Document 2qZrk0G5Xr1w9e9880GqerVaa

re H h~ g - fi+% ^ r w ju tX ^ . C ~ 7 t * + s Tk^9D P P y E n vironm ental H ealth I'crip ectivn !vnX * ... - - ru U r *% ^^ Epidemiologic Study on Yusho, a Poisoning ^^ jL I^ * 'J p Caused by Ingestion of Rice Oil *% Contaminated with a Commercial Brand o f -, -- K. Polychlorinated Biphenyls* by Masanori Kuratsune, Takesumi Yoshimura, Junichi Matsuzaka, and Atsuko Yamaguchi In October, 1968, an epidemic of a peculiar skin disease similar to chloracne was reported in Fukuoka-Ken (Fukuoka prefecture), Japan. The epidemic was later proved to have spread not only over Fukuoka-Ken but also over 20 other prefectures in the western part of Japan (Fig. 1). It produced l,057_patients according to the latest tabulation (August, 1971) by the Ministry of Welfare. Soon after the epidemic was announced, a study group was organized by the staff of the faculties of medicine, pharmaceutical sciences, agriculture, and engineering of the Kyushu University and by the staff of the local health departments, to clarify the cause of the epidemic and to effectuate its control (1). We participated in the study group and conducted, as members of its epidemiologic study subgroup, an extensive epidemiologic investigation following the basic methodology of epidemiology (2). Fortunately, the cause of the epidemic was soon demonstrated to be the ingestion of a brand of rice oil contami nated with a commercial brand of polychlori nated biphenyls, and the disease was called "Yusho", namely oil disease. Although our observations and experiences are confined to the Yusho patients seen in F ukuokaIven, wc believe thut reporting of them will help many people in the world who arc deeply con- | , * Prepared by Department of Public Health, Faculty of Mc'Ikihc, Kyushu V unenity, Fukuoka, Japnu. cerncd about the chronic deleterious effects cf PCBs. The outline of our findings will, therefore, be presented, referring in addition to some othheerrl important observations reported by the clinical S t i ? ?and chemical study subgroups of the Yusho study group and to those collected from other sources, J Clinical Sym ptom s The most cominou initial symptoms experi- April 1972 r 119 NPC00026451 753788 Table 1. Initial ytnptema Goto e t al. Initial symptoms Patienta No. J Swelling of upper eyelids, inrreafiod eye discharge Acne-fomi eruption, follicular accentuation Edematous swelling of limbs Languisbinent Disturbances in digestive canal Numbness and other neurological signs Pigmentation of skin Total 52 38.3 46 33.1 9 e.o 4 2.9 4 2.9 9 0.6 13 9.6 130 100.0 eaced by 136 patients with Yusho were increased eye discharge and swelling of upper eyelids (38.3%), followed by acne-form eruption and follicular accentuation (33.1%), and pigmenta tion of the skin (9.6%) (3) (Table 1). With others which appeared later, the subjective symptoms of Yusho as stated by 189 patients diagnosed up to October 31, 1963, are summarised in Tabic 2. Dark brown pigmentation of nails and skin, follicular accentuation, acne-form eruption, in creased eye discharge, increased sweating a t palms, and feeling of weakness were the most notable symptoms (2). Descriptive Epidemiologic Studies First, 325 patients seen in Fukuoka-Ken from October, 1963, to January, 1969, were analyzed in order to know their distribution characteristics. One of the most im portant characteristics readily noted was a distinct familiar aggregation. Tim 325 patients belonged to 112 families. As shown in Fig. 2 and Table 3,99 percent of these patients were affected during 1968, while the remaining stated th at they became ill in December, 1967. Fifty-five percent of the patients were concen trated in the 3 months from June to August, and no significant difference was noted between sexes in monthly distribution (Table 3). For geographi cal distribution of the patients, crude incidence rates .of Yusho were calculated for 3 large cities and for tlte jurisdictional areas of the 22 local health departments of Fukuoka-Ken. Excepting 10 health departments where no canes of Yusho were reported i llic rates varied rontitlrribly from 1.0 to 58.9 per 100,000. Kx.imirmtinsi of mh'1* geographical distribution failed to intlir.ilc any common socioeconomic or environmenln! factnr which might be associated with the diVei-c. Tin* 325 patients consisted of I5S malm and 16? females, indicating that both sexes were rqiijitly affected. More than 90 percent of thrm w n r younger than 50 years (Tabic -1). Age- anti *rxspecific incidence rates again indiratrd no *iknificant sex difference but lower rik fur l*nth males and females in the age group over 0*) va n (Table 5). A nalytical Epidemiologic Studie When our study started, a comm^rrml brand of rice oil produced by K company UldurvialM as K rice oil) in Kitakyushu-Shi iKi'.aVymhu city), Fukuoka-Ken, had vaguely W n u*|rr|r.i 03 a possible cause of the disease, Ijeom* nw*t patients with Yusho seemed to have u*d n T able 2. Percent d istrib u tio n n f >m jtitmt t t i Yuiku reported by 169 patient n a n itn e l before O* i><Uf 1), t96ff. Symptoms M ain I'w w le Dark brown pigmentation of nails Distinctive hair follicles Increased sweating at palms AenelDto dun eruptions Red plaques on limbs Itching Pigmentation of skin Swelling of limbs Stiffened soles in feet sod palms of hands Pigmented mucous membrane Increased eye discharge Hyperemia of conjunctiva Transient visual disturbance Jaundice Swelling of upper eyelids Feeling of weakness Numbness in limbs Fever Hearing difficulties Spasm of limbs Headache Vomiting Diarrhea -S3 1 111 0 a a K? 91 2 4*7: 3 WJ 34 ; M3 Ma TO a :A 3 II 3 71 1 \ 4 33 o HI la (1 TV MS l a rt i 73 > 0 .VI O U If 0 3 n o U* Q *r uo N0 MO 11 4 M.O -S o 0 1 1 * # ir 120 Environmental llr-ltli IVtvf-V*"* NPC00026452 753789 F igcrc 2. Distribution of patients by sex and month ben symptoms appealed. Therefore, a thorough investigation was under taken to determine whether the patients had actually taken such special brand of oil before being affected. This was achieved by examining lot numbers appearing on the remaining con tainers of the oil used by some of the patients, shipping records of K company, and purchase and sale records a t wholesale oil dealers' offices and a t retail stores. I t was soon disclosed th at all the patients had used Iv rice oil, either canned (16.5 kg) or bottled (L.G5 kg). Furthermore, an astonishing fact became evident: No m atter where they lived, 166 or 170 patients who used only the canned K rice oil had used a very specific oil, produced or shipped by the company on February 5 and 6, I96S (Table 6). For those who used bottled K rice oil, date of production or shipment could not be confirmed, because they had no old bottles a t home. Examination of all available records concerning shipping, sale, and purchase a t K company, wholesale dealers and retail stores, however, clearly indicated a pos sibility th at 143 of 155 patients who used bottled K rice oil only had used a very specific rice oil produced or shipped from February 5 to 15, 1968. This was because such oil had been shipped to and had reached the retail stores from which they had purchased their oil (Table 6). Thus, nearly all of the patients had had a very peculiar common experience of use or possible use of a rice oil produced or shipped b y one company in a specific period of time. An attack rate as high as 63.9 percent was noted for those who con sumed the specific canned o9. In an additional survey, we examined whether those who regularly used K rice oil, but did not use the specific K rice oil produced or shipped Table 3. D istribution of patient w ith yusho diagnosed by j i n u n y 20,1969, by sex and m onth when sym ptom s appeared. Meoth Males Number Percent Females Number Percent Total Number Percent Before 1968 1968 January February March April May June July August epicenter October November December 2 1.8 0 0.0 4 2.5 8 5.1 15 0.5 18 11.4 33 14.8 27 17.1 34 21.5 17 10.8 8 5.1 1 0.6 1 0.6 2 1.2 4 l.T 0 0.0 0 0.0 6 3.6 10 3.1 12 7 .2 20 6.2 10 6 .0 25 7.7 15 8 .0 33 10.2 33 IS .8 56 17.2 32 IB.2 50 18.1 30 ie.0 ' 64 10.7 12 7.2 20 8.0 14 B.4 22 6.8 1 0.6 2 0.6 0 0.0 1 0.3 Total 158 100.0 167 100.0 325 100.0 A pril 1972 121 3 ,,PC 00026453 753790 Table 4. Distribution of 325 patient* w ith yusho diagnosed by January 20,1959, by aex and age group. Age croup (yean) Males Number Percent Females Number Percent Total Number Percent 0-9 10-10 20-29 30-39 40-19 50-39 0-69 70-79 Total 37 23.4 38 24.1 28 17.7 30 1S.0 11 7.0 9 5.7 4 2.5 1 0.5 168 100.0 27 18.2 28 16.8 88 21.6 39 23.4 23 13.8 11 6.6 3 1.8 0 0.0 187 100.0 64 19.7 6G 20.3 61 16.7 69 21.2 34 10.5 20 6.2 7 2.2 1 0.3 325 100.0 in the period in question, were free of the disease or not. A group of 113 persons of 29 households living in an apartm ent house had purchased canned K rice oil as a unit from one dealer and divided it among themselves fairly regularly from December, 1907, to September, 1903, except for the period from January to April, 1908, when no bulk purchases were made. Their disease experience in 1903 was carefully explored through investigation of their medical records a t hospitals and doctors* offices. No case of Yusho was found among them. All these results suggested th a t Yusho was caused by use of the K rice oil th a t was produced o r shipped from K company on February 5 and 6, 1968, or soon thereafter. Nevertheless, some other factors or agents might have been the primary or secondary cause of the epidemic. Therefore two case-control studies were done. In one, the per- sonai backgrounds of the patients and matched controls were compared. In the other, the use of oil and fats in the households of the patients and the controls were compared. .121 patients and their 121 healthy controls, (53 males and 68 females) matched by age, sex, and place of residence to each of the patients, were selected and asked 60 questions concerning their occupations, medical background, general health status, habits, customs, diet, pets, and other characteristics of their lives. As 6hown ir Table 7, only one of the 60 personal factor examined, namely habit of "eating fried food or tempura nearly every day**, was significanti; more commonly seen among the patients tha among the controls. In the latter case-control study, 69 householc with Yusho patients were matched by place i residence w ith 207 control households withoi Tabi S. Age-specific incidence rates for Y usho, by c ia f portent. Age croup (yean) Incidence rates per 100,000 Males Females 0-9 10-19 20-29 30-39 40-19 50-59 60-69 70 and over Total 11.4 8.6 8.9 6.6 9.1 10.3 9.6 11.9 5.4 9.3 5.4 7.2 3.5 2.4 1.7 0.0 8.3 8.1 Table 6. Rice oil used by Y usho p atien ts. - No. patients Specifications of oil used Type D ate of production or shipm 166 (51.1) Canned February 5 and 6,1968 4 (1.2) Canned Unknown 143 (44.0) Bottled 13 (3.7) Bottled Unknown, but use of oil ship from February 5 to 1 5 ,1W is very probable, Unknown 325 (100 122 E n v iro n m e n ta l H e a lth P e r tp e f NPC00026454 753791 41 Table 7. Results of case-control study. Items investigated Cases Controls %% Allergic to fish Allergic to aspirin Allergic to other drugs Having hath facilities at home Taking bath everyday Having peU a t home Living in bouse smaller than 66 m1 floor space 6.0 0.0 7 .fi 84.7 73-0 18.3* 60.9 7.5 4.2 6.6 85.5 70.6 36.5* 66.1 Handling agricultural chemicals Taking cod liver oil Talcing vitamin pills Taking other restorative drugs Water supply available at home 2.5 10.8 23.2 9.1 81.3 6.6 8.3 18.3 7.5 74.7 Diniag out occasionally Dining the same meals with families Eat green vegetables daily Drink milk nearly everyday Take butter nearly everyday Eat eggs nearly everyday Eat fried foods or tempura nearly everyday Eat foods prepared with oil nearly everyday Eat fish nearly everyday Take mayonnaise nearly everyday Eat instant "rahmtn" or Chinese noodle nearly everyday 28.1 88.8 63.1 49.0 22.4 61.7 22.4* 21.6 21.6 10.8 10.8 30.6 89.6 58.9 39.0 24.9 59.8 11.6* 29.1 29.1 10.8 10.0 p<0.05. such patients. A distinct difference was noted between the two groups only for regular use of rice-bran oil, namely 96 percent of the patients' households affirmed it while only 31 percent of tlic control households did (Table 8). Thus, the case-control studies clearly indicated th a t none of the factors tested except use "of K rice oil could account for the disease. Dose-Response Relationship To prove a causal relationship, a definite doseresponse relationship is needed. A rough estimate of the quantity of the specific IC rice oil consumed by tttfh patient and his family members was made disregarding their age, sex, amount of food intake, and possible lass of oil during and after cooking (4). Eighty of the 14G users of the specific canned K rice oil in question were believed to have con- , sunned, individually, less than 720 ml. F or these / f SO light users, the attack rate of Yusho was 83 percent, while for those who were estim ated to have used more than 720 ml, it was 100 percent (Table 9). I t was also demonstrated th at the'tar'* proportion of severe cases of Yusho clearly in- ^ creased with the amount of oil consumed. While the clinical severity of the disease was not found to differ significantly between the sexes, it did differ considerably according to age, as shown in Table 10 and Fig. 3. The proportion of severe cases among those aged 13 to 29 was significantly larger than th a t of other age-classes. Therefore, each of the three groups of users, with different levels of oil intake, was standardized for age using the age composition of the whole MG users as standard. The figures, however, hardly changed from those shown in Table 9. Thus, a d ea r doseresponse relationship could be demonstrated, even though the estimates of the dose were inac curate (4). Toxic Agent In view of all these epidemiologic observations, we concluded th at the K rice oil of specific pro duction or shipments hod caused Yusho. Now, why was the oil toxic? The chemical stu d y sub group (chief: Prof. H . Tsukamoto, Faculty of Pharmaceutical Sciences, Kyushu University) demonstrated that the canned K rice oQ produced or shipped on February 5, 1968, and used by some of the patients contained about 2,000 to Table 8. Result* of case-control stu d/ on olio used. F at or oil Cases No. of % households Controls No. of % households Butter Margarine Sesame oA Rape-seed oil Rice-bran oil Lord Other oils 35 fi0.7 44 63.8 21 .3 0 .5 10 14.5 66 95-7 12 17.4 13 16.8 105 50.7 127 ' 61.4 85 41.1 77 37.2 64 30.9 38 18.4 117 50.5 Cases: 09 patient households. Controls; 207 non-patient households. A pril 1972 123 R PC 00026455 Tab) 9. Itclalton betw ren llie am o u n t of ib e K rice oil u*cd by p atien ts an d tb e lr clinical severity, Amount of oil Kon-cffccted No. % Light cases No. % Severe coses No. % Total No. % Less than 72(1 ml 720-1,440 ml Mone than 1,440 ml 10 0 0 (12.0) (0.0) (0.0) 39 (49.0) 14 (31.0) 3 (M.O) 31 (39.0) 31 (69.0) 18 (S.0) 80 (100.0) 43 (100.0) 21 (100.0) 3,000 ppm of Kanochlor 400, (Kanegafuchi Chemical Industrial Co. Ltd.) a brand of poly chlorinated biphenyls (chlorine content: 48%) (5). In this discovery, Prof. K. Ioagami of the De partment of Food Technology, Faculty of Agri culture, K jnshu University, and bis associates made most admirable contributions as members of the chemical study subgroup. The study subgroup also demonstrated th at the oil was not contaminated with toxic agents such as Cu, Ni, Zn, Co, As, Hg and Pentachlorophenol. Further more, it found th at most of the components of Kanechlor 400, particularly those corresponding to the peaks of higher retention times in the gas chromatograms, were retained in the sebum, subcutaneous fat, mesenterium, mesenteriolum, extrapenton cal adipose tissue, appendix ver miformi, heart, sternal marrow, small intestine, trachea, and other organs of patients, and can be transported into the fetus through the pla centa (5,6,7). To examine whether only the K rice oil produced or shipped in the period in question was contaminated with Kanechlor, the chemical study subgroup analyzed 109 samples of the bottled rice oil which had been shipped between October, 1967, and October, 19G8. Gas chromatographic analysis revealed that a significant contamination of the bottled oil was limited only to those produced or shipped between February 7 to 1 0 ,196S (5). No analysis could be made of the bottled K rice oil produced or shipped on February 5 and 6 because of the lack of samples. Similarly, 479 random samples of bottled K rice oil were analyzed for chlorine content by the X -ray fluorescence method with a count meter. Again, only the samples of February 7 to 10 contained & large am ount of chlorine (maximum 462 ppm). None of the oils shipped in other months were contaminated with more than a trace amount of chlorine. Thus, the results of chemical studies completely coincided with those achieved by epidemiologic approaches. By the way, the Kanechlor had been used at the K Company in the equipment for heating the proc essed oil a t a reduced pressure in order to remove the odorous m atters of the rice o (Fig. 4). I t is Table 10. Q ln lcal verity by age. Amount of o used (ml) Noo-offacted Number of patients by clinical grade Light* Severa* Total <720 720-1440 0-12 13-29 30Total 0-12 13-20 30Total 3 (16.7) 2 (8.3) 5 (13.1) 10 (12.5) 0 (0) 0 (0) 0 (0) 0 (0) 13 (72.2) 7 (29.2) 10 (50.0) 39 (48.8) 5 (30.0) 1 (0.7) 8 (40.0) 14 (31.2) 2 (11.1) 15 (62.5) 14 (36.9) 31 (38.7) 5 (50.0) 14 (93.3) 12 (60.0) 31 (68.6) 18 (100.0) 24 (ICO.O) 38 (100.0) 80 (100.0) 10 (100.0) 15 (100.0) 20 (100.0) 45 (100.0) * "Light'*correspond!) to gredes I and II while "severo'* to grades III nod IV used bx.Goto e t al. 124 E n v iro n WUUIM &VlDJieCttVCS NPC00026456 753793 hyperkeratosis and atrophy of epidermis and cystic dilatation of hair follicle, especially a t the f head. A marked increase of melanin pigme;nts in p the basal cells of epidermis was also noted (9). Since no such symptoms a t birth or stillbirth has been experienced in Japan during the period in which their incidence among the patients was extremely high, and also since none of the mothers had had any unusual experiences, for instance, in '1 &use of drugs or in health status, these unusual phenomena could be considered to have been caused by ingestion of the contaminated o il^ However, a clear dose-response relationship bo--% tween the oil consumption and such phenomena L Figcbe 3. Fercentsge of severe cases of Ytubo by sge. could not be shown because of the limited number l of eases. The Amount of the contaminated o i l ' believed th at it must have leaked from the consumed during pregnancy ranged from 0.3 to 3 heating pipe and contaminated the oil, because nail openings were discovered in the old pipe. Rice eran A m ount o f K anechlor 400 Io g e ste d by Patients Borioso hith fttcxNE One hundred forty-six patients who w e proved to have used the contaminated canned Defatted bran Du e o il K rice oil of February 2 and 6 by our investiga tion were used for the estimation of the amount of After k?wal of sxven. Kenechlor 100 ingested. As stated, the approxi TREATED KITH 500IIH fETAFHOSPMTE. mate amount of the oil consumed could be calcu lated for each of the patients. I t was on average about 500 mL Since the concentration of AM) CENTRIFUGED ________ L i Oil Kanechlor 400 in the oil was 2,000 to 3,000 ppm, the average amount of Kanechlor 400 ingested Treated J th KiSH - by a patient was estimated to be about 2 g (4). Similarly, tbe minimum dose of K&necbTor 400 consumed by a patient was estimated to be about MH LAYER n Oi l 0.5 g. Neutrali(zed with KjSCn S a s s i w ith water Babies Born to P atients dnd N on-affected AM) FILTERED Wives of P a tie n ts "Dark oil* Thirteen women consisting of 11 with Yusho and 2 unaffected wires of patients were shown to i have delivered 10 live bom and two stillborn Qu a removed w ith MUTE PORCELAIN CLAY babies from February 15 to December 31, 1968 :S, 10,11). As shown in Table 11, nine of them had unusually grayish, dark-brown stained skin and similar pigmentation of the gingiva and walk Deodorized bv bating AT WER 200 C AT 3 TO t| te was noted in 5ve of them. Increased eye discharge was also notable in most of them. Histological Final products examination of a stillborn fetus showed a marked Figorc 4. Flow sheet of rice oil production. A pril 1972 125 S UPC00026457 753794 Tattle 11. Babtea bnrn to patients and unaffected v Itcs of patient* and their ,u*e of K rice all. Amount af oil Pregnancy Grade of Sex Small* Mother Age ured period clinical Delivery of for* Stained Stained Stained No. during when oil severity baby date akin gingiva nail pregnancy used of mother* (M Increased eve Neonatal discharge jaundice 1 28 0.3 3rd 2 Normal M No trimester 2 24 T 1 3 Normal F No 3 22 1.4 Later hall Normal Foreep M No of 2nd trimester 4 27 0.7 2nd 1 Normal M Yes trimester 6 26 0.7 l i t 3 Normal F No trimester 6 20 1.4 Later half 3 Normal M No of 2nd trimester 7 30 1.1 Whole 1 Normal M Yes 8 23 7 Whole 3 Normal M 30 0 33 7 7 T M Yes section 10 29 0.3 Early half Normal Normal F No of 2nd trimester I t 28 7 7 2 Normal M No 12 33 2.6 Early half 4 Stillbirth 7 T of 2nd trimester 13 25 7 7 3 Stillbirth F Yes 7 + + + + + + + T + + + " ---- + ++ + ---- ---- ++ '+ + Tt T7 * + + + + + + + + + + + ++ a -L. + + + + Table 12. Prognosis o f p atien ts w ith Yuaho.* Grade of clinical Clinical conditions It t1!1 severity** Improved Stations! Worsened Total iiI,. 0 18 (00.7) (25.0) 2 (8.3) 21 (100.0) i- 1 30 (51.7) 18 (27.6) 12 (20.7) 3S (100.0) s a 23 (52.3) 16 (38.4) (11.4) 44 (100.0) i. 3 4 Total 12 (52.2) 0 (0) 81 (50.0) 10 (43.5) ' 10 (100.0) 58 (38.5) 1 (4.3) 0 (0) 20 (12.8) 23 (100.0) 10 (100.0) 150 (100.0) * Calculated from the figures reported by Toshitani and Kitamura. **0: Physical complainU without akin-lesions. 1: Pigmentation of the akin and the mucous membrane. 2: Comedo formation. 3: Acnclurm eruptions. 4: Extensive distribution of ocnefonn eruptions. 126 E n v iro n m en tal H e a lth Perspceti U PC 00026458 753795 *' - - - ' ' T'1 V* *. l| 2.6 liters (Table 11) (S). Twelve of 13 fetuses were smaller than the national standards, and 4 of them were smalMor-dates babies (S,10). As they grew older, the stain in their skin gradually faded (11). Xo evidence has so far been obtained with regard to any physical and mental retarda tion of the babies, but we suggest th at s par ticularly careful and prolonged follow-up observa tion should be maintained for their future (S). Growth o f Affected Children To examine whether Yusho disturbs children's growth, the affected school children, 23 boys and 19 girls, were compared in 1967, 1968, and 1969 with their 719 healthy classmates matched by sex. The gains of the affected boys in both height and weight decreased significantly after the poisoning, while the affected girls showed no definite change in this respect (12). Current State of Patients More than 3 years have passed since the epidemic was reported. I t is a heart-breaking fact that many patients with Yusho are still tortured by the sickness because no curative treatments have been discovered yet. In summer of 1970, a moss clinical examination of the Yusho patients was carried out in Fukuoka-Ken, and the clinical state of the patients examined were compared with their previous findings observed in summer of 1969. As shown in Table 12, about a half of the ln9 patients, for whom the comparison was feasible, were shown to have clinically improved signs, while the remaining half showed no such favorable signs, and more than 10 percent of the patients were even worsening (13). I t should be noted, furthermore, th at even many of those who appeared to be clinically improving had several serious complaints, such as persistent headache, general fatigue and feeling of weakness, numbness in limbs, weight lma, and others (14). All these facts clearly indicate that recovery from Yusho is extremely difficult. To cure them as quickly os possible and to prevent another epidemic of Yusho, all possible world-wide cooperative efforts arc highly desired. (ram the middle of February to the end of March, 196S, an epizootic of a strange disease closely resembling chick edema disease occurred involving mare than two million chickens in the western part of Japan (1 5 ,IS). More than 400,000 chickens were reported to have died. The disease was characterized by such clinical signs as labored breathing, droopiness, ruffled feathers, high mortality and decreased egg production (15,18). Autopsy revealed a marked subcu taneous edema, hydropericardium, ascites, and pulmonary cdoma, muscular ecchymosis in the thorax or inside of the thigh, and yellowish mottled appearance of the liver (15,17,18). An epizootiological investigation demonstrated th at the disease was caused by feeding chickens with specific lots of commercial brands of formula chicken feeds manufactured b y two companies. In view of the fact th a t the K rice oil used by Yusho patients had been contaminated with K&nechlor 400, the toxic feeds were analyzed for chlorinated hydrocarbons and proved to contain Kaneehlor 400 (16,19,20). The experimental reproduction of the disease by administering this chemical mixture was successful (16,20,21). The reason the chicken feeds were contaminated with Kaneehlor 400 could be reasonably understood by the following facts: both of the chicken feed manufacturers had been using "D ark oil" pro duced by the K company (Fig. 3) as an ingredient of their fonnula feeds, and they had actually used "D ark oil" purchased from the company from February 6 to 27, 1968. The remaining sample of " D ark oil," used for production of the toxic formula feeds, was also shown to contain about 1,300 ppm of Kaneehlor 400 (16,20). Thus, it became clear that both the epidemic of Yusho and the epizootic of the disease among chickens had been very closely associated, being caused b y intake of the oils contaminated with K&ne chlor 400. I t is very unfortunate, however, th a t the epidemic of Yusho could not have been pre vented even though a large scale epizootic of such an unusual chicken disease had preceded the incidence of Yusho by more than 6 months. REFERENCES 1. Kabuki, S. 19G9. Foreword, Reports of the Study Croup for "Yushon (Chlorabiphenyb Poisoning), Fukuoka Acta Med. 60:400. Z Kurstnunc, M. et ml. 1609. An epidemiologie study or uYusbo" or ehloroblphenyb powoning. Ibid. 60: 513. | 3. Goto, M. ond Iliguehi, K. lOf&LThe symptomatology April 1972 127 NPC00026459 753796 ; i V i ? it?v ;V t. 'i of Yurfio (chlorolphenyls poisoning) in dermatology, Fukuoka Acta Med. GO; 403. 4. Yoshimura, T. 1071. Epidemiological analysis of "Yusho" patients with special reference to sex, age, clinical grades and oil consumption. Ibid 02:104. 5. Tfukamoto, H. et al. 19G9. Hie chemical studies on detection of toxic compounds in the rice bran oils used by the patients of Yusho, Ibid 0:406. & Kajima, T. 1071. Chlorobiplienyls in the sputa and tissues. Ibid 62:25. 7. Kijuehi, M. et al. 1071. Two autopsy cases of chronic chlorohtplrenyls poisoning. Ibid G2: S9. 8. Yamaguchi, A , Yoshimura, T. and Kuratsune, M. 1071. A survey on pregnant women having consumed rice oil contaminated with chlorobiphcnyls aod their babies. Ibid 02:117. 0. Kikucht, M. et sL 1909. An autojwy case of stillborn of chtorabiphenyls poisoning. Ibid 00: 480. IQl Taki, I., Htsanaga, S. and Amagaac, Y. 1060. Report on Yusho (chlorobiphenyls poisoning) pregnant women and their fetuses. Ibid 60:471. 11. Funatsu, I. et a l 1071. A chlorohiphenyls induced fetopathy. Ibid 62:1391 12. Yoshimura, T. 1B7L A case control study os growth of school children with Yusho. Ibid 62:109. IS. Tcshitaui, S. and Kilnmura, K. 1071, Clinical observa tion of Yusho (chlorohiphenyls poisoning), especially further atudy of its dermatological finding?. Ibid 62: 132. 14. Okumura, M., Hirayama, C. and Uxnwa. M. 1971 Study of Yusho (chlorobiplienyla poisoning) in clinical examination. Ibid G2: 123. 15. Kohanawa, M. et al. 1969. Poisoning due to an oily by-product of rice-bran similar to chick edemu di*ca?c. I. Occurrence and toxicity test. Natl. Inst. Aniai. Health Quart. 9:213. 16. Kohanawa, M. et ah 1969. Poisoning due to an oil by-product of rice-bran similar to chick edema disease. 1L Tetraehlorohiphenyl as toxic substance. Ibid 9:220. 17. Shoyn, S. et al. 1969. Pathological changes c: pmsomr.? in chickens due to dark-oil, an oily by-product of rice bran. Ibid 9:229. 18. Hogs, K. et al. 1970. Studies on the toxic principle in a certain by-product of rice oil rendering. 1. Toxicitic on the chick. Japan. J. Zootechnieal ScL 41: 336. 19. Koga, K. et al. 1970. Studies on the toxic principle ir. a certain by-product of rice oil rendering. H. A survey of a toxic suhstance. Ibid 41:439. 20. Koga, K. e t ah 1971. Studies on the toxic principle ir. a certain by-product of rice oil rendering. III. Toxicity ' of chlorinated biphenyl an chieka and summarized reaulta of I-III, Ibid 42:16. 2L Goto, K., Sakaguchi, K. and Ogawa, K. 1969. Hydropericardium assay of rice oil which caused Yusho and of Kanechlor 400 in chickens. Ibid 60:533. Environm ental H ealth Per*p e d i' NPC00026460 753797