Document 4445RNwXxYx0vqqxn1E4Xm7vV

W einberg Consulting Group Inc. 2828 Pennsylvania Avenue NW, Suite 301 Washington, D.C. 20007 (202) 342-6513 LAWYERS1WORK PRODUCT PRIVILEDGED AND CONFIDENTIAL O ctober 31, 1983 Dr. William Gaffey Building "G" Monsanto Company 800 N. Lindbergh Boulevard St. Louis, MO 63167 Dear Bill: I am sure th a t you have seen the enclosed. Do you consider this as unique or are there other such reports which im plicate working in a chlorophenol-producing and/or -using plant with lymphomata? I would like you thoughts on this if you have the tim e. Thanks for your help on this. Very truly yours, WEINBERG CONSULTING GROUP Inc. Myron S. Weinberg, Ph.D. MSW/vh Enclosure SUBJECT TO PROTECTIVE ORDER. 626. - - ' _ -- 16 1978THE LANCET, SEPTEMBER ,' extremities (10%), unspecified <fcbility'(3%), and speech trou TA99 - - ` TA100 bles (2%)'. Combinations of disabilities were common. There. - was-considerable variation, between the assessment made by - the g.p.', the district nursing services, and the-geriatric depart- raent regarding the incidence of these types of disabilities.'The numbers citedxorrespond to the'assessment made by-the geri- - atricdepartment. Two-thirds of the referred pensioners wished for, or at least contemplated, a change of accommodation. Requests for allo cation of accommodation in nursing-homes were met in about 50%`of the cases, whereas only 23% of the requests for shel- tered housing were met. After assessment, treatment and pro vision of necessary 'services-and improvements in living condi tions it was decided, in 51% of cases,'that the referred pensioner could and should remain at home. ~ . . Almost all of the pensioners had been referred because of imminent of established breakdown in their ability to cope in dependently in their own homes. The figures demonstrafe that geriatric assessment and consequent action help many elderly people to. continue independent living outside institutions '-- and such' assessments reduce (by half)the need for insti Muxageok activity of extract! of salted fih- o bacteria without 5-9 mix; bacteria with 5-9 mix; A bacteria with 5-9 mix and YahagiV4procedure. tutional care for frail elderly people. and body-weight). The test animals were fed daily with .M id d d fin Sygehus. ` 5500 Middelfan, Denmark R. KRAKAUER steamed cooked salted fish and fresh water, whereas the con trol rats were given fresh water and animal chow salted to the concentration found in the salted fish; Pooled urine from each SALTED FISH AND NASOPHARYNGEAL ' CARCINOMA IN SOUTHERN CHINESE pair of rats was concentrated about a lOOrfold/345dissolved in 4 ml dimethylsulphoxide, and subjected to the Ames test. Mutagenic activity for both TA100 and TA98 was found in S ir ,-- The unusually high incidence of nasopharyngeal car all the salted-fish preparations tested and all showed a dose- cinoma (n.P.c.) in southern Chinese both in and outside China' responsive curve (see figure). Since TA 100 and TA98 detect has been known far over fifty years and is thus likely to be the different mutagens, there was probably more than one product of a traditional environment pecutiar to southern mutagen in the preparations tested* In most cases mutagenic Chinese. The age-specific incidence curves for southern activity was enhanced by liver microsomal activation, and in Chinese of both sexes rises steeply after the age of 19-24 yean. some cases also by prcincubating the bacteria with-S-9 mix at Ho,1*' 1-has suggested that the etiology involves ah interaction 25C for 20 min before the test.16This procedure causes selec between a genetically determined susceptibility, early infection tive enhancement of the activity of N-nitroso compounds, sug by the ubiquitous Epstein-Barr virus (e.b.v.), and consump tion of a traditional preserved food by southern Chinese from early childhood. Salted fish, a traditional food frequently con gesting that some of the mutagens in the samples tested are N-nitroso compounds. Mutagenic activity was also found in urine from the experi sumed during weaning and post-weaning periods, contains a mental rats with a dose-response relationship. variety of volatile nitrosamines/"6 compounds which induce Our findings may explain the induction of carcinoma in rats tumours in the nasal cavities and/or nasopharyngeal tube in animals.789'*0 Carcinomas appeared in the nasal cavity and maxillary sinus of 4 of 22 albino rats fed salted fish for 12-24 fed with salted fish16 and the high incidence of n .p .c . in south ern Chinese, although one must be cautious in extrapolating events in animals, especially under experimental conditions; to months (ref. 11 and unpublished). We have applied the Ames mutagenicity test1112using the TA100 and TA98 strains of SaimoneHa typhimurium and mammalian microsomal (S-9 mix) activation to extracts of salted fish and to the urine of albino rats which had consumed such fish. Salted-fish extracts were prepared by mincing and suspension in dimethylsulphoxide (2 ml/g of fisb) with the human situation. We thank the World Health Foundation -Hong Kong) and the Hong Kong Anti-Cancer Society for financial assistance. Medical and Health Depanmem, Institute of Radiology and Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong T U r 1 Hn . J . M. U-- n o D . P . HCANG vigorous- shaking for 24 h and centrifugation at 10.000 rev/ min for 10 min at room temperature. The Ames test was done Department of Biochemistry, University of Hong Kong ' Y . Y . FONG with the supernatants. Urine samples were collected for 72 h from 4 pairs offish-con suming rats and 4 pairs of controls (matched for sex, age FAMILIAL AND SPORADIC HODGKIN'S DISEASE ASSOCIATED WITH OCCUPATIONAL WOOD : EXPOSURE - 1. Ho, H. C..J. R. CoipSurg. Edin. 1975*. 20, 223. _2. Ho,-H. C. in Cancer in Alia, Opportunity for Prevention, Detection and Treatment. Gann Monograph on Cancer Research no. 18. p. 49. 1974. 3. Ho, J. H. C. tn l.J. Radial. Oncol. Biot. P4vj. 1978,4, 181. . 4. Fong, Y. Y.,Chan, W .C .Saturt, 1973.243, 421. 5. Fong, Y. Y.. Chan. VC\ C. Fd Cotmet. Toxical. 1976,14,9S. 6. Huang. D. P., Ho, J. H. C,, Gough, T. A., Webb, K. S .J. Food Safety, 1977, 1| k . 7. C arin a , A.-, Poux. P., Haai, H., Althoff. J., Mohr, l '. Cancer, 1976,37, 346. 8. Althoff, J., Mohr, L'., Page, N., Reznik, G. 7, natn Cancer init. 1974, S3, 795. 9. Pdur, P.. Kruger, F. W,, C a rin a , A.. Althoff, J., Mohr, U. J. natn Cancer Inu. 1913.1,1019. 10. Haai, H., Mohr. U., Kruger, F. W .J.nain Canter Intt. 1973,31, 1295, 11. Huang, D. P., Saw, D , I eoh, T. B., Ho, J. H. C, Paper prevented at the International Symposium on Etiology and Control or Nasopharyngeal Carcinoma in Kyoto, April 1977 to be published;. 12. Ames,B. N.,McCann, J.t Yamasaki. E.,,lfuwf. Ret. 1975.31,347. S ir ,--The aggregation of Hodgkin's disease in communities and families has suggested the influence of environmental risk factors, particularly of an infectious nature/ Evidence implicalling industrial-or chemical agents has been scarce, although an excess risk has been reported among woodworkers1 1 and organic chemists.6 An occupational exposure may have contributed to a fami- 13. Yamataki, E ,, Amct, B. N. Proe. tatn Acad. Sei. U S A .. 197?, 74, 3555. W. Yahagi, T,, Nagao, M., Scino, U-, Mauuihima, T ,, Sugimura, T .. OkaJa, M. Aiutar' Ree. 1977,4S, 121. 1. Guteniohn, N., Cole. I*, lju. J. Cancer, -1$77,19, 595. 2. Milham, S., H nicr, J, E, Lancet, 1967, ii, 136. 3. Grurferman, S., Duong, T.r Cole, P. J . natn Cancer tn u . 1976, 37, 1193. 4. Olin, R. Lancet, 1976, n, 916. - CONFIDENT? SUBJECT TO- PROTECTIVE ORDER. C23814 *- THE LANCET, SEPTEMBER 16,1978 627 DEFICIENCY LEGEND I MALE HODGKIN S DISEASE NS - NODULAR SCLEROSIS MC - MIXED CELLU LARITY C fem ale, other cancer 11 SIBS, SEX NOT SPECIFIED lumbering, with a relative mk of 4-2 (95% confidence Interval. . 1-4-12-5). Reports of Hodgkin's disease among workers in the wood in dustry have stimulated interest in various physical properties of wood.* \ l n the family under study, -there was conspicuous exposure to chemical preservatives, notably p .c .p ., which is ex pensively used in the lumber and wood industry (1969 world production 2-1 x 10* kg). However, only two of the four family members with Hodgkin's disease were occupationally exposed, suggesting the interplay between genetic and environmental determinants, as illustrated by the susceptibility to radiogenic cancers among persons with xeroderma pigmentosum, bilateral retinoblastoma, or the basal-cell nxvus syndrome.' However, p.c.P. easily escapes from the workplace into the general en vironment,* 10-especially water supplies* and is present in the urine of occupationally exposed and "normal" individuals.-*1 P.C.P. is not known to be carcinogenic, but data are limited and commercial preparations, usually contain structurally related compounds, like dioxin, which is carcinogenic in rodents.12 Since p .c .p . is applied to lumber at many stages in its pro cessing, beginning at the sawmill, unrecognised exposure may occur among many wood-utilising occupational groups. Thus, it may be that the association between occupational wood exposure and Hodgkin's disease (and perhaps nasal cancer) is related to the use of particular chemical preservatives. We thank Dr Lyle Wong of the Hawaii Epidemiologic Studies Pro gram for p .c.p . deierminaiions on paueni III-3. % 1681 AGE AT DIAGNOSIS / DECEASED Pedigree of a familial Hodgkin's disease kindred (N.C.I. Epi demiology Branch no. 329). lial occurrence of Hodgkin's disease affecting three sibs and a first cousin (see figure). All cancers reported were histologically verified. Except for one child with isolated IgA deficiency (IV-1), detailed laboratory investigation of family members showed no abnormalities of immune function, chromosome structure, or Epstein-Barr virus litre. Two brothers with Hodgkin's disease (III-3, 4) had been employed by a fenceinstallation company for 15 and 12 years, respectively, and worked primarily with cedar wood products immersed in a fungicide/insecticide solution, pentachlorophenol (p .c .p .). The brothers prepared and applied the preservative solution by hand, without protective clothing, and the one sib still employed at the time of study had high levels of p .c .p . in the serum (1299 p.p.b.) and urine (90 p.p.b.). There were no simi lar exposures in the remaining two familial cases. Hodgkin's disease (nodular-sclerosis type) also developed in an unrelated 31-year-old employee of the same company (average number of workers 15). Since a positive association between woodworking and Hodgkin's disease has not been consistently observed, we examined the occupational statements on death certificates in North Carolina counties with a significant proportion of the population employed in furniture-manufacturing and lumber ing. In an earlier study,5this approach was used to confirm the relationship between nasal cancer and woodworking pre viously reported in the U.K. Between 1956 and. 1974, there * were 167 deaths from Hodgkin's disease among white males. To each case, two control certificates chosen from other causes of death were matched by sex, race, county of death, age, and year of death. An excess risk was found only among occupa tional groups with wood and paper exposure. Matched triplet analysis'revealed a relative risk of 1-4 ( 95% confidence interval 0-8-2-3). The major difference occurred for carpentry and Environmental Epidemiology Branch. National Cancer Institute, ~ Bethesda, Maryland 20014,1'.S.A. Providence. Rhode Island - M arx H . G reene L ouise A. B rtnton Joseph F. F raumeni R ic h a r d D 'Am ic o CHROMOSOMAL DAMAGE AND HAIR DYES Sir,-- Having been asked by a U.S. Congressional com mittee to evaluate the quality of certain epidemiological studies of the possible carcinogenicity of hair dyes 1 read the July 15 paper by Dr Kirkland and colleagues (p. 124). For teaching physicians about research methodology and biostatistics this report could be used as a "museum of pathology", displaying a plethora of violations of fundamental scientific principles. (1) The study cannot be reproduced because the procedure used to obtain the two groups under investigation is not described, except for a statement that they were "volunteers" . (2; In most such studies the number of controls equals (and often exceeds) the number of cases Kirkland ei al. do not explain why they compared 36 controls and 60 hair timers (3 i Having designed a study to test a hypothesis about ihe effects of hair dyes on unters and non-unters Kirkland et al. analysed the data and found no difference in the two groups. They then defined a new hypothesis, and, using ihe same data, consirucied new sets of cases and controls. The results of-this post hoc act of hypothesis gener ation are presented and interpreted as though they emerged from a valid a n of hypothesis testing. (4) The authors examined 100 cells m all of 96 people. 1 would expect the results to be expressed in terms of damaged people, but all the data are shown only for the 9600 cells counted. J 32 chromatid breaks in 2800 cells of a group of 28 subjects (mean 0 047 breaks per cell) does not tell us whether 2 subjects each had 66 breaks and 26 had no breaks or whether the 28 subjects all had 4 or 5 breaks.-Further more, the subsequent statistical analyses are improperly conducted as 6. Robinson,T. Lancet, 1972, il. 771 - 7. Sabine. J. R., Horion, B J., Vt icks, -M B. J. nam Cancer Insi. 1973,*0, - 1237. - - -* 8 $troog. L C. in Genetics of Human Cancer teditedby J. J Mulvihill, R. IX'. Miller, and J. F Frauroenihp 401. ' 9. Norup, B \l'*4cr fies.1972, i, 1585. *- -? 10 Fouoiame.J F... Joshipura. P B , Keliher, P. N-ebid. 1976,10, 183-. 11 Cranmcr, M., Freal, J LifeSci. 1970,9, 121 12- Van Miller, J P., Law lich.f. Allen, J R. CAemoi/>/iere( 197?,, 625 -- 1 1 ! * I ! I !