2/4/212 N.N. lexandrov National Center of Belarus Does an occupation at a tannery promote pancreatic cancer? Ilya Veyalkin, PhD Minsk Tannery Enterprise is one of the biggest in the world. Many peoples have been involved into leather production in the last 5 years. Many chemicals with proved or suspected carcinogenic or mutagenic ability are used in the tanning cycle. They are: formaldehyde, surface-active substances, benzidine and aniline dyes, oxidising agents and chromium compounds, leather dust and also such traumatic agents as sulfuric and hydrochloric acids, ammonia, organic solvents, sulphite and sulphide anions. Moreover the main strategy of leather production is to use the most hydrophobic reagents for the deepest skin impregnation, but it also facilitates their penetration via natural barriers of the human organism. Enterprise can be divided into three main parts: leather tanning, painting and decorating workshops. im Investigate the possible relation between cancer mortality and tannery occupation Methods The cohort of 3468 workers who were actively employed with a minimum of 6 months was retrospectively followed from 1 January 1953 to 31 December 2 to calculate proportional mortality ratios (PMRs). 768 workers (328 women and 44 men) were died from different causes. The same cohort was additionally investigated by proportional cancer incidence ratios (PIRs) for 196-27 (262 cancer cases). ge and time standardization was implemented. MLES (N=1877) PIR=O/E x 1% MINSK TNNERY RCHIVES REDUNDNT WORKERS (1953-1995) MINSK CIVILIN REGISTRY RCHIVES (768 DECESED WORKERS) MINSKCNCER REGISTRY (175 CNCER CSES) STUDY COHORT PMR=O/E x 1% REFERENT POPYULTION MINSK POPULRION (1953-27) MINSK CIVILIN REGISTRY RCHIVES MINSK CNCER REGISTRY MINSK CITY STTISTICS DEPRTMENT FEMLES (N=169) Standardisation by SEX, GE and TIME 1
ge, years 2/4/212 NH 4 SO 4, NH 3, pancreatic enzymes, Cr(III), Cr(VI), H 2 SO 4, formaldehyde NH 3, aniline dyes, formaldehyde, chromate gelatine, nigrosine, ethylcellulose, acetic & formiatic acid. Nitrolacquers, butylacetate, ethanol, fish fats, waxes, latex, petroleum oils, alizarin, glycerin, spindle oil, acrylic emulsions. Leather dust could accumulate all polutants FOUR STUDY GROUPS WERE CONSIDERED WORKERS OF LIMING ND TNNING WORKSHOPS (87% males & 13% females) WORKERS OF DYEING, STUFFING ND DECORTING WORKSHOPS (2% males & 8% females) DMINISTRTION TEM (85% males & 15% females) LL PEOPLE OCCUPIED T THE TNNERY (54% males & 46% females) We analyzed cohort in different ways BY SENIORITY: occupied less than 1 year; From 1 till 3 yrs; from 3 till 6 yrs; from 6 till 1 yrs; from 1 till 2 yrs; from 2 till 25 yrs; more than 25 yrs; more than 2 yrs; more than 1 yrs. BY TIME OF STRT WORKING: Hired till 195; Hired from 1951 till 196; Hired from 1961 till 197; Hired from 1971 till 198; Hired from 1981 till 1994 inclusive. BY DTE OF DISCHRGE: Discharged since till 196 inclusive; Discharged since 1961 till 197; Discharged since 1971 till 198; Discharged after 1981 inclusive. 9 8 7 6 5 4 3 2 1 MEN GE OF DETH Workers Males Workers Females Population Males Population Females Time 1957-61 62-66 67-71 72-76 77-81 82-86 87-91 92-96 97-21 EXTERNL & UNKNOWN 21% Main causes of deaths in the cohort of workers OTHER 12% CNCER 2% Males VSCULR 47% EXTERNL & UNKNOWN 1% OTHER 12% Females CRDIO- CRDIO- VSCULR 52% 2, 15, 1, 5, 99,1 Proportionate Mortality Ratios for workers died of main causes 93,4 9, 13, 15,6 17,8 121,1 98,5 CNCER 26%, Cardio-vascular diseases Malignant neoplasms External and unknown Respiratory diseases males females 1% level 2
2/4/212 PMR% 6 5 4 161 3 47 2 1 69 PMR For Workers (males) Died of 23 11 13 195 59 122 87 3 461 51 21 45 135 62 9 Lip, oral cavity, pharynx Esophagus Stomach Colon and intestinum Rectum Liver, Pancreas, Gallbladder and mesentery Pancreas Larynx Lung, bronchuses and trachea Bones and a cartilaginous tissue Melanoma and skin Breast Prostate Others of males genital Kidney and Bladder Not specified localizations PMR% 9 8 7 6 5 4 3 2 1 PMR For Workers (females) Died of 84 7 77 167 313 116 318 98 173 87 169 93 53 13 Stomach Colon and intestinum Rectum Liver, Pancreas, Gallbladder and mesentery Pancreas Lung, bronchuses and trachea Melanoma and skin Breast Corpus and cervix uteri Others of females genital Kidney and Bladder Not specified localizations Blood and limphatic system Localization Blood and limphatic system Total cancer Localization Total cancer 18 16 14 12 1 8 6 4 2 Significantly High PMR for Females Pancreatic ( - p<,5) O=8 O=6 O=5 O=5 O=5 O=7 313 1 366 1 Dyeing- Stuffing & Decorating Workshops 418 1 858 Seniority Seniority 1- More Than 2 yrs 1 yrs 724 654 1 1 1 Started 1961-198 Occupied 1961-1984 14 12 1 8 6 4 2 PMR for Females Melanoma and Skin s ( - p<,5) 32 O=4 O=4 O=3 O=4 455 497 44 Dyeing-Stuffing & Seniority More Than 1 Decorating Workshops yrs Started Before 197 3 25 PMR for Males Melanoma and Skin ( - p<,5) 7 6 PMR for Cervix and Corpus Uteri s ( - p<,5) 2 15 195 O=3 O=2 O=2 129 5 4 3 2 O=12 O=9 O=6 O=6 O=7 339 287 29 165 177 1 5 3 dministration Seniority 6-1 yrs 1 Dyeing-Stuffing & Decorating Workshops Senirity 1-2 yrs Started Before 195 Fired Before 196 3
Concentration Cr3+ (g/l) 2/4/212 ( - p<,5) Dependence of PMR on Tannery Females Workers Seniority (for Total s) 25 2 15 O=3 1 5 <12 12-36 36-72 72-12 12-24 24-3 >3 Males Seniority (months) Females 25 2 r Spearman 1.( p,5) R 2 =,9348 15 1 5 36-72 72-12 12-24 24-3 >3 Seniority (months) Latest tanned Stained with NDR Stained with CEBU sediment Dust Sample HClpepsin Pancreatin ph=1, T=38ºC FILTRTION ph=9, T=38ºC FILTRTION EXTRCT 1 EXTRCT 2 Cromium III? + Formaldehyd? - niline? - Phenol? - C H E M I C L N L Y S I S 1-pepsin digestion 2-pancreatin digestion 1,4 1,2 1 1 g DUST 24 mg Chromium III EXTRCT imes test,8,6,4,2 HCl-pepsin Pancreatin Total Latest tanned NDR CEBU Salmonella typhimurium T 1 NO MUTGENICITY 4
2/4/212 PIRs For Workers (males) (ICD 1) Obs. Exp. PIR 95%CI- 95%CI+ 23,3 LUNG (C34) 41 176 126 239 STOMCH (C16) 14 14,3 98 54 164 COLON (C18) 6 5,1 118 43 256 PNCRES (C25) 6 2,8 214 79 466 LRYNX (C32) 4 3,8 15 29 27 SKIN (C44) 4 1 4 11 12 BLDDER (C67) 4 4,9 82 22 29 KIDNEY (C64) 4 4,2 95 26 244 BRIN (C71) 2 1,6 125 15 452 FLOOR OF MOUTH (C4) 2,7 286 35 132 OTHER ND OF NON-HODGKIN'S LYMPHOM (C85) 2 1,3 154 19 556 OTHER CONNECTIVE ND SOFT TISSUE (C49) 2,7 286 35 132. But considerably high level of pancreatic cancer was noted in males workers (PIR=298%; 95%CI=11-65), who were employed in DSW for more than 7 years in 7th - 8th. HYPOPHRYNX (C13) 2,5 4 48 1445 OESOPHGUS (C15) 2 1,9 15 13 38 PROSTTE (C61) 2 7 29 3 13 RECTUM (C2) 2 3,6 56 7 21 PIRIFORM SINUS (C12) 1,4 25 6 1393 RETROPERITONEUM ND PERITONEUM (C48) 1,3 333 8 1857 MELNOM OF SKIN (C43) 1 1,1 91 2 57 TONSIL (C9) 1,3 333 8 1857 RECTOSIGMOID JUNCTION (C19) 1 1 1 3 557 TESTIS (C62) 1 1 1 3 557 TOTL 17 PIRs For Workers (females) (ICD 1) Obs. Exp. PIR 95%C 95%C I- I+ BREST (C5) 3 26,9 112 75 159 SKIN (C44) 21 25,2 83 52 127 STOMCH (C16) 14 14,3 98 54 164 CORPUS UTERI (C54) 11 11,1 99 49 177 CERVIX UTERI (C53) 1 7,9 127 61 233 LUNG (C34) 8 5,1 157 68 39 MELNOM SKIN (C43) 7 2,4 292 117 61 COLON (C18) 7 9,7 72 29 149 THYROID GLND (C73) 6 3,8 158 58 344 OVRY (C56) 6 6,8 88 32 192 PNCRES (C25) 5 3,4 147 48 343 KIDNEY (C64) 5 4,4 114 37 265 OTHER ND UNSPECIFIED TYPES OF NON-HODGKIN'S LYMPHOM (C85) 3 1,3 231 48 674 HODGKIN'S DISESE (C81) 2,86 233 28 84 OTHER ND UNSPECIFIED PRTS 2,8 25 3 93 OF BILIRY TRCT (C24) MYELOID LEUKEMI (C92) 2 1,3 154 19 556 MULTIPLE MYELOM ND MLIGNNT PLSM CELL NEOPLSMS (C9) 2 1 2 24 722 BLDDER (C67) 2 1,7 118 14 425 RECTUM (C2) 2 5,8 34 4 125 LIP (C) 1,5 2 5 1114 DIFFUSE NON-HODGKIN'S LYMPHOM (C83) 1,4 25 6 1393 OTHER ND UNSPECIFIED PRTS OF TONGUE (C2) 1,2 5 13 2786 RETROPERITONEUM ND PERITONEUM (C48) 1,6 167 4 929 MESOTHELIOM (C45) 1,3 333 8 1857 RECTOSIGMOID JUNCTION (C19) 1 1,9 53 1 293 TOTL 155 Conclusions Workers occupied in Dyeing-Stuffing and Decorating workshops has higher risk to die with pancreatic cancer (PMR). Time related analysis suggested that the most favorable for pancreatic cancer conditions were before 1962-1964 and before 1978-84. In these years the tannery worked in full operation and used formaldehyde and some Direct Black 3 azo-dye. majority of workers who died with pancreatic cancer were either driers (high formaldehyde exposure) or painters (high dye and solvents exposure). Leather dust was presented in all places. nalysis of leather dust has shown huge extrication of Chromium III compounds and dyes but not phenol, aniline and formaldehyde after enzymatic digestion. Conclusions Just non-significant excess in pancreatic cancer incidence both in males (PIR=214 (79-466)) and females (PIR=147; (48-343). but considerably high level of pancreatic cancer was noted in males workers (PIR=298%; 95%CI=11-65), who were employed in DSW for more than 7 years in 7th - 8th. Significant excess in PIR for lung cancer was established in males workers (PIR=176 (126-239)). Significant excess in PIR for melanoma of skin was established in females workers (PIR=292 (117-61)). N.N. lexandrov National Center of Belarus p/o Lesnoy-2, 2234, Minsk area, Belarus, tel. +375(17)269 95 5, E-mail Oncobel@omr.med.by, www.omr.med.by 5