Ocular thrombosis and retinal degeneration induced in female F344 rats by 2-butoxyethanol

Abstract

2-butoxyethanol, used extensively for domestic and industrial purposes, was tested in our experiments for its potential to cause damage to female rat ocular tissues. Female rats were previously found to be particularly sensitive to 2-butoxyethanol. A group of eight female F344 rats (2–3 months old) were exposed by gavage to 250 mg of 2-butoxyethanol/kg b.w. per day for 3 consecutive days and sacrificed 24 h after the last dose. Eight female rats received the dosing vehicle (water) and served as controls. At necropsy, petechial hemorrhages were noted on the sclera. Microscopic examination revealed treatmentrelated effects in the eyes, in addition to other known effects of BE exposure such as disseminated thrombosis and necrosis and infarction in various organs. The spectrum of histopathological changes noted in the eyes included hemorrhages localized in the posterior layers of the retina, leading to photoreceptor degeneration. Thrombi were identified in ciliary processes and limbal blood vessels. Histological changes suggestive of the retinal ischemic-infarctive process were also noted. Possible pathogenic mechanisms of 2-butoxyethanol-induced retinopathy are discussed.

Keywords

rat ethylene glycol monobutyl ether retina thrombosis

References

Gibson T. A market analysis of 2-butoxyethanol and 2-butoxyethylacetate. Prepared for the US Environmental Protection Agency, Regulatory Impact Branch, subcontract EPA 36-5 of ICF, Inc., contract no. 68-02-4055, 1984.

Ghanayem BI et al. Effect of age on the toxicity and metabolism of ethylene glycol monobutyl ether (2-butoxyethanol) in rats . Toxicology and Applied Pharmacology 1987; 91: 222–234 .

Ghanayem BI , Burka LT , Matthews HB . Metabolic basis of ethylene ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: Role of alcohol and aldehyde dehydrogenases . The Journal of Pharmacology and Experimental Therapeutics 1987; 242: 222–231 .

Ghanayem BI . Metabolic and cellular basis of 2-butoxyethanol-induced hemolytic anemia in rats and assessment of human risk in vitro . Biochemical Pharmacology 1989; 38: 1679–1684 .

National Toxicology Program. 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 Number 26, NIH publication 93-3349, US Department of Health and Human Services, Public Health Service, Bethesda, Maryland, 1993.

Ghanayem B . An overview of the hematoxicity of ethylene glycol ethers . Occupational Medicine 1996; 2: 253–268 .

Ward S , Blair PC , Ghanayem BI . Hematologic effects of 2-butoxyethanol (BE) in vivo and its effect on the morphology of rat erythrocytes . The Toxicologist 1989; 9: 1155–1155 .

National Toxicology Program. Toxicology and carcinogenesis studies of 2-Butoxyethanol (CAS No. 111-76-2) in F344/N rats and B6C3F1 mice (inhalation studies). Technical Report Series 484, Department of Health and Human Services, Public Health Service, Bethesda, Maryland. Report in preparation, 1998.

Aasmoe L , Winberg JO , Aarbakke J . The role of liver alcohol dehydrogenase isoenzymes in the oxidation of glycolethers in male and female rats . Toxicology and Applied Pharmacology 1998; 150: 86–90 .

10.

Dill AJ et al. Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice . Toxicology and Applied Pharmacology 1998; 153: 211–226 .

11.

Nyska A et al. Disseminated thrombosis and bone infarction in female rats following inhalation exposure to 2-Butoxyethanol. Toxicologic Pathology. In press. 1999.

12.

Udden MM , Paton CS . Hemolysis and deformability of erythrocytes exposed to butoxyacetic acid, a metabolite of 2-butoxyethanol: I. Sensitivity in rats and resistance in normal humans . Journal of Applied Toxicology 1994; 14: 91–96 .

13.

Grossblatt N (Ed.). Guide for the care and use of laboratory animals. National Academy Press, Washington, DC , 1996.

14.

Chhabra RS , Huff JE , Schwetz BS , Selkirk J . An overview of prechronic and chronic toxicity/ carcinogenicity experimental study designs and criteria used by the National Toxicology Program . Environmental Health Perspectives 1990; 86: 313–321 .

15.

Nyska A , Ghanayem BI , Long PH . BE-induced hemolytic anemia, thrombosis, and infarction in the female rat: A possible model for sickle cell anemia-associated thrombosis and infarction . The 18th International Symposium of the Society of Toxicologic Pathologists, Washington DC, June 1998.

16.

Ghanayem BI , Sanchez IM , Matthews HB . Development of tolerance to 2-butoxyethanol-induced hemolytic anemia and studies to elucidate the underlying mechanisms . Toxicology and Applied Pharmacology 1992; 112: 198–206 .

17.

Cotran RS , Kumar V , Robbins S . Diseases of red cells and bleeding disorders. In: Pathologic basis of disease, 5th edn. WB Saunders Co: Philadelphia , 1994: pp. 583–628.

18.

Lutty GA et al. Nonperfusion of retina and choroid in transgenic mouse models of sickle cell disease . Current Eye Research 1998; 17: 438–444 .

19.

Green WR . Retina. In: Ophthalmic Pathology. An atlas and text, 4th edn. W.B. Saunders Co: Philadelphia , 1996: pp. 667–1313.

20.

Boner H , Erslev AJ . The blood and lymphoid organs. In: Pathology. Rubin E , Farber JL (eds). 2nd edition. JB Lippincott: Philadelphia , 1994: pp. 995–1096.

21.

McLeod D , Goldberg M , Lutty G . Dual perspective analysis of vascular formations in sickle cell retinopathy . Archives of Ophthalmology 1993; 11: 1234–1245 .

22.

Saito Y et al. Experimental preretinal neovascularization by laser-induced venous thrombosis in rats . Current Eye Research 1997; 16: 26–33 .

23.

Silva-Araujo A , Tavares MA , Patacao MH , Carilino RM . Retinal hemorrhages associated with in utero exposure to cocaine. Experimental and clinical findings . Retina 1996; 16: 411–418 .