Document rp815ZvLVZQxYgG1mr4x5wm7J

135 -I: Diagnosis and jon injury. J Occup ki uaa accidents: OuUM o( patients. Read U. 1 Planning and Ctt, land. Wash, 1909. hazards from radiatin and defense, in Swan.VJ: Occupational Du^ Lee & Pebiger Public : of radiation induced . idiation at Place n/ It . -tional Sympotium. I.,, me (Imprimerie H) > stogical aspects of xeedingt of the Symp, Radiation Accidenti. W mergy, 1969, pp 189-H-' .agal aspects of mdii-u the Seminar on Moi. tadiation Accidents, K, must be a better wit .for radiation injury. i WD (eds): Diagruuii tIf^nuciidee. Amaterdi: icV \ PP 617-620. renaL a of radiation ic. -noaia and compensation r a result of work involve, ition. Joint Report o( " t . the Workmen's Ownie 7 Med 2:503-507,196a :edical and scientific Ur to radiation exposure. WD (eds): Diagnoti$ ladionuclidct. Amstenin ion, 1968, pp 621-628. Tumors of the Respiratory Tract Induced by Inhalation of Bis(Chloromethyl)Ether '~Lney Laskin; Marvin Kuschner, MD; zJvrt T. Drew, PhD; Vincent P. Cappiello, MS; +d S'orton Nelson, PhD, New York Squamous ceH carcinomas of the lung and rfwsloneuroepithoUomaa of the olfactory epitwOvm were produced In high Incidence In rale otowlng Inhalation of 0.1 ppm of bis(chloro> ethyl) ether. These findings imply a significant reentlal occupational hazard. -ubmitled for publication Feb 6, 1971; accepted 'ml L t ram the Institute and Department of Environwntal Medicine and the Department of Pathology, 5vw York University Medical Center, New York, v Kunrhner is not at State University of New i it it Stony Brook, Health Sciences Center, De triment of Pathology, Stony Brook. Dr. Drew is ** et the National Institute of Environmental With Sciences, Research Triangle Park, North vwlinn. Krprint requests to New York University Medical mir. Department of Environmental Medicine, 560 ' nt Ave. New York 10016 (Professor Laskin). IN 1968, VanDuuren et al1 presented some preliminary observations on the bio logical effects of two halogenated ethers, chloromethyl methyl ether and bis(chloromethyl)ether. A definitive examina tion of the carcinogenicity of these com pounds, as well as other halogen ethers as initiators or promoters, or both, was subse quently published by VanDuuren et al.1 In these studies, skin painting in mice and subcutaneous injection in rats were the as say systems employed. Particularly striking. in VonDuuten's study was the carcinogenici ty of bis(chloromethyl)ether as judged by the production of skin papillomas and carci nomas in mouse skin and subcutaneous fibrosarcomas in rats. Fig 1.--Keratinizing squamous call carcinoma of the lung In a rat axposad to bh(chloeomethyl)ather by inhalation. The tumor Is wail differentiated in aome areas and moderately anaplastic in others (hematoxylin-eosln, reduced from X200). Arch Environ Health--Vol 23, Aug 1971 02305 EPI* 136 BlS(CHLOROMETHYl)ETHER TUMORS--LASKIN ET AL TranspJ Cholang Examining the effects of a single subcuta neous injection in newborn mice, Gargus et al3 found a higher incidence in animals with pulmonary adenomas and more tumors per mouse in those receiving bis (chloromethyl)ether than in those receiving chloromethyl methyl ether or in uninjected controls. In light of these findings and in view of the fact that industrial exposure to these volatile liquids was more likely to be via the respiratory tract than the skin, we under took to examine their effects by means of animal inhalation exposures. A series of graded exposures of rats to both chloromethyl methyl ether and bis(chloromethyl)ether was begun and animals have been under observation for some time. A startling tumor yield at extremely low concentrations of bis(chloromethyl)ether leads us to submit this preliminary report particularly in view of the potential hazard to individuals occupationally exposed to these widely used alkylating agents. They are extensively employed in the lab oratory as intermediates in organic syntheses and, hi indistty, are used in the treatment of textiles, in the fabrication of polymers, as solvents for polymerization reactions, and in the preparation of ion exchange resins. This report relates only to the findings to date in a group of 30 Sprague-Dawley rats exposed to bis (chloromethyl)ether for a to tal of 101 exposures. The animals were ex posed to 0.1 ppm for six hours per day five days per week. All 30 animals were dead I tefo G. Glaser, fig 3.--Microscopic appearance of erthesionwro epithelioma Induced by Inhalation of btafchloromethyi)- t Unit Gablike, l athsr. Characteristic "rosette*" are saan (hatnatujfe eosin, raducad from x210). 6S9 days after the start of the exposure, j Gross and histological examinations of 19 of these 30 animals have been completed. Five of the 19 had squamous cell carcinomas of | the lung (Fig 1) and five had esthesioneuroepitheliomas arising from the olfactory ep ithelium (Fig 2 and 3), invading the sinus es, the cranial vault, and the brain. One animal had both tumors so that the total number of tumor-bearing animals was nine of the 19 examined. The pulmonary carcino mas were seen in animals who died from 332 to 463 days after the onset of exposure. The nasal tumors were seen in animals dyirf from 346 to 488 days after onset of expo sure. Multiple tumors of the same type in the lung and in nasal cavity have been seen in animals exposed for shorter periods. These will be reported when the study is complete. This investigation was supported by contract PHPG6-962 from the Public Health Service, Nation*1 Cancer Institute, US Department of Health. Ed cation and Welfare, Washington, DC. end is part d a center program au|iported by the National Imp- .tute of Environmental Health Sciences, grant U 00260 j [i References 1 We report a i tenor, derived fr t-ecetylaminofluor east In Ihe done varoplanted Into tee months later, N tite of bansp ton, multinodular scteriitlc of tdrrl vmtplgnta of tun t*6 culture all dr nor. Thoao with petit of Uver iron (action* did no transplant* tftrout H*ly malignant, t W*. T HE carcinogt fduorene have * number of invi `-ninofluorene is trit-ty of tumor -`pemed localiz ''oral potential r,*t studied. Wf tmnt transplar liver of a h -*>rcne, which d. 1. Va'nDuuten Hr, Goldschmidt JIM. Katz G * j al: Alpha haloethers: A new type of alkylating t*r ' cinogen. Arch Environ Health 16:472-478, 19* ; 2. VanDuuren Bf, Sivak A, Goldschmidt BM. * , al: Carcinogenicity of halo-ethers. J Not Cancer U* i 43:481-486, 1969. . 3. Gargus JL. Reese WH Jr, Butler HA: tion of lung adenomas in newborn mice by w (chloromethyl)ether. Toxic Appl Pharmacol 1-** 96, 1969. 'J*nit(ed for pub A 1971. J"*' `he Depart Massachust Vendee, Mas*. , retiue*ts u ^'cnees. Room '*"meT)e.chnology, EPL 02306 Arch Environ Health--Vol S3, Aug 1971