Document qk4v3RB3wNDjyMz9opNOzb1aR

V- j , , *- J i*-> * . Carr, Goodson S. Lee, R C ( DISEASE PROFILE CHLORACNE ^ VUM V ^ C d ! . ^ OOi t. . tv., M I. DEFINITION CL A. Dictionary ..... ............... V* C' An acneiform eruption caused by exposure to certain chlorine containing compounds. ( ^ B. Symptoms t The condition is characterized by multiple closed comedones (blackheads) and pale yellow cysts that first appear on the skin below and to the outer sides of the eye and behind the ear (the so-called malar crescent). The lesions next spread to the ears, neck, and forehead. As the disease increases with severity, the lesions become more numerous and may involve every follicle in the affected areas. The chest, shoulders, back, ears, and genitalia are often involved. The hands, feet, legs, and nose are rarely affected by the lesions. Other manifestations of the disease include hyperpigmentation, hirsutism, conjunctivitis, itching, and skin reddening. i C. Duration Chloracne lesions usually accur three to four weeks after exposure to % the causative chemical agent and in severe cases have persisted as long as thirty years after exposure to the chemical has ceased. All but the most severe cases, however, usually clear within two to three years. Relapses of the disease may occur even in the absence of further contact with the causative chemical agent. D. Treatment Treatment is usually unsatisfactory. It entails the same sort of regimen used for treatment of acne vuigaris (teenage acne), i.e., o-.il antibiotics, acne surgery, dermabrasion, and oral doses of vitamin A and 3~cis-retinoic acid. C09617 Carr. Goooson & Lee. R C. Chloncne Page 2 E. Diagnostic Criteria The general practitioner may not distinguish chloracne from gene vulgaris. Moreover, a dermatologist who has had little experience with occupational dermatoses may also misdiagnose this condition. The microscopic appearance of chloracne lesions is unique. The sebaceous glands of the skin gradually disappear and are replaced with keratinous cysts. The age of the patient can also help in the diagnosis. Acne vulgaris generally occurs between the ages of thirteen and twenty-six, while chloracne * can appear at any age. Environmental and occupational exposure history is an especially important part of the differential diagnosis of chloracne. The particular chemical exposure responsible for causing chloracne, however, cannot be determined by examining a clinical case. Thus, if a patient has had exposure to more than one chloracnegen (chloracne-causing agent), it would be impossible for a clinician to determine which chloracnegen caused the condition. II. EVIDENCE RELATING DISEASE TO 2,4,5-T, TCDD, or 2,4-D EXPOSURE A. Human Studies 1. Industrial Accidents. The major studies of chloracne caused by exposure to TCDD formed in an uncontrolled reaction or industrial accident include: * 1949 -- Monsanto Plant, Nitro, West Virginia. 122 out of 250 exposed'individuals developed chloracne. (1978, K). 1953 -- BASF, Ludwigshafen, West Germany. 55 out of 75 exposed workers developed chloracne. (1973, O). 1964 -- Dow Plant, Midland, Michigan. 49 out of 61 exposed workers developed chloracne. (1980, F). 1968 -- Coalite Plant, Derbyshire, England. 79 out of 90 exposed workers developed chloracne. (1973, N). 009619 I Carr. Goodson & Lee. R C. Chloracne Page 3 i / SU3.ir:-T 1 1976 -- ICMESA Plant, Seveso, Italy. A reactor explosion spewed TCDD-containing material over a large, heavily populated area in Lombardy, Italy. Thirty thousand persons were screened for chloracne and 187 eases are diagnosed. (1978, L, M). 2- Occupational Exposures 1954 -- Boehringer Plant, Hamburg, Germany. 31 workers in the trichlorophenol division of a 2,4,5-T manufacturing plant developed chloracne. (1957.jp R). 1956 -- Diamond Alkali Factory, New Jersey. 29 workers developed chloracne. (1971, P). 1962 -- Goldstein diagnosed chloracne in a UJS. Department of Agriculture forest service worker who had sprayed the herbicide, Brush Blitz (containing 2,4,5-T) in the St. Francis National Forest near Ozark, Arkansas. (1962, Q). 1964 -- Spolana, Czechoslovakia. 80 workers in a 2,4,5-T factory developed chloracne. (1961, D). 1950 - 1971 -- Dow Plant, Midland, Michigan. 13 of 204 workers who were occupationally exposed to 2,4,5-T developed chloracne. These workers were chronically exposed to the manufacture of 2,4,5-T, but were not acutely exposed * to TCDD during the 1964 industrial accident at Dow. (1980, G). 3. Veteran Studies In 1982, the Veterans Administration formed a Task Force to study chloracne among veterans. The Task Force drew up a list of diagnostic criteria to be distributed to all 172 V.A. Hospitals and to be used in examining the veterans complaining of skin conditions. This criteria was reviewed by three eminent dermatologists, Raymond Suskind, M.D., of the University of Cincinnati, Donald Birmingham, M.D., retired from the University Hospital in Detroit, and James S. Taylor, M.D., of the Cleveland Clinic. The criteria are now in use at each of the 009619 Carr, Goodsn & Lee, R C. Chloracne Page 4 VU..* C ` --, >ta VJt. Medical Centers* In addition, each V.A. Center now staffed with a full- time consultant dermatologist to examine patients. The V.A. has diagnosed some eases of chloracne among veterans. 4. Other I In 1965, Dow contracted with Dr. Albert Kligman of the University of Pennsylvania to determine the dose of TCDD necessary to produce a chloracne response in humans. Dr. Kligman treated prisoner volunteers with two doses of jp TCDD ranging in amount from .2 ug to 8 ug. The doses were applied in an alcohol- chloroform solution to a one inch square area of skin: Chloracne was not produced in any of sixty volunteers. Dr. Kligman then, on his own initiative, increased the jadosage. Dr. Kligman gave each of ten volunteers total dosage of 7,500 ug of TCDD over a one month period. Eight of the ten men developed a chloracne condition which lasted from four to seven months. Thus, the threshold dose required to cause chloracne in humans is somewhere between 16 ug and 7,500 ug. It is doubtful that this range will ever be refined. TCDD became known as a suspect carcinogen in the early 1970Ts and therefore, it is no longer ethical to carry out such human experiments. (I960, E). B. Animal Studies 1. Primates Chloracne has been produced in the rhesus monkey by direct application ox TCDD. In addition to the characteristic lesions, the animals also have other reactions such as loss of hair on the face and disruption of meibomian glands located near the eye. (1979, 1). 2. Mammals The rabbit is the roost sensitive species to TCDD induction of chloracne. The sensitive inner surface of the rabbit ear has been used since 1941 as a standard test for chloracnegenecity. As little as .12 ug of TCDD will produce a G09620 Carr. Goodson & Lee, R C. Chloracne Page 5 C c* chloracnegenic reaction In the rabbit ear. Chloracne cannot, however, be produced on any other part of the rabbit's skin. (1982, B). Pure 2,4,S-T has been tested In the rabbit ear model and has not caused chloracne. (195?, R). 3. Rodents Chloracne can also be produced in the hairless mouse by application of TCDD. However, this species is much less sensitive than the rabbit to the P experimental induction of chloracne. (1982, B). 4. Other A chloracne response has not been produced in any other species. (1981, C). HI. ANALYSIS It has been conclusively proven that TCDD will cause chloracne in humans (1980, ). The sensitive rabbit ear test has also shown that pure 2,4,5-T is not capable of inducing chloracne (1957, R). No studies have shown that 2,4-D will produce chloracne in humans or animals. Chloracne;jens in the gaseous state (fumes) are the most potent inducers of chloracne. Solutions are less potent and solids are scarcely chloracnegenic at all. Chloracne is recognized as a symptom of systemic poisoning. It is possible, however, for an individual with a mild or moderate isase of chloracne to be otherwise perfectly healthy if the amount of chloracnegen in his system is insufficient to cause organ damage. The importance of the chloracne condition lies in the fact th at chloracne is the most sensitive indicator of TCDD exposure in humans. Thus, according to noted authorities, if an exposed individual has not received enough exposure to TCDD to develop chloracne, that individual will also not develop any other short or medium term effects from TCDD exposure. The long term effects of TCDD exposure a re still unknown, however, and i t cannot be assumed th at because CU9621 Carr. Goodson & Lee. P C. Chloracne Page 6 an individual was not diagnosed as having ehloracne that he eould not, in fact, develop a disease with a long latency period such as cancer. Also, Is mentioned before, this condition is easily misdiagnosed and mild cases can be overlooked. Thus, an individual who had undiagnosed ehloracne could have developed other short or medium term systemic health effects from the exposure. IV. PRINCIPAL DOCUMENTS A. 1983. Occupational Acne, Including Chloracne, Adams, Robert M. Copy Attached * B. 1982. Acnegenic Activity of 3-Methylcholanthrene and Benzo-a-pyrene, and a Comparative Study with 2,3,7,8-TCDD in the Rabbit and Hairless Mouse. Vos, J.G.; Van Leeuwen, FJC.R.; and DeJonge, P. Copy Attached C. 1981. Chloracne and Its Potential Clinical Implications. Crow, Kenneth 0. Copy Attached D. 1981. The Development and Prognosis of Chronic Intoxication by TCDD in Men. Pazderova-Veljlupkova, Jana; Nemcova, Marcela; Pickova, Jane; Jirasek, Luber; and Lukas, Edgar. Carr Document No. -- A-2520 Microfiche No.: -- A639 C7-D2 E. 1980. Direct Testimony of V.K. Rowe of Dow Chemical, EPA 2,4,5-T Hearings. November 13, 1980. Carr Document No. * A-1628 Microfiche No.: -- A496 D04-F02 p, F . 1980. The Mortality Experience of Employees Exposed to 2,3.7,8-TCDP. Cook, R.R.; Townsend, J.C.; and Silverstein, L.G. Carr Document No. -- A-976 Microfiche No.: -- A294 B7-B12 G. I960. The Mortality Analysis of Employees Engaged in the Manufacture of 2,4,5-T. O tt, M.G.; Holder, B.B.; and Olson, R.D. Carr Document No. -- A-1385 Microfiche No. -- A409 A11-B01 H. 1980. Long Term Hazards of Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans. Huff, J.E.; Moore, J.A.; Saracci, R.> and Tomatis, L. Carr Document No. -- A-2517 Microfiche No. -- A638 D02-E07 C09622 Carr. Goodsqn 5 Lee.R C. Chloracne Page 7 <r I. 1979. Toxlcopathology Characteristics of the Halogenated Aromatics, McConnell, E.E.; and Moore J.A. Carr Document No. -- A-2262 Microfiche No. -- A597 G05-0598 A04 J . 1979. Environmental Chloracne: Update and Overview. Taylor, James S. Carr Document No. -- A-1918 Microfiche No. -- A556 A08-BIO K. 1978. Chloracne and Associated Health Problems in Manufacture of 2,4,5-T. Suskind, Raymond . Carr Document No. -- A-2265 f Microfiche No. -- A598 E07-El2 L. 1978. Medical Problems Raised by the TCDD Contamination in Seveso, Italy. Reggiam, G. Carr Document No. -- A-0265 Microfiche No. -- A91 C5-E6 M. 1978. Chloracne and General Clinical Symptoms in a Group of Subjects 0-14 Years of Age Exposed to TCDD in the Area of Seveso. (NJ.H. English Translation) Favaretti, G. Del Corno; Caramaschi, F.; Giambelluca, S.E.; Montesarchio, E.; Marni, E.; Bonnetti, F.; and Volpato, C. Microfiche No. * G783 E10-F10 N. 1973. Chloracne from the Accidental Production of TCDD. May, G. Carr Document No. -- B-277 Microfiche No. -- G2952 C05-C12 O. 1973. Severe Acute Chloracne. A Mass Intoxication by 2,3,6,7 TCDD. Goldman, P J . English Translation. Carr Document No. -- A-885 Microfiche No. -- G679 A02-A14 f. P. 1971. A Health Survey of Workers in a 2,4-0 and 2,4,5-T Plant with Special Attention to Chloracne, Porphyria Cutanea Tarda, and Psychological Parameters. Poland, A.; Smith, b.; M etter, G.; and Possick P. Carr Document No. -- B-958 Microfiche No. -- B253 D03-E03 * Q. 1962. Chloracne from Marketed Herbicide. Goldstein, D.W. Carr Document No. * B-1475 Microfiche No. * B379 G02-G13 R. 1957. English Translation of Berufliche Akne durch Chlorierte Aromatische Zykliche. Kimmig, J.; and Schulz, K.H. Carr Document No. -- A-1635 Microfiche No. -- A499 B08-C07 CO9623 V . ' *i Carr. Goddson & Lee, R C. Chloracne Page 9 j . x: VI. CONFOUNDERS A. The following chemicals are also known to cause chloracne. 1. Chlorinated napthalenes These are heavy petroleum distillates with attached chlorine atoms. Such compounds, sold under the name Halowax, were widely used until the 1950's when they were replaced by plastics. Today they may still be used in electrical insulating and fire resisting materials, sealing compounds, crankcase additives, penetrating oils, plasticizers, and protective coatings. (1983, A). 2. Polychlorinated Byphenyls (PCBs) At one time, these chemicals were widely used in many types of industry because of their stability, resistance to acids and bases, and excellent dielectric properties. Over 209 PCB compounds are in existence. Some past uses for PCBs include: hydraulic fluids, gas turbine lubricants, and plasticizers; and use in the manufacture of adhesives, textiles, surface coatings, sealants, printing and t photocopying chemicals, and fire retardants. In 1976, the EPA banned the use of PCBs In all but totally closed systems such as capacitors. In 1978, NIOSH estimated that 12,000 U.S. workers still had potential exposure to PCBs, chiefly in the manufacturing and repair of capacitors. In 1983, it was estimated that 95% of the capacitors on telephone poles still contained PCBs. (1983, A). C09 625 i\ Carr. Goodson & Lee, R C. Cnloracne Page 10 c r :' SUdjc. ^ 1 r *'~` ,S- c( .;...L.JutAi In i960, 1,057 Japanese were poisoned by the inadvertent contamination of rice oil with PCBs and polychlorinated dibenzofurans. Ninety percent o fth e se people developed chloracne, as well as other effects of systemic poisoning. (1983, A). 3. Pentachlorophenols These chemicals are widely used in the wood preservative industry. Although the pure form of the chemical does not cause chloracne, the chemical is often contaminated with chlorinated dioxins and dibenzofurans, both of which a re ^ powerful chloracnegens. (1983, A>. 4. Azobenzenes and Azoxybenzencs These chemicals are intermediates formed in the manufacture of herbicides from 3,4-dichloroaniline. (1983, A). 5. Poly-Brominated Napthalenes, Biphenyls, and Dibenzofurans These chemicals have caused chloracne in experimental animals. Poly brominated biphenyls have also caused chloracne in humans systemically poisoned by their mistaken addition to cattle feed in Michigan in 1973. (1983, A). B. Other Skin Diseases That Can Be Mistaken For Chloracne 1. Tropical Acne Tropical Acne is a condition which bears a relationship to exposure to tropical climates. The problem of severe tropical acne arising during service in the tropics was first clearly recognized during World War 11. As with other forms of acne, black soldiers were much less susceptible than were white soldiers. During the Vietnam War, there was little general agreement on the cause of tropical acne. Some dermatologists felt that exposure to oil and grease in motor pools was significant, whereas others thought that cooks and kitchen personnel were at special risk. Most dermatologists agreed that persons with significant pre-existing acne were more likely to develop tropical acne than were those persons without pre-existing acne. The condition was found to be aggravated by the soldiers' wearing of packs and C09626 Carr. Goodson Lee. P C. Chloracne Page 11 C m\o - ------ - ^ n . __ web gear, a practice which inflamed the lesions on their backs. No form of therapy was effective, and medical evacuation from the tropics was the only effective form of treatm ent. The incidence of severe tropical acne in Viet Nam was never determined, but there is nothing to suggest that this disorder was significant. (1977, Skin Diseases in Viet Nam. Allen, Alfred.). 2. Oil Acne This condition is caused by exposure to heavy oil and most frequently * effects machinists who use insoluble cutting oils and workers in coal tar plants who handle heavy coal tar distillates or coal tar pitch. The affected areas of skin include the extensor surfaces of the arms and thighs and areas which are typically covered by oil soaked clothing. Comedones are invariably present. Later, pustules appear. Other workers who may contract oil acne include: auto, truck and aircraft mechanics, roofers, oil well drillers, coke oven workers, petroleum refiners, rubber workers, and road pavers. (1983, A). 3. Cosmetic Acne This condition can be caused by covering tne skin with moisturizers, creams, and vaseline type hair preparations. (1983, A). 4. Ultraviolet Acne * This acne can be caused by exposure to ultraviolet light. (1983, A). 5. Acne Mechanics This condition can be caused by local pressure, friction, rubbing, squeezing, and stretching. Dr. Kligman describes the rubbing of the baqk against seat covers as an occupational source among truck drivers. (1983, A). 6. Medication Acne Acne can be caused by certain medications such as corticosteroids. (1983, A). C09627