the interaction between occupational and smoking and its relationship to lung

L. On the interaction between occu pational arsenic exposure and smoking and its relationship to lung cancer. Scand j work environ health 7 '(1981) 302-309. The interaction between occupational arsenic exposure and tobacco smoking and its relationship to lung cancer mortality among 228 deceased Swedish copper smelter workers was studied with the case-referent techni que. Arsenic exposure was assessed via detailed company records, and information on smoking habits was gathered from the next of kin. The age standardized rate ratio for death from lung cancer was 3.0 for arsenic-exposed nonsmokers and 4.9 for smokers without occupational arsenic exposure in relation to nonarsenic-exposed nonsmokers. For arsenic-exposed smokers the rate ratio was 14.6, indicating a multiplicative effect of the two exposures. Eighty-five percent of all deaths from lung cancer among the smelter workers could be "explained" by arsenic exposure and/or smoking. The inter action between arsenic and smoking suggests that a strong preventive effect on lung cancer incidence could be obtained by decreasing either one of the exposures or by disaggregating them.

Exposure to inorganic arsenic compounds has been associated with an increased mortality from lung cancer among copper smelter workers (12,25,33), pesticide production workers (9,15,21), and vintners (8,29). In several of the studies positive dose-response relationships were indicated. Investigations on Swedish copper smelter workers have revealed an increased risk of lung cancer (23), especially among workers exposed to arsenic (2,34).
The interaction between tobacco smoking and occupational exposures can sometimes be fit to a multiplicative model, in which the effect, eg, increase in lung can-0355-3140/81/040302-8 cer incidence, on workers who are smokers can be estimated by the multiplication of effects in nonexposed smokers and exposed nonsmokers. This type of interaction has been observed in asbestos factory and insulation workers (4, 31), and in uranium ore miners (1). In other instances the multiplicative model is not applicable, eg, among zinc-lead miners (3) and workers exposed to chloromethylethers (35). Two studies on American copper smelter workers exposed to arsenic did not give evidence of a positive interaction between smoking and smelter employment (not further specified) on lung cancer mortality (25,26). However, no detailed analysis of the arsenic-tobacco smoking interaction was performed.
A peculiarity with arsenic carcinogenicity is the discrepancy between epidemiologic and experimental data. Animal carcinogenicity tests have been negative except for some preliminary data indicating a role of arsenic in the development of lung cancer (10) and leukemia (20). Arsenic is not mutagenic in bacterial tests (13, 28).
On the other hand, there are indications, from different experimental systems, that arsenic may interfere with deoxyribonucleic acid (DNA) repair, and therefore a cocarcinogenic effect is possible (11,27).
The purpose of the present investigation was to elucidate the arsenic-tobacco smoke interaction among workers from a large Swedish copper smelter. It was anticipated that the results would give practical guidance for minimizing the risks associated with occupational exposure to arsenic, as well as provide insight into the mechanisms of arsenic carcinogenicity.

Source of subjects
The study was performed according to the case-control or case-referent technique within a cohort. The cohort included all male workers employed at least three months at the Ronnskarsverken copper smelter since the start of operations in 1928 until 1 January 1967 (34). It consisted of 3,958 subjects who were followed until 1 January 1977, and all but 1 Ufo were traced. Data on the causes of death among the 953 workers who had died before this date were obtained from the National Register on Causes of Death. This register contains information from death certificates, which have been shown to be of high validity for most diagnoses (6).
The cases constituted all men who had died from cancer of the trachea, bronchus, or lung (International Classification of Diseases 162, eighth revision), ie, a total of 76 subjects. Two referents were chosen for each case among deceased workers in the cohort who had not died from cancer of the trachea, bronchus, or lung. The referents were matched to the cases according to year of birth. Altogether the group of cases and referents included 228 subjects.

Source of exposure information
The information on occupational exposure was gathered from company records, which had been kept since the start of operations at the smelter in 1928. The records contained detailed information on the time spent in various workplaces at the smelter by each worker (34).
The assessment of arsenic exposure was based on a safety engineer's estimations of exposure levels in each department during different time periods (19). Exposure to sulfur dioxide (502), which often occurred together with arsenic, was assessed in a similar way. Actual measurements were few however; in 1954 it was reported that the average concentrations of airborne arsenic ranged from 0.06 to 2 mg/m s , while those of 80 2 ranged from 15 to 300 mg/m s at the roasters and copper furnaces and in the converter hall (14). The workers were classified into different categories according to their estimated exposure to arsenic and 802, and the time trend in exposure levels was also taken into account: a. Roaster workers: More than six months of work in the gas purifier or roaster departments. Both arsenic and 80 2 exposure was high for this group.
b. High arsenic: More than six months of work in the arsenic metal, arsenic refining, arsenic salt, building, electric, machine, or selenium departments, excluding roaster workers. The arsenic exposure was high in this group, but lower than for the roaster workers, and the 80 2 exposure was substantially lower than for the roaster workers.
c. High 802: More than six months of work in the anode furnace, converter, copper furnace, or sulfur departments, excluding roaster workers and workers in the high arsenic category. The 80 2 levels were as high in these workplaces as at the roasters, but the arsenic levels were substantially lower.
Arsenic exposure primarily occurred at the workplaces included in the roaster worker, high arsenic, and high 80 2 exposure categories.
Consequently, the workers in these categories were grouped together in the "arsenic exposed" category. The major remaining worksites at the smelter, where subjects in the reference category (no arsenic exposure) had worked, included the battery factory, central laboratory, coal crusher, copper foundry, deliv- a For 11 of the 168 sUbjects reported to be daily smokers for at least 2 a, it was not possible to get data on consumption. b Computed by adding cigarettes (assuming 1 g tobacco/cigarette) and pipe tobacco (calculated from data on weekly consumption).  "A study of chromosomal aberrations in miners exposed to diesel exhausts" I Nordenson, A Sweins, E Dahlgren, L Beckman .
"Felling work, low-back pain and osteoarthritis" E Sairanen, L Brushaber, M Kaskinen "Changes in rat liver microsomal cytochrome P-450 and enzymatic activities after the inhalation of n-hexane, xylene, methyl ethyl ketone and methylchloroform for four weeks" R Toftgard, OG Nilsen, JA Gustafsson .
"A rapid method for the selective analysis of total urinary metabolites of inorganic arsenic" H Norin, M Vahter .
"Distribution and elimination of l·C-styrene in rat" A Carlsson .
"Distribution and elimination of I·C-xylene in rat" A Carlsson .
"Interferences in the spectrophotometric S-diphenylcarbazide determination of environmental hexavalent chromium in a chromium and zinc plating plant" G Carelli, R La Bua, V Rimatori, D Porcelli, A Iannaccone .
Letter to the Editor: "Video computer terminals and occupational dermatitis" V Linden, S Rolfsen .
Letter to the Editor: "A Swedish cancer-environment register available for research" K Wiklund, J Einhorn, G Wennstr6m, E Rapaport .

Volume 7, Number 3, September 1981
"n-Hexane and its toxicologic effects: A review" NK J0rgensen, K-H Cohr 157 "A case-referent study on acute myeloid leukemia, background radiation and exposure to solvents and other agents" U Flodin, L Andersson, C-G Anjou, U-B Palm, 0 Vikrot, 0 Axelson 169 "A cohort study on cancer among workers exposed to an antirust oil" B Jarvholm, B Lavenius 179 "Occurrence of cancer in a small cohort of asbestos-exposed workers" B Hilt, J Rosenberg, S Langc\rd 185 "Topographic and size distribution of asbestos bodies in exposed human lungs" B Gylseth, R Baunan 190 "Age, sleep and irregular workhours: A field study with electroencephalographic recordings, catecholamine excretion and self-ratings" L Torsvall, T Akerstedt, M Gillberg 196 "Testicular function of men occupationally exposed to para-tertiary butyl benzoic acid" "Carbon monoxide criteria: With reference to effects on the heart, central nervous system and fetus" R Rylander, J Vesterlund .

Volume 7, Supplement 3, 1981
"Health hazards and stress factors in small industry -Prevalence study in the province of Uusimaa with special reference to the type of industry and the occupational title as classifications for the description of occupational health problems" T Vihma .

Volume 7, Supplement 4, 1981
"Proceedings of the US-Finnish joint symposium on occupational safety and health and the third annual NIOSH scientific symposium" .

General aspects of occupational health
"Occupational safety and health in the 1980s: Policy options -Historic perspective" HK Abrams , ., .
"Job demands and worker health in machine-paced poultry inspection" B Wil'kes, L Stammerjohn, N Lalich .
"A cross-sectional medical and industrial hygiene survey of workers exposed to carbon disulfide" J Fajen, B Albright, SS Leffingwell .
"Behavioral changes after long-term exposure to organic solvents and their mixtures: Determining factors and research results" K Lindstrom .
"Follow-up studies of workers with bladder neuropathy caused by exposure to dimethylaminopropionitrile" EL Baker, DC Christiani, DH Wegman, M Siroky CA Niles. RG Feldman . "Testing of selected workplace chemicals for teratogenic potential" BD Hardin, GP Bond, MR Sikov. FD Andrew, RP Beliles, RW Niemeier .
"Design considerations in pregnancy outcome studies ot occupational populations" SG Selevan .

Safety
"Risk assessment and the setting of priorities in occupational health and safety" J Rantanen 84 "Epidemiologic principles applied to injury prevention" PJ Coleman