Document KzRpj6ybKDmRD3VNz63KXdrjw

inia ntruni is mt r^urtnn i OF Biochemical Research Laboratory THE DOW CHEMIPAL COMPANY **HE DOW CHEMICAL COMPANY VAPOR TOHCITY OF ETHYLENE BICHLORIDE (DICHLOROETHANE, C*H4C1*) LITERATURE SURVEY FU.'TB.g-EGA ch*. 1219 Rac'd 1-19-40 Fin'd. 1-23-40 Work Br H. 0. Sp I1C T To Legal Department- chock A. Groaning, Jr. C. A. Campbell Dr. W. R. Veazey Ropt.Br Single Exposures No doubt the work by Sayers et al (Public Health Reports 45, 225-239 (1930)) is by far the most extensive investigation that has been made. These workers determined the acute physiological response of guinea pigs exposed to air containing ethylene dichloride vapors. The concentrations of vapor and periods of exposure ranged from those whioh produced death in a few minutes to those that caused no apparent effeot after several hours. In the order of occurrence the symptoms produced in these guinea pigs were eye and nose irritation, vertijjo, static and motor ataxia, retching movements, semi consciousness and unconsciousness accompanied by uncoordinated movements of the extremities, and death. The results may be tabulated as follows: 347 36 16C 439 oo 136885 CONFIDENTIAL mg/1 400-300 240 ppm 100,000200,000 60,000 40 10,000 24 6,000 14 3,500 4 1,000 Biochemical Research Laboratory T3.3-E6A Page 2 Duration Pew minutes 30 minutes 25 minutes 30-60 minutes 60 minutes Several hours Effect Death After 10 minutes eye and nose irritation, giddiness, ataxia, convulsions, loss of conscious ness. Death in 30 minut s. Same symptoms. Many delayed deaths. Dangerous No severe disturbance Very slight symptoms. Maximum amount without serious disturbances after several (3) hours. DO 136886 confidentIal DO 1 3 6 8 8 7 CONFTDFNTTi Animal Mice Mice Mice Mi ce Mi ce Mice Mice Mice Mice Guinea PiSs mg/1 11.5 23 23 57 114 35 100 15-20 20 40 ppm (2,750) (5,500) (5,500) (13,700) (27,400) 8,700 24,000 3,7005,000 5,000 10,000 Time exposed 123 minutes 54 minutes 70 minutes 36 minutes 15 minutes 2 hours 30 minutes ? ? ? Biochemical Research Laboratory T3.3-26A Page 3 Result Reference Death after 1 day Death after 1 day Death during ex posure. Death during ex posure. MUller, J Arch, exper. Path. u. Phaimakol., 109, 276 (1925) (Cited by von Get t ingen, J. Ind. Hyg. & Tox. 19: 349-448 (1937)) Moribund within 1 day Death of a majority Lazarew (1929) of the mice. Pantelitsch (1933) _Death of a majority {1 Cited bJy Browning, p. 162) of the mice. Light narcosis Lazarew (1929) {Cited by Browning, p. 162) Deep narcosis Deep narcosis It Biochemical Research Laboratory T3.3-26A Page 4 Repeated Exposures "No chronic symptoms arising from prolonged exposure to ethylene dichloride have been reported----- 'I (Browning, 1937, p. 165) Apparently no repeated exposures of laboratory animals to ethylene dichloride have been made. Mode of Action Muller (Arch. Exp. Path. Pharmak., 109. 276 (1925)) reported that ethylene dichloride produced severe effects upon the liver, however, these results are unconfirmed by more recent workers (Browning, p. 162). In the acutely exposed cavies of Sayers et al the chief pathological lesions ` , . were found in the lung with secondary changes m the kidney. Many investigators (See Browning, p. 163) have reported corneal opacity following inhalation of ethylene dichloride vapor. This opacity generally disappeared after several months. Field Studies No extensive field studies have been made in the case of ethylene dichloride. There has been one case reported following the drinking of two ounces of the material (Hueper md Smith, Fatal ethylene dichloride poisoning, Am. J. Med. Sci., 189, 778 (1935)). A case of acute, but not very severe, symptoms after exposure to the vapor of ethylene dichloride was reported in 00 1.36S88 CONFIDENTIAL Biochemical Research Laboratory T3.3-26A Page 5 England in 1932. The subject who was employed in a dye works complained of vomiting, diarrhea, giddiness and drowsiness, with slight breathlessness after recovery from the attack. (Cited by Browning, 1937, p. 165) Smyth (Report of the Committee on Volatile Solvents to the Industrial Hygiene Section of the American Public Health Association, 1939, p. 6) in a survey of the literature for 1937 and 1938 listed five reported cases of ethylene dichloride poisoning but found no fatalities due to this material. Toxicological Significance of Ethylene Dichloride A direct quotation from Sayers et al (Sayers, Yant, './site and Patty, .Acute Response of Guinea Pigs to Vapors of Some Hew Commercial Compounds. I. Hthylene Bichloride. Reprint yl349. Public Health Reports 45, 225-259 (1950))is of particular significance. "A comparison of the results obtained for ethylene dichloride v:ith those reported in tne literature for other compounds indicates that for single exposures and periods of an hour or more the toxicity of ethylene dichloride is of about tlie same order as that of gasoline, bensene, carbon tetrachloride, and chloroform. For periods of less than an hour it is less toxic than these compounds. no 1 3fc>8B9 confwenttai Biochemical Research Laboratory TS3-* 26A Page 6 "The odor of ethylene dichloride is distinct and noticeable in relatively safe concentrations. Also, it produces marked symptoms of dizziness in concentrations that will not cause permanent damage. If the odor or the first symptoms of dizziness are token as a warning of the presence of vapor and the person retires from the contaminated atmosphere it is not likely that injury vdll occur from acute exposure. Serious effects might easily result, however, from forced exposure, involuntary exposure, or exposure to a high concentration of vapor v/} i ch would cause unconsciousness before escape could be made. "In conclusion, it should be stated that the investigation described in this report v;as designed to give information pertaining to the relative toxicity and effects of a single exposure to ethylene dichloride vapor. Accordingly the results can not be interpreted as applying to the possible effects of repeated exposure. There were, however, no indications that repeated exposure might cause a chronic type of poisoning of a nature other than the logical er-'edwtion of a possible accumulation of the effects notwd and described for acute poisoning, when the daily exposure is sufficient to cause the latter. It is always a safe recommendation, liovever, that the manufacture, distribution, and use of new chemicals of this nature accompanied by a period of observation of the effect on health, so that if poisoning occurs it may be detected in the incipient stage, therby obviating serious results and permitting the design of a remftay for the situation. oo ^ 3689 Biochemical Research Laboratory T3.3-26A Page 7 Allowable Limits On hundred ppm. has been suggested for Massachusetts as the maximum allowable concentration of ethylene dichloride. (Comnonvrealth of Massachusetts Department of Labor and Industries, Division of Occupational Hygiene, May 1938) The U. S. Public Health Service, Connecticut Health Department, California Ind. Acc. Comm., and Wisconsin Ind. Comm, had not established definite limits for ethylene dichloride by May, 1938. Note Concerning the Answer Given in the Queries and Minor Notes Section of the J. A, X A. (1952) on the Toxicity of .ethylene Dichloride Browning (Toxicity of Industrial and Organic Solvents, His Majesty* s Stationery Office, London, (1937) p. 164) takes special note of the answer given in the I. A. H. A. (1932, p. 1401) in regard to the toxicity of ethylene dichloride. Quoting from Browning, p. 164: "An answer to a guery in the Journal of the .unerican Medical Association in 1932 would give the impression that dichloroethane is one of the most toxic solvents used in industry, but, except for the account of a fatal case from drinking the fluid (Heuper and Smith, 1935) and a case of not great severity reported to the Home Office in 1932, there is little information as to the symptoms and none to any organic lesions produced by its use. oo 1 -[DFNtT AL. 0.0NF Biochemical Research Laboratory T3.3-26A Page 8 The author of the 'Answer' above referred to evidently bases his statement on an analogy with carbon tetrachloride and on the evidence of animal experiments. He states: 'In addition to nausea, workmen with any considerable exposure, may develop headache, dizziness, diarrhea, hemorrhage into the intestinal tract, hemorrhage into the lungs or pleural cavity and irritation of the respiratory tract. Higher concentrations may lead to necrosis of the liver. It is believed that persons addicted to alcohol are especially susceptible to the action of the substance. At least this is true for carbon tetrachloride.' He gives no authority for these statements." It should be noted that this ''answer" is based entirely upon inference and that it is definitely misleading in the light of practical industrial experience with ethylene dichloride. One should notice particularly that the author of the "answer" gives no authority for his statements and was probably stating his personal opinion which, in all probability was based upon an exceedingly conservative analogy with the better known halogenated hydrocarbons. Significant Articles and Reviews on the Toxicology of Ethylene Dichloride (1) Sayers, R. R., Yant, W. R., Waite, C. ?., and Patty, F. A., Acute Response of Guinea Pigs to Vapors of Some New Commercial Organic Compounds. I. Ethylene Dichloride. Public Health Reports 45, 225-239 (1930). Reprint No. 1349. CnOONF1 W36eN8T^IW. Biochemical Research Laboratory T3.3-T.6A Page 9 (2) Browning, E.t Toxicity of Industrial Organic Solvents, His Majesty1 s Stationery Office, London (1937) p. 161-166. (3) Smyth, H. F., Jr., Report of the Committee on Volatile Solvents to the Industrial Hygiene Section of the American Public Health Association, (1939) p. 6. (4) von Oettingen, V/. F., The Halogenated Hydrocarbons: Their Toxicity and Potential Dangers., I. Ind. Hyg. & Tox. 19, 394-397 (1957). ACA DO 1.36893 confidential. S. B. Heath S. U. Adame December 10, 1937 Toxiolty of dicbloroethane, sym. TO - 7 rj. 3 -Z'to TJ. 4-AC,-/ ft-1^5^ Aooordlng to our Information on animal experiments dlchloroethane has a vapor toxicity of about the same order as that of carbon tetrachloride. Slight symptoms after several hours exposure. Maximum amount that may be inhaled for 1 hr. without serious disturbance Dangerous for 30-60 minutes. Rapidly fatal c,h4ci. 0.1* CC1. o.iejt 0.35* 0.6-0.6% 10-0# 0.4-0.6$ 2.4-3.& 4.8-6.356 BIOCHxaIICaL RuSi^RCH LABORATORY JR 36894 .DoONF^T.DF.Ntl6l