Document RJrJrOVMpqNLbgogBdODo2v1k

Diphenyl Poisoning in Fruit Paper Production A New Health Hazard Ilona Hakkinen, MD; Eero Siltanen, MSc; Sven Hernberg, MD; Anna Maria Seppaldinen, MD; and Pauli Karli, MD, Helsinki; and Esko Vikkula, MD, Tampere, Finland Production of diphenyl-impregnated fruit the agent itself or impregnated paper standard blood cell count. The air con wrapping paper under poor hygienic condi tions caused the death of one man and the poisoning of eight other workers. The di phenyl concentrations in the air had been much in excess of the present threshold limit value of 1 mg/cu m. The clinical pic ture of diphenyl poisoning is characterized , by central and peripheral nervous damage --and liver injury. The cause of death in the fatal case was acute yellow liver atrophy. is handled expose the workers to vari ous concentrations of diphenyl. Few studies on the toxicology of di phenyl exist The lack of data on human poisoning has created the impression that its toxicity is fairly low.- However, as early as 1947 Deichmann and his collaborators'' were able to show that prolonged centrations, however, were low (less than 1 mg/cu m).6 In the fall of 1969, a so-called oil man who had been intensively ex posed to diphenyl for 11 years became ill and died. Since diphenyl poisoning seemed to be the most probable cause, a study of all exposed process workers in the paper mill was carried out. The ' In three of the eight men with poisoning, exposure to air containing diphenyl results of this survey will be reported .. there was histological evidence of liver in in concentrations of 5, 40, and 300 below. - Tjury. Changes in the results of blood analy mg/cu m produced liver and kidney 1 sis cr rcr.a! funch'cn did rot occur. The prognosis of diphenyl poisoning is still injury as weii as bronchopulmonary lesions in mice and rats. Cutaneous Production Methods and Exposure unknown, but some patients showed deteri oration when seen after one year. application also gave rise to toxic Diphenyl-impregnated wrapping effects.3 The authors concluded that a paper for citrus fruits has been manu concentration of 5 mg/cu m in the air factured in Finland for about 15 The fungistatic agent diphenyl is an effective preservative for cit should be considered dangerous for man subjected to prolonged expo rus fruits. It is usually impregnated sure.3 According to other authors, pro years. In the process, diphenyl is dis solved in heated pure paraffin oil. This solution is prepared in a sepa into the wrapping paper; the air space longed feeding (0.5% and 1.0% di rate room, where a special worker (oil between this and the fruit then be phenyl in the food) may result in toxic man) dispenses diphenyl from paper comes saturated with diphenyl va symptoms, ie, inhibition of growth sacks into a mixing container. The ; por.1 Impregnation is usually per and kidney injury.4 mixture is heated to 90 C and pumped formed in the paper mill that manu The clinical picture of human di into a basin connected with the paper factures the wrapping. Diphenyl is phenyl poisoning has so far not been machine. The diphenyl-paraffin oil first dissolved in paraffin oil and then described. The only' data we have solution is then spread on silk paper applied by a heated roller to the paper been able to find consist of a study with the use of a roller at the dry end while it is still in the machine. The from Strasbourg, France, describing of the paper machine at a tempera reels are then printed and cut into transient nausea, vomiting, and bron ture of 90 C. The production of such pieces, packed, and distributed to the chitis in "a certain number of work paper is discontinuous, but has in consumers. All operations in which ers" engaged in impregnating wrap creased over the past few years. At ping paper with diphenyl.3 On the the end of the 1960's diphenyl paper other hand. Weeks and LcntleB were was produced about one third of the Submitted for publication May 5, 1972; accept ed Oct 10. not able to detect any' difference be year. Before a change in the type of From the Institute of Occupational Health, tween 47 workers exposed to organic paper, the diphenyl basin and con : Helsinki (Drs. Hakkinen, Hcruberg, Scpp- reactor coolants (terphenyl and di tainers as well as the pipelines and Slainen, and Karli. and Mr. Siltanen), and . Centra! Hospital of Tampere tFinlandi iDr. Vikkula'. phenyl! and 47 unexposed workers with regard to blood pressure, pul the equipment betsveen them are emptied and cleaned. Cleaning was Reprint request* to the Institute of Occupa tional Health, Haartmaninkatu 1,00290 Helsin monary function tests, serum creati earlier done by trichloroethylene but ki 29 (Dr. Hernberg). nine and urinary protein values, and since 196S tetrachloroethylene has 70 Arch Environ Health/Vol 26, Feb 1973 DSW 345767 Diphenyl Poisoning/Hakkinen et al STLCOPCB4084267 been used. The cleaning of equip ment, which requires one hour, is done by the oil-man five to ten times a Table 1.- Diphenyl Concentrations in Air of Paper Mill Average Concentrations, mg/cu m year. In 1959, the workers had com plained about the strong odor and of irritation of the throat and the eyes. The concentrations of diphenyl in the air were then between 4.4 and 128 mg/cu m (see Table 1). After these measurements only a simple exhaust hood was built over the paper ma chine and a ventilating fan with two exhaust ducts was installed in the oilroom. The next time measurements Sampling Locations - Paper machine hall In front of paper reel Behind impregnating roller Near paper machine Near rolling machine Oil-room -Near measuring container Near mixing container During addition of diphenyl into mixing container Above measuring container (ltd open) Am* 1959 173 128.0 13. - 4.4 19.5 ... -- ... January 1970 7.2 64.0 l.S 0.6 3.5 15.5 74.5 123.0 were performed was in January 1970 after the death of the oil-man. The Tabte'2 Tetrachloroethylene Concentrations During Cleaning of Diphenyl Containers and Pipelines results are shown in Table 1. As can be seen, the exposure of the oil-man had been intensive indeed. This job usually requires about 100 to 105 eight-hour shifts every year. The concentrations were particu larly high in the oil-room when di phenyl was added to the mixing con tainer. Checks of the measuring con Sampling Locations Paper machine hall in front of paper machine roll Near operator of paper machine Oil-room Near measuring container Near mixing container . Breathing zone of oil-man during cleaning Average Concentrations, cc/cu m (ppm) _ January 1970 November 1970 9 30 30 14 75 34 40 . . . . 32 35 tainer with the lid open also resulted in high exposure. In the oil-room, diphenyl occurs both as vapor and Material and Methods ten muscles, maximal conduction veloci dust; in the paper machine hall, pre'domihantly in vapor form. Skin con tact is also likely to produce addition al exposure. In the fatal case de scribed below this route probably played an important role. The oil-man's exposure to tetrachlo roethylene while cleaning the equip A total of 31 men were engaged in the process and they are all included in the study. Six of them were oil-men, 13 were paper-machine workers, 7 were rollingmachine workers, 4 were handling residue mass, and one was a maintenance worker. Two additional workers were included in the study because of suspected poisoning: ties (MCVj of the median, ulnar, peroneal, and posterior tibial nerves as well as meas urement of the conduction velocity of the slower fibers in the ulnar nerves. The sen sory thresholds were measured with the use of square wave pulses of 1 msec dura tion. A detailed description of these methods and our criteria for normal and abnormal, based upon measurements on ment was insignificant considering one stockkeeper (out of seven), and one 120 healthy persons, have been published the short exposure time and the female paper cutter (out of 20). Thus, the earlier." results of the measurements made (Table 2). Nor could mineral oil vapor be a hazard because of its low vapor pressure (1.8 mm Hg at 100 C) and high boiling point (297 C). total number ofexamined workers was 33, one of whom was a woman. The workers were first examined clini cally and had a number of laboratory tests taken (blood cell count and measurements of thrombocytes, serum transaminases, The hospitalized patients received other examinations, including thin-needlc liver biopsy, and in some instances lumbar puncture, pneumoencephalography, clini cal neurological and otoneurological ex aminations, and psychological testing.3 urinary protein, and glucose). On the basis The most relevant methods of examina Determination of Diphenyl in Air of anamnestic data, clinical findings, or pathological laboratory tost results, eight tion are referred to in connection with the case reports. Diphenyl in the air was determined men were admitted to the hospital for clos both by direct ultraviolet light ab sorption spectrophotometry and by er examination (see case histories), and 14 other men had a neurophysiological exam Results II spectrofluorometry. The air samples ination. Since the hospitalized men also Summary of Clinical Find I were collected in ethyl alcohol (two were examined by these methods, 22 sub ings.--The most common complaints I 1 I flasks in series). The UV-absorption was measured at 248 nm. The sam ples were excited at wavelength 258 jects in all were examined ncurophysiologically. The electroencephalogram was recorded for 30 minutes and included a three-min were headache, gastrointestinal symptoms (diffuse pain, nausea, indi gestion), polyneuritic symptoms i nm by spectrofluorometry and the ute photostimulation and a three-minute (numbness and aching of the limbs), emission was measured at 314 nm. hyperventilation. The electroneuromyo- and general fatigue. These symptoms j The methods will be published in de graphic (ENMG) examinations com were so common that diphenyl must tail elsewhere.1 prised electromyography (EMG) of five to be blamed for most of them even tI i Arch Environ Health/Vol 26. Feb 1973 Diphenyl Poisoning/Hakkinen et at 71 r DSW 345768 i STLCOPCB4084268 Table 3.--Liver Function Tests of Eight Men Hospitalized for Suspected Diphenyl Poisoning Case Ago Exposure esr No. Grrt Time <yr) Liver Biopsy Retention, %* SGDTt 2 27 8 Normal 4 20 3 52 12 Incipient 17 100 hepatic cirrhosis 4 27 5 55 6 43 7 44 6 Normal 16 Normal 13 Fatty metamorphosis 16 Normal 3 2 17 8 50 24 ' 20 20 8 30 9 55 5 Normal IS Fatty metamorphosis 10 54 54 Forty-five minutes. tVVrofc/evsky-units. SGPTt 28 120 61 27 32 25 59 64 though no control group was used for comparison. The distribution of the main symptoms was as follows: head ache, 13 cases; gastrointestinal symp toms, 13; polyneuritic symptoms, 12; fatigue, 11; giddiness, 7; and symp tom-free, 7. The objective symptoms are men tioned in connection with the case reports. The laboratory tests yielded little information; however, of the 33 subjects studied, ten had elevated (more than 40 Wroblevsky [WR] units) serum glutamic oxaioacetic transaminase (SGOT) or serum glu tamic pyruvic transaminase (SGPT) levels, or both. Of the 22 men examined neuro physiologically, only three were with out pathological findings. Four had borderline findings and the remaining 15 had one or more pathological test results. The distribution of neuro physiological findings was as follows: abnormal findings in EEG, three cases; abnormal findings in ENMG, five; abnormal findings in EEG and ENMG, seven; borderline findings, four; and no abnormal findings, three. The frequency of specified neuro physiological findings in the 22 men exposed to diphenyl was the follow ing: Of eight EEG abnormalities, there were six diffuse slow wave ab normalities and two spike and wave discharges (3 to 6 cycles per second). There were eight abnormal alpha dis tributions, four with other pathologi cal findings and four without. There were nine instances of reduced nerve conduction velocity, three with MCV slowed and eight with slower fibers affected. Nine pathological EMG find ings included three with reduced number of motor units and six with reduced number of motor units plus fibrillations. Elevated sensory threshold was found in five instances. According to these results, diphen yl seems to exert a toxic action both on the brain and on the peripheral nervous system. The frequency of pathological findings was remarkably high even considering that the sub jects were selected. A more detailed consideration of the neurophysiolog ical findings will be published else where. Liver biopsy was performed on all hospitalized subjects. The results of this examination together with other indicators of liver function are shown in Table 3. In five cases indications of liver injury were present. The biopsy showed hepatic cellular changes in three of them. These findings, togeth er with the autopsy findings of case 1 (see below), suggest that the liver is one target for the toxic effects of di phenyl. Report of Cases - Because there are no data published on human diphenyl poisoning, the nine cases studied more thoroughly will be presented in some detail. The first case is the fatality that initiated the survey: since very little of the toxicology of diphenyl was known to us at this stage, some relevant examina tions were not made. Case 1.--The patient was a 32-year-old man, exposed for 11 years as an oil-man (see Table 1), who became ill in the sum mer of 1969. He had been completely healthy until then, did not use any drugs, and consumed alcohol moderately (about 500 gm expressed as absolute alcohol per month). His first symptoms were fatigue, abdominal pain, headache, and psychic disturbances (irritability, sleep disturb ances, loss of memory). He visited two physicians during the fall, but no diagno sis was made. In November he had to stop working and was admitted to the hospital four days later. He was somnolent, icteric, and had severe ascites and massive edema in the legs (6.8 and 3.7 liters of ascites, respectively, were tapped on two occa sions). Laboratory values included the fol lowing: hemoglobin, 11 gm/100 ml; leuko cytes, normal; thrombocytes, 118.000/cu mm; urine protein, positive; plasma creati nine, normal; SGOT, 128, ISO, and 94 Wr units; SGPT, 45, 100, and 116 Wr units; and total bilirubin, 17.3 mg/liter, of which 0.3 mg/liter was directly reacting. The prothrombin index (Quick) was first 24% and later 5%. The value for total serum protein was 60 gm/liter (30.3% albumin, 4% ayglobulins, 3.4% a.-globulins, 62.3% /3- plus y-globulins). The IgG and IgA were increased and the complement decreased. Sternal biopsy suggested hemolytic ane mia. The EEG showed diffuse theta and delta activity compatible with brain damage. The patient was treated with predniso lone (50 r.ig/day), parenteral mcnadicnc and thioctic acid (Thioctan), and neomycin (to prevent liver coma). In spite of all ef forts, his condition grew progressively worse. On Dec 17, 1969, he had a large hematemesis. Two days later he died. At autopsy, -which was performed on the 11th day after death, the liver showed ne crosis of most cells. The findings were partly compatible with acute yellow necro sis, but there were also cirrhotic areas. The kidneys showed severe nephrotic changes, and the heart muscle, degenera tive changes. The brain was edematous and there was degeneration of the gan glion cells of the gray substance. The bone marrow- was hyperactive, showing in creased numbers of immature white and red blood cell precursors. There were only a few megacariocytes. The patient was conscious until the last few days. During the four weeks in the hospital, his history was thoroughly inves tigated. There was no history of any liver disease or of severe infections. Alcohol seemed to be an unlikely cause for severe liver injury in such a young man. The fact that the patient had been working regu larly until four days prior to hospitaliza tion also spoke against alcoholism. He firmly denied any abuse, admitting only one bottle of vodka (500 ml) per week or 72 Arch Environ Health/Vol 26, Feb 1973 DSW 345769 Diphenyl Poisoning/Makkinen et al STLCOPCB4084269 t even less. The fact that he had been using tetrachloroethylene for washing the ma chines was given thorough attention; however, it seems unlikely that such a small exposure (about 10 to 75 ppm for one hour, five to ten times a year! could con tribute to the fatal poisoning. He also firmly denied any abuse of this agent. Since no other plausible cause could be found, and since there were pathological changes in many different organs, the proof in favor of poisoning seems convinc ing. The most likely agent was diphenyl; this hypothesis was further supported by the long exposure to concentrations occa sionally reaching even more than a hundred times the threshold limit value (TLV). Case 2.--A 27-year-old man had been exposed to diphenyl for ten years at the paper machine and as an oil-man. He complained of headache, weakness of the left arm, and abdominal pain. Liver func tions were normal. The clinical neurologi-' cal examination revealed motor dysfunc tion of the left hand and loss of superficial sensation in the areas of the ulnar nerve. The EEC and ENMG findings were normal. Case 3.--A 52-year-old man had been exposed for 12 years as a loader and a di phenyl stockkeeper. Skin absorption must '' have been considerable since he had been handling diphenyl with his bare hands. His alcohol consumption was about one bottle of wine a week. His main com plaints were fatigue, abdominal pain, diarrhea, sweating, dysuria, impotence, and numbness of the legs. The transami nase levels were elevated (SCOT, 100 and SGPT, 120 Wr units), the sulfobromophthalein (Bromsulphalein, BSP) reten tion was 17% (normal upper limit, 8%), and the y-globulins were increased. The liver biopsy showed parenchymal and por tal tract fibrosis. The lobular architecture had deteriorated. The changes w'ere indic ative of incipient cirrhosis. The neurologi cal examination revealed horizontal rhythmic nystagmus, hyperhidrosis, and impairment of all sensory qualities on the right side of the body. The sensory findings were compatible with a thalamic lesion. The ENMG findings were normal, and the EEC findings were borderline, showing unusual alpha distribution. Case 4.--A 27-year-old man had been working as an oil-man for six years. His health had been good, and his alcohol con sumption was "slight." During the last two to three years he had developed increasing headache, fatigue, and numbness of the limbs. His memory was subjectively weak ened, he slept badly, his potency was poor, and he was irritable. Occasionally he had diarrhea and dysuria. The only pathologi cal liver function was a transient eleva tion of the transaminase levels (SGOT, 50 and SGPT, 61 Wr units). The clinical neu rological examination revealed organic mental deterioration, hyperhidrosis, trem or. and neurogenic muscular atropy in the interosseus muscles. The cytological study of the cerebrospinal fluid revealed lipophages compatible with tissue destruction. The pneumoencephalogram was normal, however. The EEG was abnormal, show ing mild to moderate diffuse slow wave abnormalities, particularly in the left pos terior areas. The first ENMG was within normal limits. The acoustic and vestibular functions were disturbed. The psychologi cal tests showed significant deterioration, especially for psychomotor functions. The examination was repeated seven months later; in the interim there had been- no exposure to diphenyl. The condition of the patient had deteriorated. The EEG was as before, but the psychological tests were more abnormal. As a new feature, poly neuropathy was now diagnosed (slowing of nerve conduction by 20%, fibrillations, and diminished number of motor units in the EMC). Case 5. --A 55-year-old man had been working as a diphenyl-paper line operator for 16 years. His right forearm had been wounded in the war and was partially pa retic. He had had low-back pain for 18 years. In 196S he was operated upon be cause of a suspected prolapse of the presacral intervertebral disk but only an atrophic nerve root was found. During the last two years the patient had suffered from fatigue, headache, loss of memory, and pharyngeal irritation. Results of the liver tests were normal. The neurological examination showed organic mental dete rioration and spontaneous rhythmical nystagmus. The otoneurological examina tion revealed perceptive hearing loss and disturbance of the vestibular function. The EEG showed slight diffuse slow wave ab normality. Nerve conduction was slowed by about 10% both in the peroneal and posterior tibia] nerves, especially in the loft leg. Fibrillations and a diminished number of motor units were noted in the 'EMG. A peculiar spontaneous activity, occurring in rhythmical series lasting from 10 to 15 seconds, was registered from the left anterior tibial muscle. The ENMG findings were not typical for mechanical nerve root compression, but were more compatible with polyneuropathy or partly with neuronopathy of anterior horn cells. The patient was considered to be incapable of working. Although there was evidence of poisoning, his orthopedic condition ac counted for the major part ofthe disability. Case 6.--A 43-year-old man had been working as an oil-man for 14 years. He had been previously in good health and consumed no alcohol. For some years he had various symptoms ofincreasing inten sity; abdominal pain, pharyngeal irrita tion, nosebleeds, numbness of the arms, mental irritation, sleep disturbances, impotence, and loss of memory. The BSP retention was pathological vl3%; con trolled, 17%: normal upper limit, 8%). Liv er biopsy specimen showed distinct fatty metamorphosis and slight inflammatory changes. The finding was compatible with toxic changes, although nonspecific. Neu rological examination revealed organic -mental -deterioration and 6igns of motor and sensory neuropathy. Electronystag mography disclosed moderate disturbance of the vestibular function. The EEG was normal. The conduction was slowed by 10% in some peripheral nerves. The EMG showed diminished number of motor units in several muscles. Case 7. --A 44-year-old man had first worked for 2 years as an oil-man and then for 13 years as a maintenance worker. Previously, he had been in excellent health; he used no alcohol. During the whole exposure time irritation of the nasal mucosa and the conjunctivas developed during work. For several years he experi enced giddiness, fatigue, tremor, and pain in the forearms, back, and shoulders. Ab dominal pain had been oresent for three years. In addition, he complained of loss of hearing, iropotency, and mental altera tions (depressive mood, irritability, loss of initiative). There were no signs of liver injury. The clinical neurological findings included dysfunctions of the autonomous . nervous system and mixed peripheral neuropathy. There was a marked percep tive hearing loss, but normal vestibular function. The EEG showed mild diffuse slosv wave abnormalities. The conduction velocity in the slower nerve fibers was reduced by 10%. The number of motor units in the EMG was diminished. Case 8. --A 30-year-old man had been preparing the diphenyl solution for five years, two to five months a year. The rest of the time he had been working at a paper machine, situated near the oil-room, but not used for manufacturing diphenyl pa per. The diphenyl concentrations near this paper machine were not measured. As a child he had had mild hepatitis, but had made a full recovery- He used alcohol less than ten times a year. He had had head aches for several years and abdominal pain for some two years. He had lost con sciousness twice while at work. The trans aminases had been slightly increased during 1969 to 1970, but the liver was his- Arch Environ Health/Vol 26, Feb 1973 DSW 345770 Diphenyl Poisoning/Hakkinen et al 7 3 STLCOPCB4084270 rltologically normal. Objective neurological P diphenyl is completely harmless i 'dence of liver damage. The possible findings included hyperhidrosis, sponta quantities several times greater thaan neous rhythmical nystagmus, and a cen that to which workers are exposed in tral facial paresis on the right side. The EEC revealed spike and wave discharges during photostimulation, spontaneous curve normal. The conduction velocity of the slower nerve fibers was 10% less than the normal limit, but the MCVs were 1 the manufacture or use of diphenyl impregnated paper." Such a view is somewhat surprising considering the results of Deichmann et al,3 and this statement no doubt contributed to the normal. Electronystagmography disclosed 1 nonchalant handling of diphenyl in disturbed vestibular function bilaterally. \ the paper mill. itrole of alcohol can, of course, never be / eexcluded with full certainty, but the fact that all workers had had stable employment for several years, and none was known to abuse alcohol, strongly speaks against alcoholism as the cause of the liver damage found. The prognosis of the poisoning is still unknown. At present there is no A year later, the EEC showed mild diffuse ^'Although Deichmann and his' col reason to be optimistic, since some slow wave abnormality in addition to the spike and wave complexes induced by pho tostimulation. All nerve conduction veloci ties were by this time normal. Case 9. --A 53-year-old man had been working at the diphenyl paper machine for 15 years. Apart from a low-back condition he had been in good health; he used no al laborators warned of the toxicity of diphenyl as early' as 1947,3 no formal safety recommendation was given until 1968. In that year, the Ameri can Conference of Governmental Industrial Hy'gienists set a TLV of 1 mg/cu m.11 The documentation is patients' conditions seem to deteri orate in spite of complete avoidance of any contact with diphenyl. The deterioration concerns both central and peripheral nervous functions. Slight improvement has sometimes been observed, however. Thus the cohol. Subjective symptoms had been pres defective, however, since the litera final concept of the prognosis must ent for several years; headache, numbness ture contains very few observations. await the results of a longer observa of the limbs, giddiness, and abdominal Unfortunately our data, too, are diffi tion period. pain. The transaminases were slightly cult to interpret in terms of the safety increased and the BSP retention was bor derline (Table 3). The liver biopsy showed distinct centrilobular fatty metamorpho sis, characteristic for toxic substances. On EEC, there were slight diffuse slow wave abnormalities and homogenization of the ' alpha activity. The EN'.MG showed neuror` genic lesions of slight degree probably on the medullary level ranging from the cer vical to the lumbar rcgicr.. The patient was considered to be completely incapable of working. Comment This unfortunate story offers an example of how erroneous conclu of the present TLV, since exposure was much in excess of 1 mg/cu m. The only thing that can be stated is that high concentrations are anything but harmless to man. Such dangerous concentrations apparently can result from the production of impregnated fruit paper if hygienic measures are neglected. The clinical picture of diphenyl poisoning is characterized both by central and peripheral neurological lesions. The exact type of brain lesion remains to be defined. Partial demye- lination may be the most probable explanation for the peripheral find References 1. Rajzman A: Les residus de biphenyle dans les agrumes. i2csfc/ue/2ei;6:2-66, 19C5. 2. Hygienic guide series: Diphenyl. Am Ind Hyg Assoc J25:522-523, 1964. 3. Deichmann WB, et al: Observations on the effects of diphenyl, o- and p-aminodiphenyl, oand p-r.itrod:phcr.y! and dihydroxyoctauhlorodipLcnyl Upon ..Apeiiiiitrnitii aUJXiiUja. A J ITUl Hyg Toxicol 29:1-3. 1947. 4. Booth AN. et al: Reversible nephrotoxic effects of diphenyl. Toxicol Appl Pharmacol 3: 560-567. 1961. 5. Weil E. Kusterer L, Brogard M-H: Intoler ance a un produit d'impregnation anlifongique des emballages d'agrumes. Arch Mai Prof 26: 405-408.1965. 6. Weeks JL. Lentle BC: Health consider ations in the use of organic reactor coolants. J sions regarding the toxicity of an industrial chemical may lead to a false feeling of safety. Hygienic pre cautions had been inadequate and resulted in extremely high concentra ings, but this suggestion is still hypo thetical. However, even these incom plete data clearly show that diphenyl is a neurotoxic agent. It is unfortu nate that the nervous system has re Occup Med 12:246-252, 1970. 7. Siltanen E, et al: Determination of diphen yl in air. Work-Environ Health, to be published. 8. Seppnlriinen AM. Hernbcrg S: Sensitive technique for detecting subclinical lead neuropa thy. Br J Ind Med 29:443-449, 1972. 9. Hannincn H: Psychological picture of man tions of diphenyl in the air. It is clear that with such careless handling, any chemical may be dangerous. Ho ceived so little attention in animal experiments.3'4 More careful observa tions might have provided important ifest and latent carbon disulphide poisoning. Br J Ind Med 2S:374-381, 1971. Manufac ture of Diphenyl Impregnated Wrappers. Cartons ^%ver, a heavy responsibility falls on the producers, who as late as 1965 in their technical service bulletiif stated that, "Laboratory and practi cal investigations have shown that clues as to the mechanism of nervous damage. Another main target of toxic action appears to be the liver. Of the nine patients examined more thoroughly, four had histological evi- and Liners, technical service bulletin 2. London, 1957, revised 1965. 11. Threshold limit values of airborne con taminants and physical agents with intended changes. Adopted by American Conference of Governmental Industrial HvgienisLs, St. Louis, 1968. * 74 Arch Environ Health/Vol 26. Feb 1973 DSVJ 3457^1 Diphenyl Poisoning/Hakkinen et al STLCOPCB4084271