIX accumulation in embryos. The peak period of PPIX accumulation corresponded to that of developmental effects. This correlation suggests a close link between PPO inhibition and developmental abnormality<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdrb.21133","type":"journal-article","created":{"date-parts":[[2014,12,7]],"date-time":"2014-12-07T12:06:46Z","timestamp":1417954006000},"page":"429-437","source":"Crossref","is-referenced-by-count":10,"title":["Close Link between Protoporphyrin IX Accumulation and Developmental Toxicity Induced by\n                    <i>N<\/i>\n                    \u2010Phenylimide Herbicides in Rats"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-8255","authenticated-orcid":false,"given":"Satoshi","family":"Kawamura","sequence":"first","affiliation":[{"name":"Environmental Health Science Laboratory Sumitomo Chemical Co., Ltd  Konohana\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terushige","family":"Kato","sequence":"additional","affiliation":[{"name":"Environmental 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