Document ppqwyj6ML0gQK0qJV2B1KJ9Kj

NCtO CD inI o So MO8 o3 u Ci *-* ocu bO. o 55 V<. < 5HK5 O*4 oM ODHQO0K ow W fr. 2 <y o2 fe ors uo u< SS os < O3c: h mrt" ****- *i. i-*-n'Tyr**'T*'I'^ v K ; *- -, vi ;.".V. -,.iT .u BISt , 'r *\ :y " V" " J v ^ 1 ;?! I'.-? h `i ; 4 *\i i }?* %i I f e " : ' t J ^ l & a JlfcfcK . ? - f e t ,: !. 4 . : :..'.... s ;u3riii " li<j ""i'i " " 3 !0 " ^ s ">P a {i 3 a -uy u 3 q l Pago 2 Part I During tho years Cron 1965 through 1969, a chemical plant producing herbicides - pontachlorophenol and 2,4,5-trichlorophenoxyacctic acid derivatives - reported a mass outbreak of acno chlorina. The number of persons stricken 73 is one of tho largest ever recorded. Furthermore some of cur patients vero also stricken by a complete intoxication manifested by liver* lesions by a deficiency in porphyrin fat and protein metabolism and by nervous and physical changes. In tvo cases# tho i n t o x i cation was fatal. This part of the research will deal primarily with skin symptoms and tho Internal and neurological changes will be discussed in a subsequent work [23] and in more detail in another work [32]. The acno forming dermatoses are caused In most cases by crude oil derivatives - known as acne oleosa - and less often by tar and its derivatives - In these cases It is acne picea. In contrast to those acr.es acne chlorina Is relatively very rare because It is only caused by a small number of certain chlorinated hydrocarbons which are produced and used only on a limited scale. Acne chlorina also differs from other acne forming dermatoses by its localization clinical picture and course. Mass occurrences of acne chlorina have been recorded during several tine periods which are separated by decades# in accord with industrial and chemical development and with the gradual introduction into production of new chlorinated hydrocarbons. The first cases were described by Kerxheimer [18] in 1899 in the electrolytic production of sodium chloride and sodium hydroxide from brine. Kerxheimer assumed that the illness was caused by the inhalation .of chlorine and by its excretion through membranes and he therefore named the disease acne chlorina, i.e., chloracne. The French authors Thibierge [43,44] and Kallopcau [16] were of the same opinion as to the incidence of this disease. Further more, Ilallopeau thought that the black coloration of the comedones r -9 F|5*V sir" i-vv h- : r" ' iO r-- A % t' hL>_-' .j l! *11 * '4 Pag 3 was caused by son lead compound that formed on tho chamber's lead wall* a* a result oC a reaction with chlorine. Renon [351 also connected chloracne with lung tuberculosis in one of his patients and ascribed both diseases to gaseous chlorine. However, Itirsch [20] concluded in that same year that the cause must be a solid substanca which formed on the anodes during electrolysis because exposure to chlorine gas alone did not cause the disease. This finding was supported by Bettmann [2] who ob served 21 patients who were engaged in the production of hydro chloric acid and who were in contact with chlorinated tax coo- pounds'but not with chlorine gas. Lehmann [26], in 1903/ concluded that the actual causes of the disease were chlorinated products such as hexachlorobenzene/ pent*-- chlorobenzolc acid and hexachloroethane which formed on the car bon anode during electrolysis. Because similar cases of acne chlorine were also observed in the production and processing of pnltrochlorobenzene, W. Lehmann [27] concluded that acne chlorine was caused primarily by chlorobenzenes. As soon as carbon anodes ri were replaced by magnetite anodes, the incidence of acne during p f electrolysis ceased. Before World War I, Kahle [46] observed acne chlorine in two 7sra chemists which was probably caused by a chlorine compound - phenylene dioxide - not identified or known in more detail at that time. u The next wave of the disease's incidence occurred at the end r of World War I during the production of chlorinated naphthalenes r or perchloronaphthalenes. In this* period the disease was given an additional new name - Pernakrankheit (Wauer [42]). Chlorinated naphthalenes and diphenyls with a waxy consistency, also known as i halovaxcs, have some very valuable properties such as waterproof- r.css, flame resistance and acid resistance. These properties : earmarked these materials for thae production of protective gas masks and other military equipment. e. A new increase in the incidence of the disease occurred in " [: the nineteen-twenties during the use of chlorinated naphthalenes F 1 i i r t: as an Insulating tutorial in the oining industry (TelcJcy [421). Acne chlorina also appeared in the electrolytic production of chlorines when insulating coatings of tar wero used. This fact brought about numerous disagreements and questions as to whether tho disease in those production processes was not actually acne picca. On the other hand, TelcJcy supported the contention that the tar acne could be caused by chlorinated hydrocarbons contam inating the tar. The excellent dielectric properties of the chlorinated naphthalenes ("haftax", "ha lowax", "nibrene") led to their vide utilization in the production of cables and condensers and another pass occurrence of the disease was produced in the nineteen-thirties when the U.S.A. and other countries recorded hundreds of stricken individuals. Boltzmann [22] also noted the occurrence of acne among the fanily members of workers employed in the production of. condensers. These family members handled and washed work clothes contaminated with the chlorinated naphthalenes. Based on these observations, Boltzmann corrected his previous original, conclusions and stated that the chloracne was actually tar acne and judged the effect of halowaxes to be that of an external acnegenic cause. Ormsby [31] observed acne chlorina with the use of a fungicide used in the impregnation of lumber (sodium tetrachloro-o-phenyl- phenolate). Jones and Alden [24], Schwartz [39] and later many others also observed total disorders in their patients and Flinn and Jarvik [8] noted a death due to yellow liver atrophy. Xn 1938, Kaycrs and his ccworkers [28] were unsuccessful in clarifying the mechanism of occurrence of deroatitides and acne chlorina in their patients with the aid of epicutaneous tests - the tests were nega tive. During World War II, chlorinated naphthalenes were used for the impregnation of ships* hulls when it was discovered that these substances could protect ships from damage of magnetic mines. The use of halowaxes increased significantly, especially in the elect!-- cnl industry. American authors gave acne chlorina another name. Paga 5 bccausa of tha occupation (cable production) of the 1 and coworkers [141# Schwartz (40) # Morris (29)). massive outbreaks of ocno and several deaths were :er World War II, the incidence of acne did not sub- r ho undesirable experiences with the chlorinated lid not prevent their use in the electrical industry An interesting observation was recorded by Harzberg He observed seven cases of acne chlorina in patients ;ed chlorinated paraffins in the form of a food bis prompted Herzberg to conclude that acne chlorine .er the internal ingestion of chlorinated hydro.larly, Fuchs [9] also noted the affliction.of three .heir mothers after they had eaten potatoes fried in Hinkler (48) recorded 10 cases of dermatitis and m e chlorina among 23 workers in a condenser factory 'ene in the production sequence. From these cases .ded that "chlorinated hydrocarbons cause the formaits that in turn cause an1increased secretion from .ands". In 1949 Gavrilova [10] warned of the photoeffcct of polychloronaphthalenes.* In recent years, replaced chlorinated naphthalenes in industrial use* .y the production of sodium hydroxide may be a source .na, V.'e have observed more cases between 1950 and m causes of acne chlorina in these cases have been an of chlorine gas with the hydrocarbons in the .tar -ttings on the electrolytic containers and tubs and ral oils which were used to protect the electrode ; authors noted several cases of acne chlorina. among rkers after the use of nibrene in the electrical le 1950fs. jre, the acnegenic effects of the mineral oil based es used in metal working increase when chlorinated ire added. Therefore, some cases of acne oleosa were t exhibited a partial acne chlorina character (sore rrutho Jos. song veral da ion d d thors ge to dif i.e. , i 9 :ed > ? ib- acne t L957 so l id phenol to 1 tr-- -A. V-t" c-- I*. i.- I i - i! A u^JugAUJ^JUimaK! t-H;ii.lU-A Page 7 disorders of tho liver, kidney, myocardium and nervous system. j The author described the death of a patient from necrosis of tha pancreas as a special ease. Furthermore, he also observed i dermatitis in a nurse who had had contact only with experimental i i i animals. Finally, he diagnosed acne chlorina in tha fourteen i year old son of an employee whose disease was contracted only from tha household environment - by wearing his father*a con taminated scarf and by using his father's towel. Actual observations . The process called FCP (pentachlorophenol) which caused mass damage in Czechoslovakia was, as far. as production is con cerned# identical to the process from which Kimaig and Schulz drew their patients for observation. The final products of this process were sodium pentachlorophenolate, 2,4,5-tricholorphenoxy-. acetic acid and the latter's sodium salt and butyl ester. 21m primary raw material was technical grade trichlorobenzene which was produced in a neighboring building for the production of hcxachlorocyclohexane (HCH) and lindane. .The table shows the entire production scheme (Table I). The chlorination of trichlorobenzcne produced tetrachlorobenzene and hexachlorobenzene. Sodium pentachlorophenolate was formed by the alkaline hydrolysis of hexachlprobenzene. Sodium trichlorophenolate was produced by the alkaline hydrolysis of tetrachlorobenzene. The hydrolysis of tetrachlorobenzene with sodium hydroxide in the presence of methanol took place in an autoclave at 190*C and at 45 atm of pressure for one hour. After cooling, the methanol was distilled from the hydrolysate, the hydrolysate was diluted with water to a 251 concentration and it was then syphoned into a storage tank. The condensation of sodium trichlorophenolate with monochloroacetic acid produced sodium trichlorophenoxyacetate. Following cooling# centrifugation and flushing with water, the dried sodium trichlorophcnoxyacetate was picked out by hand and placed in small barrels. Some of this product was used to produce the butyl ester of >,1 C*, trlchlorophcnoxyacetic acid. This production took placo In another building The production of both tha primary products took placo in a four story building with grated floors (WEMA grates) which was * one reason why the entire building was contaminated with the high risk substances. The building was not sufficiently airtight# the local exhausts were in most cases improperly installed and hemetization and mechanization were insufficient. Initially# the sodium tctrachlorophenolate [sic] was escaping from the centri fuge into the work space in the form of a mist. A series of tasks such as the removal of solid substances and the pumping of * liquids were performed by hand. The workers were dressed in linen work clothes. The thorough cleaning and frequent changing .* of the work clothing was impossible to guarantee over the entire interval of production. Rubber gloves and respirators were used at some work sites. The conditions surrounding the production of the butyl ester of trichlorophenoxyacetic acid were the same as those described above. Kimoig and Schulz [25] found that the main source of acnegenic hydrocarbons was that segment of the production process in which sodium trichlorophenolate is formed by the alkaline hydro lysis of tetrachlorobenzene in the presence of methanol. A covorker of these authors# Doctor (of Chemistry) Sorge# had de duced on theoretical grounds that if this reaction were conducted at 199#C and 45 atm of pressure# chlorinated hydrocarbon by-pro ducts such as polycfclorodibenzo-p-dioxines, polychlorodibenzo-- furans, polychlorodiphenyl ethers and polychlorodiphenyl oxides may be formed in snail amounts (Schulz [36]). Sorge also pre pared sens of these substances by his synthetic process. Animal tests carried out by the authors (Schulz and Kimalg) with tetrachlorodifcenzofuran and 2,3,6,7-tetrachlorodibenzodioxine have proved an extraordinarily high toxicity for these substances. A simple smear of a 0.1% solution of tri-- and tctrachlorodibenzo-- furan on a snail area of a rabbit's auricle caused heavy liver* Paga 9 clonage and death of the test animal within 2 to 3 weeks (Schulz (3 6 )). 2,3,6,7-Tctrachlorodibenzodioxine, which also has very strong nenegenic effects, was proved to be far more toxic. Only then was Dr. Serge successful in the identification of this enormously toxic substance in the production process and in the final product- He proved that this toxic substance is forced only at certain temperatures and pressures. If during the alkaline hydrolysis of tetrachlorobenzene to sodium trichlorophenolte the temperature is reduced below 153 *C, the toxic substances do not fom. However, at this low temperature, the reaction tine is extended from one to five hours and the productivity is ob viously lower. Furthermore, it was proved that the condensation of two molecules of trichlorophenolate to give tetrachlorodibenzodioxine is an exotheraic reaction. Several explosions of auto claves with injuries and the lethal intoxication of workers were reported to be the result of this reaction in the German Demo cratic Republic (East Germany) (Schulz [38], Goldaann [11,12]). Tetrachlorediber.zodioxir.e was also identified ia the Czechoslo vakian production process and in the products as well. The first two cases of acne chlorin were noted in 1965 in; two technicians who operated the production machinery. It was as sumed at that time that these two cases were caused by careless work and an undeveloped production technology under seniproduction conditions. After one year without a reported case and during which production was temporarily halted, a mass outbreak of 78 cases was recorded within the following three years. Finally, after a detailed investigation and study of the entire problem, the process was terninated and production ceased in 1968. Workers .from all stages of production were stricken. At that time, it . was impossible to determine which production stage was the most risky because most of the workers were involved in several stages at various locations in the plant within a relatively short time. Workers directly involved in production as well as maintenance per sonnel and workers digging sewage ditches were stricken. Later, ,a research scientist working to isolate the acnegenic ballast *IT-a.4'---K4.**. '3 f-'-rvi fr h.r ( t- t - -j Page 10 substances iron the products of the individual production phases was even stricken. His research work was carried out outside the production plant in a research institute's laboratory. In addi tion to the 78 patients with dangerous symptoms of acno chlorine or porphyria, other workers in this plant had symptoms of acne which were, however, synptoas of juvenile acne or of a similar * character and could not therefore be counted as an occupational disease. With the exception of two female laboratory technicians/ the patients consisted of males from 18 to S7 years of age (4 persons below 20, <6 persons from 21 to 30, 11 persons from 31 to 40, 10 persons from 41-50 and 7-persons from 51 to 57). Therefore, the acne chlorine patients were mostly young people. On the other hand, more than half the patients with porphyria cutanea tarda were older than 40 years. Generally, the disease followed a normal course as described by other authors. In only six patients did the disease'begin sud %denly'as acute solar dermatitis, i.e., by erythrema and edema in regions exposed to solar radiation and continued by acne sym ptoms (Photographs 1 and 2), as observed by Goldmann [12], Grimmer 115], .Braun [6] and before these authors, also by Touraine and co workers [45]. Therefore, chlorinated phenols in some cases have similar photodynamic effects as the chloronaphthalenes described by Cavrilova [1C]. Erythema and edema in these patients were obvious mainly on their auricles. Sometimes, small blisters in thick groupinys were observed there. In all the other patients the acne developed slowly. Among the less severe cases the disease was limited to single or densely grouped comedones, ccr.ditoned by follicular hyperkeratosis, which were so small and sometimes so numerous that they appeared to be a slate grayish-brown color,, like dirty spots on the skin. These symptoms were noted mainly on the face, with maximum occurrence above the cheek bones (Photograph 3) . In the more severe cases^ the comedones gradually developed into small white cysts similar ` > i .r > ..r.jv.uanw-1 iim,-- mirrr*--~-it*~nnr*'Mi i Pag 11 to nllia, although with black centers, and Into largo cysts ranging froa the siro of a pea to that of a nut (Photographs 4, 5 and 6). As opposed to other acne forming dermatoses, the described symptoms and manifestations mainly lacked signs of an infection. Only In the more severe cases and rather in the vici nity of large cysts were some reactive inflammations, infections, and abscesses noted* The emptied cysts and abscesses left behind large atrophied scars with raised edges and with bridges of intact skin under which a probe could be inserted (Photograph 7)* This basic clinical picture was supplemented by diffused hyperpignentatioa in the face and by papulopustules on the torso and ex tremities* Patients who were found to suffer froa a disorder in porphyrin metabolism had symptoms of porphyria cutanea tarda in regions exposed to the sun (hyperpigmentation and hypertrichosis, blisters, excoriation and small scars). However, in this groigt there were two patients with prophyria but almost without any acne at all* Histological investigation is not much help in diagnosis. The symptoms begin with hyperkeratosis at the south of the follicles After one to three weeks, the follicle changes into a cystic for mation filled with a h o m y substance [keratin?] (Photograph 11) and to'a small extent with sebum. However, the epidermal changes are small. After the rupture of the full follicle, the contents of the cyst penetrate into the surrounding tissue and a granulosa of foreign bodies forms around the area (Photograph 12) * . The disease normally starts on the.face above the cheek bones. However, in 17 patients the disease started in an unconventional manner by papulopustular eruptions on the extremities, primarily on the lover extremities. This characteristic, resembling* more acne oleosa, remained in some of the patients for the entire dura tion of their illness. The most common localizations of acne chlorine were the cheehs, temples and to a lesser extent, the entire face." Eyebrows, eye lids, the perioral region and the scalp and hair area remained free. 1 " e rj * Page 12 Other prcdilccted areas were the auricles, the back of the neck, the back and the chest in a seborrheic localization and the genitals. The auriclos and .genitals and especially the scrotum were stricken by the formation of large cysts (Photographs 8 and 9)* Among tha five most seriously ill patients, the disease spread * all over the body and had a discouraging effect that was heightened by the disease's usual persistence, the long term healing and by medical helplessness (Photographs 10 and 7).* The contents of the cysts produced a repulsive and rancid odor. For some of the 'patients the disease disrupted their social and family relations and caused severe depressions. Some authors, such as Braun [6], emphasize itching as the initial symptom, but we noted this symptom in only three cases. In 20 patients with extensive symptoms, the occurrence of pustules, cysts and abscesses was also noted in axillae although this location was not mentioned by other authors. Because of the great number of follicles in the axillae and the similarity of the axillary skin to that of the genitals and for several other^ reasons, this finding appears to be just as valid as localization on the genitals and the genital area. On the other hand,' it is surprising that acne chlorina does not strike at the hairline or scalp'. In the case of one patient, the acne symptoms disappeared in the facial areas when he grew a full beard while in other areas, the symptoms continued without a reduction in intensity. So far there is no explanation for this phenomenon. Hypertrichosis or hyperpigaentation or both were determined in the faces of 19 patients without a laboratory diagnosis of a deficiency in porphyrin metabolism. Bloiberg [3] made similar ob servations. These symptoms receded simultaneously with the healing of acne chlorina. Wore younger persons suffered from acne cfc\lorina than older persons.* This study group contained 50 persons (85%) below 30 __ __ `Translator's notes Beginning of this sentence illegible. j j j 4 ; j j Pags 13 years of age. However, this fact cannot bo used as a hard and fast rule or to support tho findings because tho production plant under study employed mostly young workers. The preillness medi cal history among the patients did not indicate any significant predisposing factors and no incidence of serious illnesses, intoxi cation or etiolation*. Furthermore, no relation to hair color, eye or complexion color, to the degree of body hair, to the per spiration of skin oils or to hereditary follicular hyperkeratosis and other skin'diseases was noted. Only one patient reported a more severe prior case of acne juvenilis, 12 patients reported mild cases during puberty and 14 patients reported only insignificant acne juvenilis symptoms. 18 patients also had some infrequent con tact with mineral oils either during the appearance of the symptoms or at some time in the past. ' These patients were mostly involved in maintenance work as mechanics. However none of them had ever had an oil acne in the past. Their illnesses following contact with tetrachlorcdibenzodioxine were of the same character as the illnesses of the other patients. Their diseases were not similar _ to acr.e oleosa either in appearance or in localization. The latent period from the initial contact with the risk substance to the appeamace of symptoms was quite varied. Soane workers became ill after exposure of from several months to several years and the disease in their cases was rather mild although the indications pointed to a massive exposure. In other cases, severe damage occurred after a very short time of several weeks and after an apparently snail exposure. For example, one of the cost seriously ill patients worked under the semiproduction conditions for only two and- a half weeks before the outbreak of the disease (acne and porphyria cutanea tarda) After that he had no contact with the risk materials. It is not clear whether individual predisposition or the level of personal and work hygiene is more responsible for the Intensity `Editor's note: This nay be a dubious choice. The Czech "etylismu* transliterates to "etilisa". Paga 14 of danaga or latency of the disease. Most authors discount Individual prodispositon. However it is believed that the deciding factor must be the degree of actual exposures which is undoubtedly dependent on a series of other factors such as work discipline, personal discipline, adherence to preventive measures, frequency of changing work clothes and undergarments, the degree and regularity of hygienic decontamination, work site order and cleanliness, dust in the environment, etc. . These patients also had a series of subjective difficultiess tiredness, weakness in the lower extremities, muscle pains, sleepi ness and insomnia, increased perspiration, lack of apatite, head aches-and. other disorders in the mental and sexual spheres. These complaints were more recurrent and more intense in patients with the more extensive skin symptoms. In more serious acne cases, a. significant weight loss was also noted. It is our opinion that all these difficulties and symptoms are manifestations of a rather overall intoxication than of only the acne chlorina. All the patients were admitted to a dispensary. Regular examinations of their dermatological, internal and neurological conditone vere arranged. The patients who were still working vre transferred to prevent further contact with any acnegenic factor. All contact with chlorinated hydrocarbons of any type was prevented even with those substances whose acengenlc effects have not been thoroughly proved. Furthermore, all contact with mineral oils and tar and its products were prevented. The application of mineral bared ointments was discounted for external therapy. The plant's medical doctors were cautioned against prescription of any internal medication with an acnegenic effect (iodine and bromiu m preparations corticoids and others); The patients were given detailed medical directions concerning their daily regimen, perso'nal and work hy giene and secondary disease prevention and treatment. All available medications for acne were utilized in the treat ment. The expressions of comedones and the pressure relief of the contents of cysts and abscesses necessitated many periods of Pag IS hospitalization find special ambulatory treatment hours attended by a specially trained nurse. No special results were observed as a result of repeated hospitalization. The best results were noted after the expression of comedones by the use of a sauna constructed for the patients by the factory on the author's re commendations. It was not possible to test the effects of vitamin A acid (retinoic acid) which has been praised by some authors in the medical literature. However, in agreement with the findings of other authors, it was determined that no local or internal medication exists which has an effective and permanent healing effect on acne chlorina-. Some of the patients have been under observation for eight years and their disease still persists* Or. Schulz's 33] patients have manifested continuous symptoms for more than ten years. Goldmann [11] has now been treating on patient with comedones and cysts on his penis and scrotum for 18 years! In most of the patients discussed by these authors, the symptoms and manifestations of the disease progressed and reached a maximum after about one year, even after transfer of the patient from the high risk work area. A regression takes place after t w or three years at the earliest. In some isolated cases, the pro gress of a mild course of the disease was observed even after five years. However, the regression of the disease in all the patients was very slow and, it may be said, even lasts a number of years. Of the 78 patients treated by the authors, 76 suffered from acne chlorina. Of these, 11 simultaneously had hepatic lesions with a deficiency in porphyrin metabolism. Two patients did not have acne chlorina. One of these two had porphyria and the second one died in 1966 from acute intoxication. Pentachlorophenol was considered to be the cause of death in that instance. When the toxicological analysis was carried out at that time, the investi gators were unaware of tetrachlorodibenzodioxine and, therefore, it is our contention now that in that case, this highly toxic substance was primarily responsible for the acute intoxication. Combos [13] mentioned one patient with acne chlorina and porphyria in connection with this production process. The authors analyzed 55 patients internally and neurologically in detail About half of these patients had a deficiency in lipid nctabolism and in norc than one-third, some minor biochemi cal deviations and mild hepatic lesions were noted in the first stages of the disease. In 17 patients, the authors found symptoms of central nervous system disorder, the majority with lesions of the peripheral neurons of the lower extremities (verified by EMG examination). In most of the patients, physical disorders, pri marily an acute neurasthenic syndrome', were diagnosed. In addi tion to the death due to acute intoxication (pentachlorophenol? tetrachlorodibenzodioxine?), three more patients died. In one * patient, the porphyria developed unusually rapidly into an arteriosclerosis of the brain with an atypical morphological diag nosis and demention. Two patients died from bronchogenic carcinoma. All these patients with their complete symptoms are discussed in other papers [32,23]. Discussion In agreement with Kimnig and Schulz, we cite the tetrachloro dibenzodioxine which is formed during the production process as the main reason for the skin symptoms as well as for all the other deficiencies mentioned ar.d diagnosed in the authors* patients. This toxic compound was confirmed in considerable quantities in the final product (Arboricide E50), in the butyl trichlorophenoxyacetate and also in the mortar and wall paint of the factory building. Even adjacent rooms such as worker dressing and locker rooms v;ere contaminated with this compound. Test rabbits placed into these rooms soon died. In his monograph, Braun [5] cited the following chlorinated hydrocarbons as the then known causes of acne chlorina: chloro- ** benzenes with various degrees of chlorination, chlorinated-phenols tsodium tetrachlorophcnolate, pentachlorophenol) , para-nitrochlorobenzene, sodium tetrachloro-o-phenylpher.olate, chlorinated Pago 17 naphthalenes, various chlorinated diphenyls, trichloroxydiphenyl, chlorinated diphenyl oxidc3, sodiun o-(2-chlorophcnyl)phenolate and others. However, Kimnlt and Schulz [25J ascertained that pure pentachlorophenol and pure 2,4,5-trichlorophenoxyacetic acid do not have any acnegenic effects. Therefore, they checked the presumed effects of the other substances that were blamed for causing acne and found that neither pure nor chlorinated benzenes (from 1 to 8 chlorinated positions) nor chlorinated diphenylethers have any acnegenic effects. A definite acnegenic effect was proved only for the following substances: chlorinated naph thalenes (5 and 6 chlorinated positions) in agreement with Shelley and Klingman [41], higher chlorinated dibenzofurans (diphenyl oxides) and 2,3,6,7-tetrachlorodibenzodioxine. Therefore, it is possible and even probable that some chlor inated hydrocarbons that have been previously considered to have an acnegenic effect do not have this effect and the actual causes were other ballast chlorinated hydrocarbons contained in those hydrocarbons. Tetrachlorodiphenylene oxide (tet'rachlorcdibenzofuran) 2,3,6,7-tetrachlorodibenxodioxine (tetrachlorodiphenylene dioxide) In an animal experiment, Kimnig and Schulz found an ex ceptionally high toxicity for tetrachlorodibenzodioxine. In a local application on rabbits' auricles (keratosis test) , this com pound produced a strong reaction even at a concentration of 0.001%. Also, a skin application of this substance at the same concentra tion produced acne chlorina (Schulz (38]). Tetrachlorodibenzofuran was proved to be 10 to 20 times weaker. Chlorinated naphthalenes had a thousand times weaker effect. Generally, acne chlorina is K caused by the direct contact of tctrachlorobenzodioxine with the skin. Absorption through the skin is not ruled out and an effect ws m fcw esT* K: i-'rv f: rKM 'X-i * r: t Paga 19 through the ingestivo or respiration tracts is also concaded. However, in a pure ingestivo experiment with a test animal, acne chlorine did not occur. However, the cases of acne chlorina con tracted after the ingestion of chlorinated naphthalenes as food fat substitutes should not be forgotten [19,91- Tetrachlorodibeozodioxine used internally has a strong hepatotoxic effect. A dose of 20 to 50 ng per kg of rabbit's body weight causes death in all the test animals by yellow liver atrophy. Because of this enormous toxicity, all the preventive measures taken at the high risk processes In East Germany and Czechoslo vakia were proved to be completely ineffective. The only de pendable solution to that problem was the reduction of the re action temperature and pressure during the alkaline hydrolysis of tetrachlorophenol&te to sodium trichlorophenolate. In East Germany, the- decontamination cost of the high risk areas and buildings was extremely high. One chemical plant attempted to use for other purposes a contaminated building which had not been decontaminated after the building had remained unused for two years, but new cases of acne chlorina were shortly reported. With normal decontamination procedures new outbreaks of the disease occurred and therefore, decontamination had to be carried out using special pressurized chemical protective suits with pressurized breathing 'apparatus because gas masks were not sufficient. Doors, windows, the wooden trim and other wooden building components had to be burned; the steel construction materials in the building had to be sandblasted; the plaster, facade and floors had to be torn out and cast into cement blocks together with the tubing, plumbing and other equipment. These blocks were then transported to the Atlantic Ocean and sunk. The disposition of those non flammable materials by burying would have run the danger of con taminating the subterranean water supply. Only the most expensive. components, autoclaves and some valves, were successfully decon taminated by repeated washing with special detergents. The Czechoslovakian plants are still closed and their fate is still undecided. The patients are still under a continuous ob servation. Referencos 1. t i t i t r , C. * i r , ti. p 3-*iirtl . loloucatM^a d w la |*rftUCblorpbr^eL lod. *!eJ. S ur*. 7J, 1711. a. 7 . -- 2. CrtUM AX Cltlcr-Alut, rio* Urt3.icre Fcna rea j Jo i wk'IUt fhwk. cwrd. W*Ur,, i?. 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X r u ZcUwcnXs aVula Q ilc n s a tfc n b TxS- *j i jAa wi J u u a s t y s X taaiU U (ASAX 7. 1SJZ. . 12--IX -- IX " `.O r U m ia , P. p Scbwarsla a b t a Cbtoa. **Va, cln UuicBintaxiViL*a d a rtt X X * 10. 7T^Uscb!3:lltMlai," , ' t * H -rJ7 .1 V -Jt?- X ---*7 :cbU*X Av Th K m A-rorpliy caito* Urd 7 r rl v/reba c)fcc!tfck i ; vfljri;or. RrsL K LMt o ix -- jx i;*ix Ck. c . k i an a (.ciV'a m Sypu lO ik s io U IX M* -- IX CrLunsr. IU A lo e durch cfcloricrii t kto.'fc. ZfcL Arlre 73. -- IX Iltllejicia. J Sen. med. 1CJX - 7JI 17. !lcr;(. Ufu O s t e a l ferene, tud P lk trlT ,. A i -- U. UentEtccr. 1 Uach. eed. V7kdtr^ 3Icr?L=r X U rM W Jtl cU cr^rn ca r.T 'R a . Dr . 15:7. t . <25. -- 20. C i r a .la c h c r F ttltc zar ele* erecucuet- Curt, d. Zc li^V.'uiiIJbiLuicrlthlu- _ -- ClL C rea X -- 2L tle /c jx a TItS V&rlr. VVcrlcriic.Xrirrrmr, Ca D-.'-rthera. 3775 -- clL J-ia tr (JL -- ZX IJo ttrtz r . T CLIcracao u_ r e i a e b r e e x Anch. J ty t, 117. 13X X z. ecurcdena -- rtt t.r a j X -- =X )Ur**X U JlaUaiitJ. J , C r in ; t t . . i-tv ix rx ra jJn v c x X *t U in iu c y * Iihqi2ljj Laj cblaTlua pU i}* 1U-il*Crl>UJi-- pTipJUVtwAaa m,- Pag 19 2L ] n r ^ J. M , /Jer% li. Es Aa a c s d v M dec&jU-riotli. AicX Dnra. SfjiX (ChlM* . cu)* 3X UJX *. 1LI2--lv ll. -- 2X KIouLX U SlIiuU. K. IL DcrutUch AVna (v&f. Cblorakao) durch chto.*lcrLv aronalU cb lylllK ltr Aihrr. OrmuUclca. llX 1C3X . a. 513- 3, -- 20. U ita a w , X. Bu tp erl- .CAleUfi SluJIea fiber de C la lla u tcck* Ifdi . tiycicaitcb wichtlcr C ori . Do* 1c aa dea O rc a i u u XL Sludlaa Qber .CU lonlne*. Are*. H rt* <X 190X * 322-- 33X -- ctu lrica L -- 17. I r b i a c , V Obcf CWorako. Ard. D e ra , 77, 19QX X J G - 2 U . 1'jJdca 3X1--3IX -- 2X KMfet, X X Stlrcrber^ H. Xu S t la u a d i b o a .Tnvltiivc Iro a etpodorc la c e rn a cblarlA* .`led bydrocaxboct. p todaur. Uyt* T co ln l . T0. 19, a. 24I-2SX cll. B nw a X - H Itarrlx, X X T i b u d a v , X tt> Cib la * . radi" -- A cola ea a a c * d r in ^ a ^ tala> ture. J. A acr. a e d . A u , 12X K R . X lt2 -- J iX -- clL Brasa X -- M. O d K 2JU CB*' zikcha 12. ilcrci j iu i o rg lella r t a u c i _ <talt faocbleilicha Cblarkohlcsic&ssenlaC- * lea; la Csra; tn.n Pj:ai-7robcxa. W i* r ^ 2 ^ l a Kcnlerra^ Ds Ddr t Lcltx USX ctt.* .B ic tr <1 --- J t.'* O inulif,1 O uvO X kU T v pcujre'.j*k 7t -- .XX^t. r * i J . r - . . J , Ic L lX C , S)ilU 1 tX 17 n - rdisk, L , Xitbvifc/, J , r X n X X *" A , K ftacati (X 1 ^ I - Mrlbazti! i d r u frUKcH;l pfl frfrolA T ,U J lCJjlOrlc3nxr <"i u j . U i . (v U tbi)* -- tUcctOt rru cd n acA f *-ku (Ib liv a u c u ), r a , 233. 1X7X S. 220-- Cu L o ta llr tu s d lu .; der u : m ) sur vtatela X* X `3370. i . 5 --C7X -- ' (iiluL u f [ x iaall . chbuc; au.'iO d ik u lq o a ;ua.<L-c. eeu isC d, 133X . ''u i -- J.Srbil^ IX.XU ,jicrleie:itLlt Ua*cr>MChwa*t&ur der UiU*racAe. AreX .m, 2B3.3257,s. 2C1--CA -- . E. 1L: Zur kCRsik A ltulaitc ueboc. Arbe-UiULdii^ (ASA!, X 25-- . -- 31. ScLalt. V. 11U O u d ^ l l.' -- 70. SdiK'xrlc. Au DeracatLOa a t p iL :iic r e o t u l c j a A u c a J. .U. HUU, la. 1530 a. SOS--52X -- 4X ^cba-*ru, l u Aa obiLrcok o J U l a n u eme ( u j U c rxfa*| t u s e rU.V'.rlunL J. AiotT. ard. Akt. 122, 1 3 , r. 153. -- . ** U iillrT .tf. X XUacm. A. M Tb* rtp * - lineAttJ jirru c u c i ul e m e !<> pe-ia- aa4 AcueklsrukfJiUleael. Arclu U c n a S J k (n.lr^xo). 7*i 1VS7.%.bi.3. -- <2.TeUd.7', l u Du rcrn-Lk.`*akLcU [C."Ll<wiv.o |. Cita. Wibe, LS. i'JZl, L. SUS--0C4, IUA.-J 13/-- 01. -- O . Tb'Ucrr. Cu Atjv cocaCdo* riltiOc de 1 n n b d a ilc u p ra ln s tc a d - U de cbloiiqcet. Sea. *.'jC3, l 2X CU. Ora S. -- Page 20 R Tli.'.l'r*;. G,, Tj . h.ri. Di.: L'*c-f n`-At Dtr* 1,1.. |r-Tifc|. ivjl'U ili-- tt, -- ch. S. -- I I A , ,, I.Aciras: Icalticderutmu l>jf K .ilt^ /u ij tu llu c . Dull. lo e . L in . * ,P* . 4i. ivjl a. :- s - :> A -- 'J . Wafcl*. r.. Cf.*: 7"Uc taa .CUJiifa^*. IrtkwLW fwl liu. Ui^x'c. 1M. -- c"- liraur 5. -- 47.Water: llc*dllil-c 1Lf.*uH:c durcli lic^i-ricWiUL-.*JswrUtile |rcinjLr&k> Lcll|.ZM. Cna.TttJjf. 1. 1KU. %. VJ3~ CL -- <1. `iVIuUir. Kj L ir CI:!-v (Vk JPer- ?. iL -L G.L-l.Uvt, IL U JL<;*--OL 41 Lace. IL Sc!utt<, TLIC./'u ^IUj Z nrratJULr cn Ici def !krtUii:i ses CU.riLeocl- WdiiJparca. Arele Csctib.*PA*.&L C^ -*1 wtri*.il>*r,,il,Hrfl,s.SiS-- s'A [10] Pathogenesis of photodermatides from chlorinated naphthalenes [13]' Combos, et al., Porphyria cutanea tarda and acne chlorine occurring during the production of cyclic chlorinated hydro carbons. [23] Symptoms of total intoxication in acne chlorine during the production of herbicides - in final preparation for printing. [31] Discussion on paper by Jones [24] [32] Health hazards to workers in production of sodium 2,4,5-trichlorophenoxyace tate. r-t-v 1r* *f--' fi- i J Pag 21 TAKLE I . P r o d u c t i o n Sehet Plant for production of liCH ( h e x a c h l o r o c y c l o h e x a n e ) 1,2,3-trichlorobearen end It* isomer* (1,3,5- and 1,2,40) Plant for production of penta- | - . . f ` i .;L.*.! chloropher.ol ar.d sodiun salt* of iv "***f.*J 'Vr1 trichlorophenoxyacetic acid *! .**/ -- / V . * **. ' `;i>;.*% * : : * * i*.v Vv* a a cl'<' . 1. V I < .!I **' .. , ` ' y r 1,2,4,5-tetrachlorobnxea` Q aa . coth*r V j ( hrranchioroboxen 1-5: H SOd rophenolat -\v.-i : :*j:;T* :**. , V 0* .*.--\-v '._->' ,>/;;v.. t . 'a--;* * ;:.x , ` V*. i'*"' .;,/?>-; *^ : *'- - v > Sodiun salt of 2,4,5-trl- \ - * -.*.'1 *. '''.l.,.PeQt:*chlo^oPhool chloropher.oxyace tic acid I_: *"V`.Z/ ' *_* > `-- `,Y*; < ** a o-a^cnoNm a - O - .. 'I t . I *lant for production f b u t y l . . t . r _ , -s .... aa - - y-is V v ; * - : .... . J .* i . - C l - ; . a - / r ~ V L c u ^ o a a i ^ 3 i ^ i r ^ :it. , * :.Vv' '* ' I : , v ;u .- _ . 7 .. ,- , b u t y l e s t e r o f t r i c h l o r o p h e n o x yyaacceetic acid - <1 h t.