Document bq0qZgrpZYvNDQwO4x22RYNg

Environmental Health Perspectivej Epidemiologic Study on Yusho, a Poisoning Caused by Ingestion of. Rice Oil Contaminated with a Commercial Brand of Polychlorinated Biphenyls* by Masanori Kuratsune, Takesumi Yoshimura, Junichi Matsuzaka, and Atsuko Yamaguchi ' In October, 1968, an epidemic of a peculiar skin disease similar to chloracnc 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 1,057 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). Wc participated in the study group and conducted, as members of its epidemiologic study subgroup, an extensive epidcmiologio 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 tho disease was called "Yusho", namely oil disease. Although our observations and experiences are confined to the Yusho patients seen in FukuokaKen, we behove that reporting of them will help many people in the world who arc deeply eon- earned about the chronic deleterious effects cf PCBs. The outline of our findings will, therefore, be presented, referring in addition to some other important observations reported by the clinical and chemical study subgroups of the Yusho study group and to those collected from other sources. Clinical Symptoms The most common initial symptoms experi- ^ f [ | j * Proparcd by Department of Public Health, Faculty of Mcdicino, Kyushu University, l'ukuoku, Japan. ,# i iuw.c. *. *-uwiuu. ... ...........r. ....... April 1972 119 i I- STLCOPCB4013160 *L *- f fa. '|f j". Tabic 1. Initial symptoms Goto ft nl. Initial symptoms Patients No. Vc Swelling of upper eyelids, increased eye discharge Acne-form eruption, follicular accentuation Edematous swelling of limbs Lnnguishmcnl Disturbances in digestive canal Numbness and other nourologicul signs Pigmentation of skin Total 52 38.3 45 33.1 0 . 6.6 4 2.0 4 2.0 0 G.G 13 0.0 136 100.0 were reported, the rates varied considerably from 1.0 to 58.9 per 100,000. Examination of such geographical distribution failed to indicate any common socioeconomic or environmental factor which might be associated with the disease. The 325 patients consisted of 15S males and 167 females, indicating that both sexes were equally affected. Nlorc than 90 percent of them were younger than 50 years (Table 4). Age- and sexspecific incidence rates again indicated no sig nificant sex difference but lower risks for both mules and females in the age group over GO years (Tabic 5). Analytical Epidemiologic Studies cnced by 136 patients with Yusho were increased oyo discharge and swelling of upper eyelids (38.3%), followed by acne-form eruption and When our study started, a commercial brand of rice oil produced by Iv company (abbreviated as K rice oil) in Kitakyushu-Shi (Ivitakyushu city), Fukuoka-Ivcn, had vaguely been suspected follicular accentuation (33.1%), and pigmenta as a possible cause of the disease, because most tion of the skin (9.6%) (3) (Table 1). With others patients with Yusho seemed to have used it. which appeared later, the subjective symptoms of Yusho as stated by 189 patients diagnosed up to October 31, 19C8, arc summarized in Table 2. Table 2. Percent distribution of symptoms of Yusho reported by 189 patients examined before October 31, Dark brown pigmentation of nails and skin, 19611. follicular accentuation, acne-form eruption, in creased eye discharge, increased sweating at palms, and feeling of wcukncss were the most Symptoms Males Females (N-80) (N-100) notable symptoms (2). Dark brown pigmentation of nails S3.1 75.0 Distinctive hair follicles 6-1.0 56.0 ( Descriptive Epidemiologic Studies l Incrcoscd sweating at palms 50.0 55.0 First, 325 patients seen in Fukuoka-Iven from Acnclikc skin erup'ions 87.6 82.0 October, 1968, to January, 1909, \Vcre analyzed Red plRqucs on limbs I telling 20.2 42.7 16.0 52.0 in order to know their distribution characteristics. Pigmentation of skin 75.3 72.0 One of the most important characteristics readily Swelling of limbs 20.2 41.0 noted was a distinct familiar aggregation. The Stiffened soles in feel and palm* A 325 patients belonged, to 112 families. As shown of hands Pigmented mucous membrane 24.7 56.2 29.0 47.0 { in Fig. 2 and Table 3, 99 percent of these patients were affected during 1968, while the remaining Increased eye discharge Hyperemia of conjunctiva 88.8 70.8 83.0 71.0 stated that they became ill in December, 1967. Transient visual disturbance 50.2 53.0 Fifty-five percent of the patients were concen trated in the .3 months from Juno to August, and no significant difference was noted between sexes in monthly distribution (Table 3). For geographi cal distribution of the patients, crude incidence Jaundice Swelling of upper eyelids Peeling of weakness Numbness in limbs Fever Hearing difficulties 11.2 71.0 58.4 32.0 16.0 18.0 11.0 74.0 52.0 89.0 10.0 19.0 rates of Yusho were calculated for 3 largo, cities Spasm of limbs 7.0 8.0 . and for the jurisdictional areas of the 22 local Headache \ health departments of Fukuoka-Ivcn. Excepting Vomiting Diarrhea 30.3 39.0 23.6 28.0 ' 19.1 17.0 10 health departments where no cases of Yusho } aV< X20 Environmental Health Perspectives } t DSW 029199 /' . 4'\ < ",* **'*M7T,**T STLCOPCB4013161 ; Fiuunu 2. Distribution of patients by sex and month , - when symptoms Hppeared. }}; 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 at wholesale oil dealers' offices , and at retail stores. It was soon "disclosed that all the patients had used Iv rice oil, either canned (16.5 kg) or bottled (1.65 kg). Furthermore, an astonishing fact became evident: No matter where they lived, 166 of 170 patients who used only the canned Iv rice oil had used a very specific oil, produced or shipped by the company on February 5 and 6, 196S (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 at home. Examination of all available records concerning shipping, sale, and purchase at Iv company, wholesale dealers and retail stores, however, clearly indicated a pos sibility that 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, 1068. This was because such oil had been shipped to and had rcuched (he retail stores from which they had purchased their oil (Table G). 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 by one company in a specific period of time. An attack rate ns high as 63.9 percent was noted for those who con sumed the specific canned oil. In an additional survey, we examined whether those who regularly used K rice oil, but did not use the specific Iv rice oil produced or shipped Table 3. Distribution of.paticnts with yusho diagnosed by January 20,1969, by sex nnd month when symptoms ' appeared. Month Males V Number Percent Females Number Percent Total Number Percent Before 1008 1068 January February March April May June July August . Septcmbor October November December ' Total 2 0 4 *8 . 15 IS 23 27 34 17 8 1 1 138 1.3 0.0 2.5 5.1 0.5 11.4 14.0 17.1 21.5 10.S 6.1 0.6 0.6 100.0 2 0 0 12 10 15 33 32 30 12 14 1 0 167 * 1.2 4 0.0 3.0 7.2 0.0 0.0 10.B 10.2 18.0 7.2 - 8.4 0.0 - 0.0 0 10 20 25 33 66 50 01 20 22 2 1 lOQ.O :' / ' 325 ^ 1.2 0.0 3.1 6.2 7.7 10.2 17.2 1S.1 19.7 8.9 6.8 0.6 0.3 100.o' April 1972 DSW 029200 121 STLCOPC Tabic 4. Distribution of 325 patients with yusho diagnosed by January 20, 1269, by sex and age group. Age group (years) , 0-0 ' 10-10 20-20 30-39 40-40 60-59 60-00 70-70 Totul Males Number Percent 37 3S 28' 30 n 0 4 1 158 23.4 24.1 17.7 19.0 7.0 6.7 2.5 0.5 100.0 . - Females Number Percent ' 27 10.2 28 10.8 30 21.6 30 23.4 23 - 13.8 11 C.O 3 l.E 0 0.0 167 100.0 . Total s Number 04 66 04 09 34 20 7 1 325 Percent 10.7 20.3 10.7 21.2 10.5 G.2 2.2 0.3 100.0 ' f t - . , V1 , x ' " 0. i.. > * 1, in the period in question, were free of the disease or not. A group of 113 persons of 29 households living in an apartment ltouse had purchased canned K rice oil as a unit from one dealer and divided it among themselves fairly regularly from December, 1967, to September, 19GS, except for the period from January to April, 190S, when no bulk purchases were made. Their disease experience in 19GS was carefully explored through investigation of their medical records at hospitals and doctors' offices. 7\o case of Yusho was found among them. All these results suggested, that Yusho was caused by use of the K rice oil that was produced or shipped from K company on February 5 and G, 19GS, or 60on thereafter. Nevertheless, some other factors or agents might have been tl^c primary or secondary cause of the epidemic. Therefore two ca6e-control studies were done. In ono, the per- sonal 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 G$ females) matched by age, sex, and place of residence to each of the patients, were selected and asked GO questions concerning their occupations, medical background, general health status, habits, customs, diet, pets, and other characteristics of their lives. As shown in Table 7, only one of the GO personal factors examined, namely habit of "eating fried foods or tempura nearly every day", was significantly more commonly seen among the patients than among the controls. In the latter cnv,;-control study, G9 households with Yusho patients were matched by place of residence with 207 control households without . I Tflblo 5. Age-speciGc incidcnco rates for Yusho, by sex of pulients. Table 6. lticc oil used by Yusho patients. Age group (years) Incidence rntes per 100,000 Males Fumnlca patients Specifications of oil used Type Date of production or shipment ICO fol.l) Canned February 5 and 0, 10OS It.; 0-0 11.4 S.O 4 (1.2) Canned Unknown $uA K $ 10-10 20-29 30-30 40-49 60-50 60-60 8.0 0.1 0.0 6.4 5.4 ' 3.6 6.0 10.3 n.o 0.3 7.2 2.4 143 (44.0) Bottled 12 (3.7) Bottled Unknown, but use of oil shipped from February 5 to 15, 1DGS is very probable, Unknown .'I 70 and over 1.7 0.0 Total , 8.3 8.1 325 (100.0) r.122 Environmental Health Perspectives DSW 029201 STLCOPCB4013163 1->. C 1 ri: X.1' V, 'X, v* ; V ' V' V"' Tabic 7. Results of case-control study. Items investigated Allorgic to fish Allergic ti> aspirin Allergic to other drugs Having bath facilities nt homo Taking bath everyday Having pets at home Living in house smaller thurt 00 m' floor space Cases Controls 1 %% 5.0 0.0 7.5 - 81.7 73.0 18.3* 7.5 4.2 0.0 85.5 70.0 30.6* CO.9 00.1 Mnndling agricultural chemicals Taking cod liver oil Taking vitamin pills Taking other restorative drugs Water supply available at homo 2.5 10.8 23.2 9.1 81.3 0.0 8.3 13.3 7.5 74.7 Dining out occasionally Dining the same meals with families Eat green vegetables daily Drink milk nearly everyday Take butter nearly everyday Enl eggs nearly everyday Eat fried foods or tempura nearly overydny Eat foods prepared with oil " nearly everyday Eat fish nearly everyday Take mayonnuisc nearly everyday Eat instant "rnhmcn" or Chinese noodlo nearly everyday 28.1 88.8 (53.1 *19.0 22.4 64.7 22.4* 21.0 21.0 10.8 10.8 .30.0 89.0 58.9 39.0 24.9 50.8 11.6* 20.1 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 90 percent of the patients' households affirmed it while only 31 percent of the control households did (Table S). Thus, the case-control studies clearly indicated that none of the factors tested except use ok K rice oil could account for the disease, Dosc-Reepoase Relationship To prove a causal relationship, a definite doseresponse relationship is needed. A rough estimate of the quantity of the specific Iv rice oil consumed by each patient and bis family members was made disregarding their age. 6cx, amount of food intake, and possible loss of oil during and after cooking (4). Eighty of the 140 users of the specific canned IC rice oil in question were believed to have consumed, individually, less than 720 ml. For these 80 light users, the attack rate of Yusho was S8 percent, while for those who were estimated to have used more than 720 ini, it was 100 percent (Table 9). It was also demonstrated that the 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 that of other agc-classcs. Therefore, each of the three groups of users, with different levels of oil intake, was stiuidardircd for age using the age composition of the whole 1*10 users as standard. The figures, however, hardly changed from those shown in Tabic 9. Thus, a clear doscresponsc relationship could be demonstrated, even though the estimates of the dose were inac curate (4). Toxic Agent In view of all these epidemiologic observations, rvc concluded that the K rice oil of specific pro duction or shipments had caused Yusho. Now, why was the oil toxic? The chemical study sub group (chief: Prof. H. Tsukamoto, Faculty of ' Pharmaceutical Sciences, Kyushu University) demonstrated that the canned K rice oil produced or shipped on February 5, 19G8, and used by some of the patients contained about 2,000 to Table I). Results of case-control study on oils used. Fat or oil Cttws No. of % households Controls No. of 7o households Butter Margarine Sesame oil Knpe-sccd oil ltice-hran oil Lard Other oils 35 60.7 44 63.8 21 30.5 10 14.5 66 95.7 12 17.4 13 JS.S 105 50.7 327 01.4 85 41.1 77 37.2 04 30.0 33 15.4 117 30.5 Cases: GO patient households. ' Controls: 207 non-patient households.' , '' .4 . April 1972 OSH 029202 123 H*<. it f. til n. ti- D 11 *> it ! . STLCOPCB40  Vlt i Tublc V. llclalion between ibo amount of the K rice oil used by palicnle n*i<i their clinical severity. ; ! AinOunL of Oil . Xon-aflected No. % Light eases No. % Severe cn:cs 1 6* o K 1 Total No. % r. b Less than 720 ml 720-1,440 ml More than 1,440 ml 10 0 0 (12.0) (0.0) (0,0) 39 (49.0) 14 (31.0) 3 (14.0) 31 (:m.0) 31 (09.0) IS (60.0) 60 000.0) '-J. 45 (100.0) ; 21 (ioo.o) 3,000 ppm of Kancchlor 400, (Kanegafuchi Chemical Industrial Co. Ltd.) a brand of poly chlorinated biphenyls (chlorine content: 4S%) (5). In this discovery, Prof. K. Inagami of the De partment of Food Technology, Faculty of Agri culture, Kyushu University, and his associates made most admirable contributions as members of the chemical study subgroup. Tire study subgroup also demonstrated that the oil was not contaminated with toxic agents such as Cu, Ni, Zn, Co, As, Hg and Pcnlachlorophenol. Further more, it found that most of the components of Kancchlor 400, particularly those corresponding to the peaks of higher retention times in the gas chromatograms, were retained in the sebum, subcutaneous fat, mesenteriurn, mescntcriolum, extraperitoncal adipose tissue, appendix vermiformis, heart, sternal marrow, small intestine, trachea, and other organs of patients, and can be transported into the fetus through the pla centa (o,G,7). To examine whether only the Iv rice oil produced or shipped In the period in question was contaminated with Ktfcnechlor, the chemical study subgroup analyzed 109 samples of the bottled rice oil which had been shipped between October, 1067, and October, 1968. Gas chromatographic analysis revealed that a significant contamination of tho bottled oil was limited only to those produced or shipped between February 7 to 10, 1068 (5). No analysis could be made of the bottled K rice oil produced or shipped on February 6 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 rumples of 'February 7 to 10 contained a largo amount of chlorine (maximum 462 ppm). None of the oils shipped in other months were contaminated with more than a trace amount of chlorine. Thus, tho results of chemical studies completely coincided with those achieved by epidemiologic approaches. By the way, the Kancchlor had been used at the K Company in the equipment for heating the processed oil at a reduced pressure in order to remove the odorous matters of the rice oil (Fig. 4). It is ; \ ' v ' /; (5 - ,'| .. . > Table 10. Clinical severity by age. Amount of oil used (ml) Number of patients by clinical grade . Age----------------------------------------------------------------------------------------------------------------------- Non-aflecled Light* Severo* Total <720 720-1440. * 0-12 13-29 30Total 0-12 13-29 30Total 3 (10.7) 2 (8.3) 6 (13.1) 10 (12.5) 0 (0) 0 (0) 0 (0) 0 (0) 13 (72.2) 7 (29.2) 19 (50.0) 39 (48.5) 5 (50.0) 1 (0.7) S (40.0) 14 (31.2) 2 (11.1) 15 (02.5) M (30.9) 31 (38.7) 5 (50.0) U (93.3) 12 (60.0) 3) (OS.S) 18 (100.0) 24 (100.0) 3S (100.0) SO (100.0) 10 (100.0) 15 (100.0) 20 (100.0) 45 (100.0) "Light" corresponds to grades I and 11 while "severe" to grades 111 and IV.uscd by Goto ct al. / 124 Environmental Health Perspectives \ *`u 4 DSW 029203 ,N T{*y STLCOPCB4013165 62.5 60.0 so.o V) 56.9 11.1 '\4 i.V Hoe Tr/ ' Oil 0-12 15-29 `720 hl 0-12 15-79 50 720-1.960 k. FiacmK 3. Percentage of sovere cnaes of Yuslio by ago. believed that it. must have leaked from the . heating pipe and contaminated the oil, because small openings were discovered in the old pipe. Amount of Knncchlor 400 Ingested by Patients One hundred forty-six patients who were proved to have used the contaminated canned K rice oil of February 5 and 6 by our investiga tion \yere used for the estimation of the amount of Kancchlor 400 ingested. As stated, the approxi mate amount of the oil consumed could be calcu lated for each of the patients. It 5vas on average about 800 ml. Since the' concentration of Kanechlor 400 in the oil xvas 2,000 to 3,000 ppm^ tho average amount of Kancchlor 400 ingested by a patient was estimated to be about 2 g (4). Similarly, the minimum dose of Kanechlor 400 consumed by a patient was estimated to be about 0.5 g. Babies Born to Patients and Non-afTeclcd Wives of Puticnts , 'it-. Thirteen women consisting of 11 5vith Yusho and 2 unaffected wives of patients were shown to have delivered 10 live born and two stillborn babies from February 15 to December 31, 1968 (8,10,11). As shown in Table 11, nine of them had unusually grayish, dark-bro5vn stained skin and similar pigmentation of the gingiva and nails was noted in five of them. Increased eye discharge was also notable in most of them. Histological examination of a stillborn fetus showed a marked iJ,v, hyperkeratosis and atrophy of epidermis and cystic dilatation of hair follicle, especially at the head. A marked increase of melanin pigments in the basal cells of epidermis was also noted (9). Since no such symptoms ,at birth or stillbirth has been experienced in Japan during the period in wliich their incidence among the patients was extremely high, and also since none of the mothers had had any unusual experiences, for instance, in use of drugs or in health status, these unusual phenomena could be considered to have been caused by ingestion of the contaminated oil. However, a clear dose-response relationship be tween the oil consumption and such phenomena could not be shown because of the limited number of cases. The amount of the contaminated oil consumed during pregnancy ranged from 0.3 to Rice saw Extracted with n-hexahe Defatted bran 1 Crude oil After re;oval of solvent, TREATED WITT SODIUM FtTAPHOSPHATE. ANT) CENTRlriGCD Gum" Oil Treated with IW3H MaCH layer Oil Neutralized with H^SO^ Dark oil" Sashed with hater add filtered CciCR REIWED WITH ewte porcelain clay ,,. Declcrized by HEATING AT OVER 200 C AT 3 TO 4 W ffc . 'FlIiAL products . Figure 4. Flow sheet of rico oil production. " April 1972 r OSW 029204 123 r.<' v;. >v1 :o W dr .n :y. STLCOPCB4013166 4 SB. . Iff Table 11. Babies born to patients and unaffected wives of patients and tbeir use of K rice oil. Amount of oil Pregnancy - Grade of Sex Small- Mother Ago used period clinical - Delivery of for- Stained Stained Stained No. during when oil severity . baby date skin gingiva nail pregnancy used of mother' . (L) Increased eye Neonatal discharge jaundico 1 28 0.3 3rd 2 Normal M No 7 -- trimester 2 24 t 7 3 Normal F No 3 22 1.4 Later half Normal Forcop M No + 7 -- of 2nd trimester 4 27 0.7 2nd 1 Normal M Yes + + -- trimester 6 26 0.7 1st 3 Normal F No 4- + 4 trimester 6 29 1.4 Later half 3 Normal M No + + of 2nd trimester 7 30 1.1 Whole 8 23 r Whole 9 33 7 7 1 Normal M Yes + -- 3 Norma! M 30 + -- 7 Caesarean M Yes 4 4 4 section 10 20 0.3 Enrly half Normal Norma! F No 7 of 2nd trimester 11 20 ? 7 2 Normal M No + + + 12 33 2.6 Early half 4 Stillbirth 7 7 + 7 7 of 2nd trimester 13 25 7 ? 3 Stillbirth F Yes + ? 7 --+ ++ + 44 +7 4- + ++ +7 + .4 47 + ++ Table l$r Prognosis of pulients with Yuslio.* Crude of clinical soverity** -- Improved . Clinical conditions Stational Worsened 0 16 (66.7) 1 30 (51.7) 2 * 23 (52.3) 3 12 (52.2) 4 0 (0) Total 81 (50.0) 6 (25.0) .16 (27.0) 16 (30.4) 10 (43.5) 10 (100.0) 58 (36.6) 2 (8.3) 12 (20.7) 5 (114) 1 (4 3) 0 (0? 20 (12.6) Culcubitcd from the figures reported by Toshitar.i and Kitamura. * 0: Physical complaints without skin-lesions. 1: Pigmentation of tho skin and the mucous membrane. 2: Comedo formation. . 3: Acneform eruptions', " 4: Extensive distribution of acneform eruptions. Total 24 (100.0) 58 (100.0) 44 (100.0) 23 (100.0) 10 (100.0) 159 (100.0) 126 Environmental Health Perspectives DSW 029205 STLCOPCB4013167 rr J. itfV u i'.v . 2.G liters (Tablo 11) (S). Twelve of 13 fetuses were smaller than the national standards, and 4 involving more than two million chickens in the western part of Japan (15,18). More than of them were small-for-dates babies (S, 10). As 400,000 chickens were reported to have died. The '?' they grew older, the stain in their skin grudually 6 i faded (11). No evidence has so far been obtained i. .v.- with regard to any physical and mental retarda ! tion of the babies, but we suggest that a par rI,i**l"\ ticularly careful and prolonged follow-up observa tion should be maintained for their future (8). disease was characterized by such clinical signs ns labored breathing, droopincss, rufilcd feathers, high mortality and decreased egg production (15,IS). Autopsy revealed a marked subcu taneous edema, hydropericardium, ascites, and pulmonary edema, muscular ecchymosis in tho I" Growth of Affected Children thorax or inside of the thigh, and yellowish mottled appearance of the liver (15,17,IS). An '.! > To examine whether Yusho disturbs children's i'l', \ growth, tho affected school children, 23 boys and 10 girls, were compared in 1967, 196S, and I960 ' .. with their 719 healthy classmates matched by ,v ! sox. The gains of tho affected boys in both height and weight decreased significantly after tho ' poisoning, while tho affected girls showed no <-; definite change in this respect (12). cpizootiological investigation demonstrated that the disease was caused by feeding chickens with specific lots of commercial brands of formula chicken feeds manufactured by two companies. In view of the fact that the K rice oil used by Yusho patients had been contaminated with Kanechlor 400, the toxic feeds were analyzed for chlorinated hydrocarbons and proved to contain Ivanechlor 400 (16,19,20). The experimental Current Stale of Pa Lien ts reproduction of the disease by administering this chemical mixture was successful (10,20,21). The More than 3 years have passed since the reason the chicken feeds were contaminated with epidemic was reported. It is a heart-breaking fact Kanechlor 400 could be reasonably understood that many patients with Yusho are still tortured by the following facts: both of the chicken feed by the sickness because no curative treatments manufacturers had been using "Dark oil" pro have been discovered yet. In summer of 1970, a t t* ' Mv` . mass clinical examination of the Yusho patients was carried out in Fukuoka-Ken, and the clinical duced by the K company (Fig. 3) ns an ingredient of their formula feeds, and they had actually used "Dark oil" purchased from the company from state of the patients examined were compared February G to 27, 19GS. The remaining sample of *'c * with their previous findings observed in summer "Dark oil," used for production of tho toxic of 19G9. As shown in Tuble 12, about a half of the V formula feeds, was also shown to contain about 159 patients, for whom the comparison was 1,300 ppm of Kanechlor 400 (10,20). Thus, it feasible, were shown to have clinically improved became clear that both the epidemic of Yusho ; signs, while the remaining half showed no such and the epizootic of the disease among chickens favorable signs, and more than 10 percent of the had been very closely associated, being enused patients were even worsening (13). It should bo by intake of the oils contaminated with Kane Uv noted, furthermore, that even many of those who appeared to be clinically improving had several chlor 400. It is very unfortunate, however, that the epidemic of Yusho could not. have been pre serious complaints, such as persistent headache, vented even though a largo scale epizootic of general fatigue and feeling of weakness, numbness 6uch an unusual chicken disease had preceded f-- in limbs, weight loss, and others (14). All these `.s facts clearly indicate that recovery from Yusho is the incidence of Yusho by more than G months. extremely difficult. To cure them as quickly as possible and to prevent another epidemic of HEFEUENCES Yusho, all possible world-wide cooperative efforts arc highly desired. From the middle of February to the end of March, 19GS, an epizootic of a strange disease closely resembling chick edema disease occurred 1. Katsuki, S. 10G0. Foreword, Iti-ports of tho Study Group for "yusho" (Cldorobiphcnyls Poisoning), Fukuoka Acta Mod. 00: 103. 2. Kuratsunc, M. ct id. I9G0. An epidemiologic study on "Vusho" or cldorobiphcnyls poisoning. Ibid. CO: 613. 3`. Goto, M. and Higuchi, K. 1009. The symptomatology *. , fJ April 1972 DSW 029206 127 54 M :x STLCOPCB4013168 >.i "+./, . ''*+ 'ki 'low** *>. UuJi^ -A'af^Wj * of Ynslio (chlorobiphcnyls poisoning) in dermatology, further study of its dermatological findings. Ibid 62: Fukuoka Acta Med. CO: 400. 132. 4. Yoshimura, T. 1971. Epidemiological analysis of "Vutho" patients with special reference to sex, ngo, clinical grades and oil consumption. IbidJ>2: 101. 5. Tsuknmoto, 11. ct al. 1909. The chemical studies on detection of toxic compounds in tho rice bran oils used , by the patients of Yusho, Ibid 00: 490. C. Kojimo, T. 1071. Chlorobi[>hcnyls in tho sputa und tissues. Ibid 02: 25. 7, Kijuchi, M. ct al. 1971. Two autopsy cases of chronic chlorobiphcnyls poisoning. Ibid 02: 89, 14. Okumura, M., llirnvnma, C. and Uzawa, M. 1971. Study of Yusho (rhlorohiphcnyls poisoning) in clinicg) examination. Ibid 02: 123. 15. Kobanawa, M. el al. 1009. Poisoning due to nn oily by-product of ricc-hinn similar to chick edema disease. I. Occurrence mi l toxicity test. Natl. Inst. Anim. Health Quart. 0:213. 10. Kohanuwa, M. cl nl. 19C9. Poisoning due to nn oil by-product of rice-bran similar to chick edema disense. II. Tctraciilorobiplicnyl ns toxic substance. Ibid 9: 220. 17. bhoya, S. Cl al. lb'Vk Pathological changes of poisoning 8. Ynmnguchi, A., Yoshimura, T. and Kurntsunc, M. in chickens due to dark-oil, an oily by-product of rice 1971. A survey on pregnant women having consumed bran. Ibid 9: 229. rice oil contaminated with chlorobiphcnyls and their 18. Kogn, K. cl nl. 1970. btudio.x on the toxic principle in babies. Ibid 02: 117. n certain by-produrl of rice oil rendering. I. Toxicities 0. Kikuclii, M. ct ah 10G9. An autopsy case of stillborn of on the chick. Japan. J, Zonlechnical Sci. 41: 330. chlorubiphenyls poisoning. Ibid 00: 489. 19. Kogn, K. cl nl. 1970. Studies on the toxic principle in 10. Taki, I., Hisanoga, S. und Amngnsc, Y, 1909. Report a certain by-produrl of rice oil rendering. II. A survey on Yusho (chlorobiphcnyls poisoning) pregnant women of u toxic fiubstanrr'. Ibid 41: 439. and their fetuses. Ibid 00: 471. 20. Kogn, K. ct nl. 1971. Studies on the toxic principle in 11. 1'unnl.au, I. ct nh 1071. A chlorobiphcnyls induced acertnin by-product of rice oil rendering. HI. Toxicity fetopathy. Ibid G2: 139, of chlorinated biphenyl on chicks and summarized 12. Yoshimura, T. 1971. A case control study on growth results of 1-1II. H id 42: 10. of school children with Yusho. Ibid 02: 109. 21. Goto, K., Sakogurhi, K. mid Ogawa, K. 19G9. Hydro- pi! 13. Toshitani, S. and Kitnmurn, K. 1971. Ciinicnl observa poricnrdiiirp assay of rice oil which caused Yusho and tion of Yusho (chlorobiphcnyls poisoning), especially of Ivanochlor 400 in chickens. Ibid 00: 533. '.U iiij n`H. M .!* 128 DSW 029207 Environmental Health Perspectives r\v*<-:rFr> 3HT STLCOPCB4013169