Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Nyska, A.
Right arrow Articles by Ghanayem, B. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nyska, A.
Right arrow Articles by Ghanayem, B. I.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ETHYLENE GLYCOL MONO-N-BUTYL ETHER
Medline Plus Health Information
*Osteonecrosis
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Disseminated Thrombosis and Bone Infarction in Female Rats Following Inhalation Exposure to 2-Butoxyethanol

Abraham Nyska

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, nyska@ niehs.nih.gov.

Robert R. Maronpot

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Philip H. Long

Procter & Gamble Pharmaceuticals, Cincinnati, Ohio 45242

Joseph H. Roycroft

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

James R. Hailey

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Gregory S. Travlos

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Burhan I. Ghanayem

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Groups of 10 male and 10 female F344/N rats were exposed to 0, 31, 62.5, 125, 250, and 500 ppm of 2-butoxyethanol (BE) by inhalation, 6 hr/day, 5 days/wk, for 13 wk. Four moribund female rats from the 500 ppm group were sacrificed during the first 4 days of exposure, and 1 moribund female from the same group was sacrificed during week 5. Dark irregular mottling and/or loss of the distal tail were noted in sacrificed moribund rats. Similar gross lesions were noted in the terminally sacrificed females exposed to 500 ppm BE. Histologic changes noted in the day 4 sacrificed moribund rats included disseminated thrombosis involving the coccygeal vertebrae, cardiac atrium, lungs, liver, pulp of the incisor teeth, and the submucosa of the anterior section of the nasal cavity. Alterations noted in coccygeal vertebrae from the 500 ppm sacrificed moribund rats included ischemic necrosis and/or degeneration of bone marrow cells, bone-lining cells, osteocytes (within cortical and trabecular bone), and chondrocytes (both articular and growth plate), changes that are consistent with an infarction process. The moribund female rat that was sacrificed during week 5 and those female rats treated with 500 ppm and sacrificed following 13 wk of treatment lacked thrombi, but they had coccygeal vertebral changes consistent with prior infarction and transient or complete bone growth arrest. No bone lesions or thrombi were noted in the male rats treated with the same doses of BE. In conclusion, exposure to 500 ppm BE vapors caused acute disseminated thrombosis and bone infarction in female rats. Possible pathogenic mechanisms are discussed.

Key Words: Rodent • ethylene glycol monobutyl ether • hemolysis • thrombosis • nasal cavity • bone

References

  • Boner H. and Erslew AJ (1994). The blood and lymphoid organs. In: Pathology, 2nd ed., E Rubin and JL Farber (eds). J. B. Lippincott Company, Philadelphia, pp. 994-1097.
  • Boor PJ, Gotlieb AI, Joseph EC, Kerns WD, Roth RA, and Tomaszewski KE (1995). Contemporary issues in toxicology. Chemical-induced vasculature injury. Toxicol. Appl. Pharmacol. 132: 177-195.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Chabra RS, Huff JE, Schwetz BS, and Selkirk J. (1990). An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program. Environ. Health Perspect. 86: 313-321.[Web of Science][Medline] [Order article via Infotrieve]
  • Chanas B., Ward S., Healy R., Nyska A., and Ghanayem BI (1999). Effect of Gender on the Hematotoxicity of 2-Butoxyethanol (BE) in F344 Rats. 38th Annual Meeting of The Society of Toxicology, March 14-18, 1999, in New Orleans, Louisiana (abstract).
  • Chien S., Usami S., and Bertles JF (1970). Abnormal rheology of oxygenated blood in sickle cell anemia. J. Clin. Invest. 49: 623-634.[Web of Science][Medline] [Order article via Infotrieve]
  • Cotran RS, Kumar V., and Robbins S. (1994). Diseases of red cells and bleeding disorders. In: Pathologic Basis of Disease, 5th ed., RS Cotran, V Kumar, and S Robbins (eds). W. B. Saunders Company, Philadelphia, pp. 583-628.
  • Dill AJ, Lee KM, Bates DJ, Anderson DJ, Johnson RE, Chou BJ, Burka LT, and Roycroft JH (1998). Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice. Toxicol. Appl. Pharmacol. 153: 211-226.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Garza JA (1990). Massive fat and necrotic bone marrow embolization in a previously undiagnosed patient with sickle cell disease. Am. J. Forensic Med. Pathol. 11: 83-88.[Web of Science][Medline] [Order article via Infotrieve]
  • Ghanayem B. (1996). An overview of the hematoxicity of ethylene glycol ethers. Occup. Med. 2: 253-268.
  • Ghanayem BI, Blair PC, Thompson HB, Maronpot RR, and Matthews HB (1987). Effect of age on the toxicity and metabolism of ethylene glycol monobutyl ether (2-butoxyethanol) in rats. Toxicol. Appl. Pharmacol. 91: 222-234.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ghanayem BI, Burka LT, and Matthews HB (1987). Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: Role of alcohol and aldehyde dehydrogenases. J. Pharmacol. Exp. Ther. 242: 222-231.[Abstract/Free Full Text]
  • Ghanayem BI, Sanchez IM, and Matthews HB (1992). Development of tolerance to 2-butoxyethanol-induced hemolytic anemia and studies to elucidate the underlying mechanisms. Toxicol. Appl. Pharmacol. 112: 198-206.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ghanayem BI and Sullivan CA (1993). Assessment of the hemolytic activity of 2-butoxyethanol and its major metabolite, butoxyacetic acid, in various mammals including humans. Hum. Exp. Toxicol. 12: 305-311.[Web of Science][Medline] [Order article via Infotrieve]
  • Gibson T. (March 23, 1984). A Market Analysis of 2-Butoxyethanol and 2-Butoxyethylacetate. Regulatory Impacts Branch, U.S. Environmental Protection Agency under subcontract EPA 36-5 of ICF Inc., contract 68-02-4055.
  • Grossblatt N (ed) (1996). Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, D.C.
  • Hayashi Y., Hasegawa H., Tanaka G., and Ohmae S. (1996). A 13-week oral repeated dose toxicity study of a new antineoplastic agent S-1 in rats. J. Toxicol. Sci. 21(suppl. 3): 505-526.[Medline] [Order article via Infotrieve]
  • Horton DP, Ferriero DM, and Mentzer WC (1995). Nontraumatic fat embolism syndrome in sickle cell anemia. Pediatr. Neurol. 12: 77-80.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Huo MH, Friedlander GE, and Marsh JS (1996). Orthopaedic manifestations of sickle-cell disease. Pediatr. Infect. Dis. J. 15: 725.[Web of Science][Medline] [Order article via Infotrieve]
  • Jay WL and Rowlands S. (1975). The stages of osmotic hemolysis. J. Physiol. 252: 817-832.[Abstract/Free Full Text]
  • Jones TC, Hunt RD, and King NW (1996). Disturbances of circulation. In: Veterinary Pathology, 6th ed., TC Jones, RD Hunt, and NW King (eds). Williams & Wilkins, Baltimore, pp. 159-176.
  • Kaysser TM, Wandersee NJ, Bronson RT, and Barker JE (1997). Thrombosis and secondary hemochromatosis play a major role in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis. Blood 90: 4610-4619.[Abstract/Free Full Text]
  • Mandell GA and Meek RS (1993). Infarctions of the ilia in young patients with sickle hemoglobinopathies. Clin. Nucl. Med. 18: 558-560.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mariscal I., Moffat C., Huebner B., and Seaman AC (1973). A mechanism of thrombosis requiring neither platelets nor thrombin. Scand. J. Haematol. 10: 390-400.[Web of Science][Medline] [Order article via Infotrieve]
  • National Toxicology Program ( 1993). Toxicity Studies of Ethylene Glycol Ethers—2-Methoxyethanol, 2-Ethoxyethanol, 2-Butoxyethanol Administered in Drinking Water to F344/N Rats and B6C3F1 Mice. Technical Report Series No. 26, NIH publication 93-3349, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Maryland.
  • National Toxicology Program ( 1998). Toxicology and Carcinogenesis Studies of 2-Butoxyethanol (CAS No. 11-76-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). NIH publication No. 98-3974, Public Health Service, U.S. Department of Health and Human Services, Bethesda, Maryland.
  • Nelson BK, Setzer JV, Brightwell WS, Mathinos PR, Kuczik MH, Weaver TE, and Goad PT (1984). Comparative inhalation teratogenicity of four glycol ether solvents and amino derivatives in rats. Environ. Health Perspect. 57: 261-271.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Onuba O. (1993). Bone disorders in sickle-cell disease. Int. Orthop. 17: 397-399.[Web of Science]
  • Palmer N. (1993). Bones and joints. In: Pathology of Domestic Animals, 4th ed., KVF Jubb, PC Kennedy, and N Palmer (eds). Academic Press, Inc., Baltimore, pp. 1-181.
  • Reed W. and Vichinsky EP (1998). New considerations in the treatment of sickle cell disease. Annu. Rev. Med. 49: 461-474.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Resar LM, Oliva MM, and Casella JF (1996). Skull infarction and epidural hematomas in a patient with sickle cell anemia. J. Pediatr. Hematol. Oncol. 18: 413-415.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Rodgers GP, Schechter AN, Noguchi CT, Klein HG, Nienhuis AW, and Bonner RF (1984). Periodic microcirculatory flow in patients with sickle-cell disease. N. Engl. J. Med. 311: 1534-1538.[Abstract]
  • Rosenberg AE (1994). Skeletal system and soft tissue tumors. In: Pathologic Basis of Disease, 5th ed., RS Cotran, V Kumar, and S Robbins (eds). W. B. Saunders Company, Philadelphia, pp. 1213-1271.
  • Schultze AE and Roth RA (1993). Fibrinolytic activity in blood and lungs of rats treated with monocrotaline pyrrole. Toxicol. Appl. Pharmacol. 121: 129-137.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Smith JA (1996). Bone disorders in sickle cell disease. Hematol. Oncol. Clin. North Am. 10: 1345-1356.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Sokoloff L. (1958). Idiopathic necrosis of bone in small laboratory animals. Arch. Pathol. 65: 323-326.[Web of Science]
  • Tucker MJ (1986). A survey of bone disease in the Alpk/AP Rat. J. Comp. Pathol. 96: 197-203.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Udden MM and Paton CS (1994). Hemolysis and deformability of erythrocytes exposed to butoxyacetic acid, a metabolite of 2-butoxyethanol. I. Sensitivity in rats and resistance in normal humans. J. Appl. Toxicol. 14: 91-96.[Web of Science][Medline] [Order article via Infotrieve]
  • Van Hoeven KH, Wanner JL, and Ballas SK (1997). Cytologic diagnosis of fat emboli in peripheral blood during sickle cell infarctive crisis. Diagn. Cytopathol. 17: 54-56.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ward S., Blair PC, and Ghanayem BI (1989). Hematologic effects of 2-butoxyethanol (BE) in vivo and its effect on the morphology of rat erythrocytes. Toxicologist 9: 1155.
  • Wintrobe MM, Lee GR, Boggs DR, Bithell TC, Foerster J., Athens JW, and Lukens JN (1981). Acquired coagulation disorders. In: Clinical Hematology, 8th ed., MM Wintrobe (ed). Lea & Febiger, Philadelphia, pp. 1206-1246.
  • Wintrobe MM, Lee GR, Boggs DR, Bithell TC, Foerster J. Athens JW, and Lukens JN (1981). Paroxysmal nocturnal hemoglobinuria (PNH). In: Clinical Hematology, 8th ed., MM Wintrobe (ed). Lea & Febiger, Philadelphia, pp. 978-990.
  • Woodard JC and Montgomery CA (1978). Musculoskeletal system. In: Pathology of Laboratory Animals, K Benirschke, FM Garner, and TC Jones (eds). Springer-Verlag Inc., New York, pp. 663-880.
  • Woodard JC and Webster Jss (1991). Skeletal system. In: Handbook of Toxicologic Pathology, WM Haschek and CG Rousseaux (eds). Academic Press Inc., San Diego, pp. 489-534.
  • Zbinden G. and Grimm L. (1985). Thrombosis effects of xenobiotics. Arch. Toxicol. 8(suppl.): 131-141.

Toxicologic Pathology, Vol. 27, No. 3, 287-294 (1999)
DOI: 10.1177/019262339902700304


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
Toxicol PatholHome page
D. N. Lewis, A. Nyska, K. Johnson, D. E. Malarkey, S. Ward, M. Streicker, S. Shabat, S. Peddada, and M. Nyska
2-Butoxyethanol Female-Rat Model of Hemolysis and Disseminated Thrombosis: X-Ray Characterization of Osteonecrosis and Growth-Plate Suppression
Toxicol Pathol, February 1, 2005; 33(2): 272 - 282.
[Abstract] [Full Text] [PDF]


Home page
International Journal of ToxicologyHome page
Annual Review of Cosmetic Ingredient Safety Assessments--2002/2003
International Journal of Toxicology, January 1, 2005; 24(1_suppl): 1 - 2.
[Full Text] [PDF]


Home page
Hum Exp ToxicolHome page
B I Ghanayem, S M Ward, B Chanas, and A Nyska
Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats
Human and Experimental Toxicology, March 1, 2000; 19(3): 185 - 192.
[Abstract] [PDF]


Home page
Toxicol PatholHome page
P. H. Long, R. R. Maronpot, B. I. Ghanayem, J. H. Roycroft, and A. Nyska
Dental Pulp Infarction in Female Rats Following Inhalation Exposure to 2-Butoxyethanol
Toxicol Pathol, March 1, 2000; 28(2): 246 - 252.
[Abstract] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Nyska, A.
Right arrow Articles by Ghanayem, B. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nyska, A.
Right arrow Articles by Ghanayem, B. I.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ETHYLENE GLYCOL MONO-N-BUTYL ETHER
Medline Plus Health Information
*Osteonecrosis
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?