{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:58:50Z","timestamp":1777913930517,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T00:00:00Z","timestamp":1415664000000},"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":[[2015,6]]},"abstract":"<jats:p>The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg\/kg\/day was tolerated; 500 mg\/kg\/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and\/or dysplasia of the stomach and small intestine; 1,500 mg\/kg\/day resulted in deaths on day 5. In dogs, a single dose at \u2265250 mg\/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg\/kg\/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses \u226515 mg\/kg decreased systolic blood pressure (BP); 50 mg\/kg increased diastolic BP, heart rate, and change in blood pressure over time (+d P\/d t), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr.<\/jats:p>","DOI":"10.1177\/0192623314559103","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T21:29:13Z","timestamp":1415827753000},"page":"498-512","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Toxicity of Hydroxyurea in Rats and Dogs"],"prefix":"10.1177","volume":"43","author":[{"given":"Daniel","family":"Morton","sequence":"first","affiliation":[{"name":"Pfizer Inc., Andover, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori","family":"Reed","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Andover, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhu","family":"Huang","sequence":"additional","affiliation":[{"name":"Pfizer Inc., La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Marcek","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Austin-LaFrance","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie A.","family":"Northcott","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott H.","family":"Schelling","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Andover, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley E.","family":"Enerson","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Andover, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,11,11]]},"reference":[{"key":"bibr1-0192623314559103","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2007.00522.x"},{"key":"bibr2-0192623314559103","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709113371107"},{"key":"bibr3-0192623314559103","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505183322001"},{"key":"bibr4-0192623314559103","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.10.3986"},{"key":"bibr26-0192623314559103","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2005.04.012"},{"key":"bibr5-0192623314559103","unstructured":"Food and Drug Administration, Center for Drug Evaluation and Research. 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