Int Arch Occup Environ Health (2009) 82:851–856 DOI 10.1007/s00420-009-0397-6
O R I G I N A L A R T I CL E
Cancer incidence in the wastewater treatment plant of a large chemical company M. Nasterlack · P. Messerer · D. Pallapies · M. G. Ott · A. Zober
Received: 7 May 2008 / Accepted: 18 January 2009 / Published online: 4 February 2009 © Springer-Verlag 2009
Abstract Objectives To evaluate cancer incidence among employees assigned to BASF’s wastewater treatment plant. Methods We conducted a retrospective cohort study including 477 male employees who had ever worked in the facility for at least 1 year since the start of operations in 1974. Cancers were identiWed by review of occupational medical records and a standardized questionnaire completed by the participants or their next of kin. ConWrmation through hospital records was sought for all reported cases after obtaining informed consent. Standardized incidence ratios (SIR) and 95% conWdence intervals (CI) were computed using comparison data provided by the Saarland Cancer Registry. Further comparisons were made between three diVerent subgroups of employees, working in maintenance, wastewater processing, and sewage sludge treatment. Results A total of 50 cancers were observed (SIR 1.14, CI 0.85–1.51). Colorectal (1.14, 0.42–2.48), bronchial (1.40, 0.67–2.57) and prostate (1.15, 0.42–2.50) were the most frequently observed cancers. Five cases of bladder cancer were found in the total cohort (1.75, 0.57–4.09), with four of them occurring in the sewage sludge treatment area (6.82, 1.86–17.46). Allowing for a 10-year lag did not signiWcantly change the results. Conclusions The overall cancer experience among employees of the wastewater treatment plant was similar to M. Nasterlack (&) · P. Messerer · D. Pallapies · A. Zober Occupational Medicine and Health Protection, GUA/C, H 306 BASF SE, 67056 Ludwigshafen, Germany e-mail:
[email protected] M. G. Ott Medical Department, BASF Corporation, 100 Campus Drive, Florham Park, NJ 07932, USA
that of the corresponding general population. The Wnding of an excess risk for bladder cancer in one subgroup of workers was unexpected with regard to the available literature. There is no straightforward explanation for this Wnding, and it may be due to chance. An extended follow-up of this cohort will take place after 5 years. Annual bladder cancer screening is oVered to active and retired employees from this plant for the time being. The current working conditions and work practices have been re-assessed by occupational hygienists and deemed to be safe. Keywords Bladder cancer · Cohort study · Wastewater treatment plant
Introduction Sewage water contains a complex mixture of pathogens and toxins, including potential mutagens and carcinogens (Scarlett-Kranz et al. 1986). Wastewater workers may be exposed to such agents mainly through inhalation of gases or aerosols and through dermal contact. In the further process of wastewater treatment, handling and incineration of the sewage sludge may lead to additional possibilities of exposure. Studies on long-term health outcomes of working in wastewater treatment plants, namely on cancer incidence and mortality, have rarely been conducted in the past, possibly owing to comparatively small numbers of workers usually involved. Results have been inconsistent across studies, with mostly small increases in all-cancer incidence or mortality reported, but with no consistent pattern with respect to diVerent target organs or anatomical sites (Thorn and Kerekes 2001). We conducted the present study in response to concerns raised by employees of BASF’s wastewater treatment plant at Ludwigshafen, Germany,
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after two active employees (maintainance workers, 43 and 47 years old) died from cancer (stomach and lung) at the beginning of 2004. This plant serves the world’s largest chemical site with more than 200 production plants and currently some 33,000 employees, and also treats the eZuents from three of the neighbouring communities with about 200,000 inhabitants. The study was descriptive in nature and designed to assess whether or not the overall cancer experience of waste water treatment employees was comparable to that expected for the corresponding general German population.
Methods We conducted a retrospective cohort study on cancer incidence. The study group consisted of 477 male employees assigned to the Ludwigshafen wastewater treatment plant for at least 1 year since the start-up of the facility in 1974. Few women (n = 7) were employed in the plant during this time period, and no cancers had occurred among them. Cancers were identiWed by review of occupational medical records for all employees during the time of their active employment, and additionally by a 2005 mailed questionnaire to employees no longer working at the site or for whom recent information was not available. Information regarding 46 deceased persons was gathered through responses by next-of-kin, where possible. The questions pertained to ever having experienced cancer, family history of cancer, job history, and history of smoking. For each reported cancer case, veriWcation was sought through hospital discharge letters and histological reports, which were obtained after informed written consent. Thus, all reported cancers could be conWrmed using independent sources. Individual job history was assessed using questionnaire responses as well as plant employment records. Employees were subcategorized into those assigned to wastewater processing (n = 124), sewage sludge treatment and incineration (n = 199) or maintenance (n = 154) jobs. The expected number of cancer cases was calculated using 5-year age group and calendar year-speciWc (1974–2005) comparison data for the general male population provided by the Saarland Cancer Registry (http://www.krebsregister.saarland. de). Person years of observation were accumulated from date of Wrst assignment in the plant to date of latest available information on health status or up to December 31, 2005. Person years, standardized incidence ratios (SIR) and conWdence intervals (CI) were calculated using the statistical program PAMCOMP (Taeger et al. 2000). SIRs were calculated both for the whole study period and after allowing for a 10-year lag since Wrst employment in the plant. All employees, as well as the management and workers’ council had been informed in advance during several
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workshops about the purpose and methods of the study before starting the investigation; all stakeholders formally endorsed the concept. Participation was entirely voluntary and could be declined without providing a reason. All study results have been communicated to and extensively discussed with the stakeholders mentioned above.
Results Vital status was ascertained for all but 21 (4.4%) of the 477 eligible men. No questionnaires were sent to 29 individuals for whom current addresses were unavailable. We received a total of 373 responses to the 438 questionnaires mailed out, resulting in a participation rate of 85.2%. Thirty of 244 active employees (12%) failed to return a completed questionnaire. Causes for non-response in general included refusals (n = 10), living abroad (n = 4), deceased (n = 4), and simply not responding to the letter. Selected characteristics of the study cohort are summarized in Table 1. With respect to cigarette smoking 31% were “never-smokers”, 65% “ever-smokers”, and in 4% there was no information on smoking status provided. The mean age at the end of follow-up was 51.3 years in the total group (SD 13.0, range 19–83 years). The 124 men
Table 1 Selected characteristics of wastewater treatment group Characteristic
Total group (n = 477) No.
%
Birth year 1922–1939
98
21
1940–1949
105
22
1950–1969
226
47
48
10
1970+ Vital Status through 2005 Alive
410
86
Deceased
46
10
Unknown
21
4
Cigarette smoking Never smoked
147
31
Ever smoked
310
65
20
4
Unknown
Year started work in waste water treatment plant 1974–1979
200
42
1980–1989
131
27
1990+
146
31
Maintenance
154
32
Waste water
124
26
Sewage sludge
199
42
Work area
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assigned to wastewater processing (mean age 54.0) contributed 2,357 person years, the 199 men working in the sewage sludge treatment and incineration (mean age 50.7) contributed 3,782 person years, and the 154 maintenance employees (mean age 47.6) contributed 3,178 person years of follow-up. The average length of follow-up per person was 19.5 years. An overview of the cancers observed, as well as a breakdown of Wndings across the diVerent occupational categories, is provided in Table 2. A total of 50 cancers including 5 non-melanoma skin cancers were observed, with 43.8 cases expected (SIR 1.14, 95% CI: 0.85–1.51). The most frequently observed cancer types were bronchial (n = 10), colorectal (n = 6), prostate (n = 6), urinary bladder (n = 5), and non-melanoma skin cancer (n = 5). Analysis by occupational category yielded a small, albeit statistically non-signiWcant, excess of lung cancer in all three groups of workers. A similar non-signiWcant excess of non-melanoma skin cancer and cancers of colon/sigmoid/rectum was found in the group of sewage sludge treatment workers, accompanied by a respective deWcit of these cancers in the other two groups. Four of the Wve bladder cancers occurred in sewage sludge treatment workers (SIR 6.82, 95% CI: 1.86-17.46). Allowing for a 10-year lag since Wrst employment in this plant resulted in a loss of nine cancers (two prostate, one thyroid, one pancreas, two oral cavity, two NHL, one lung), with little eVect on the resulting risk estimates for all cancers (SIR 1.32,
95% CI: 0.94–1.78). However, all Wve bladder cancers remained in the data set (SIR 2.04, 95% CI: 0.66–4.76). Details of the Wve bladder cancer cases are reported in Table 3. Age at diagnosis varied between 56 and 72 years, and the latency period between Wrst employment in the plant and date of diagnosis was 18–27 years. Only one of the Wve persons was a “never smoker”. Among the four cases of bladder cancers in the sewage sludge treatment area, there were three in workers who had been active in the plant since start-up. The fourth person who had entered the plant 6 years later had a conWrmed previous exposure to established occupational bladder carcinogens; namely aromatic amines. There was no indication from their personal work history for occupational exposure to known or suspected bladder carcinogens for any of the other cases. But even if this one case is eliminated, the observation of three additional bladder cancers in the group of sewage sludge treatment workers remains statistically signiWcant (SIR 5.1, 1.1– 14.9). On other hand, arguably, one case of renal pelvis cancer may be additionally counted into this category, because of the histological identity, albeit in a diVerent location, and possibly shared causality with the bladder cancers. The person aVected had been a consulting engineer in the sewage sludge incineration plant for approximately 5 years after 1977. His age at diagnosis was 60 years, 25 years after his Wrst employment there. He had been a smoker of 6–8 cigarettes per day since age 15.
Table 2 Incident cancers in employees of the wastewater treatment plant, and for the subgroups working in maintenance, wastewater processing, and sewage sludge treatment (subgroup SIR and conWdence intervals for cancers n > 4 in the total cohort) ICD 10
Total cohort n (SIR, 95% CI)
Maintenance n (SIR, 95% CI)
Oral cavity, Pharynx (C01-C10)
3 (0.99, 0.20–2.89)
1
Stomach (C16)
3 (1.87, 0.38–5.46)
2
1
Colon/sigmoid/rectum (C18-C20)
6 (1.14, 0.42–2.48)
1 (0.75, 0.02–4.18)
1 (0.55, 0.01–3.08)
4 (1.89, 0.51–4.83)
Pancreas (C25)
2 (2.42, 0.29–8.76)
1
1
Bronchus/lung (C34)
10 (1.40, 0.67–2.57)
3 (1.68, 0.34–4.92)
Non-melanoma skin (C44)
5 (0.90, 0.29–2.11)
1 (0.70, 0.02–3.91)
Soft tissue (C49)
1 (30.77, 0.78–171.44)
1
Prostate (C61)
6 (1.15, 0.42–2.50)
2 (1.55, 0.19–5.58)
Testis (C62)
1 (0.98, 0.02–5.48)
Kidney (C64)
1 (0.70, 0.02–3.91)
Renal pelvis (C65)
1 (15.34, 0.39–85.45)
Wastewater n (SIR, 95% CI)
Sewage sludge n (SIR, 95% CI) 2
3 (1.21, 0.24–3.53)
4 (1.38, 0.38–3.55) 4 (1.77, 0.48–4.55)
2 (1.06, 0.13–3.83)
2 (0.98, 0.12–3.54) 1
1 1
Urinary bladder (C67)
5 (1.75, 0.57–4.09)
Thyroid gland (C73)
1 (3.74, 0.09–20.81)
1
1 (1.00, 0.03–5.55)
UnspeciWed (C80)
1 (0.95, 0.02–5.28)
1
Hodgkin’s lymphoma (C81)
2 (6.69, 0.81–24.17)
1
Non-Hodgkin’s lymphoma (C82)
1 (0.89, 0.02–4.95)
Myeloid leukaemia (C92)
1 (2.33, 0.06–13.00)
All cancers
50 (1.14, 0.85–1.51)
4 (6.82, 1.86–17.46)
1 1 1
14 (1.22, 0.67–2.05)
12 (0.82, 0.42 - 1.44)
24 (1.39, 0.89–2.07)
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1979 5/day, 1982 Ex-smoker
No known history of occupational exposure to bladder carcinogens
Wastewater processing
Documented smoking history (as far as available)
Occupational exposure history
Occupational category
Sewage sludge treatment
No known history of occupational exposure to bladder carcinogens
1973 18/day, 1977 5/day, 1993 Ex-smoker
Multifocal urothelial carcinoma (pT1 pN0 M0 G3)
56
1992
1974
1966
1936
Case 2
Sewage sludge treatment
History of accidental exposure to aromatic amines, case acknowledged and compensated as occupational disease
20–30 cigarettes per day over 50 years
Urothelial carcinoma (pTa G1)
62
2002
1980
1966
1939
Case 3
Sewage sludge treatment
No known history of occupational exposure to bladder carcinogens
No known history of occupational exposure to bladder carcinogens
Sewage sludge treatment
Non-smoker
Urothelial carcinoma (pTa G2)
57
2000
1974
1957
1942
Case 5
15–20 cigarettes per day over 35 years
Multifocal urothelial carcinoma (pT1 G2–3) and CIS (trigonum B)
72
2001
1974
1974
1929
Case 4
CIS carcinoma in situ, histological classiWcation and grading according to TNM; 1979 5/day = 5 cigarettes per day as an information provided in 1979
64
Year of diagnosis
Papillary urothelial dysplasia, CIS (pTis)
1997
Worked in sewage plant since
Histological diagnosis (as provided in the hospital records)
1974
Year of hire in BASF
Age at diagnosis
1933
1954
Year of birth
Case 1
Table 3 Characteristics of the Wve cases of bladder cancer
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Discussion The overall cancer incidence in this small cohort of wastewater treatment plant workers was not signiWcantly diVerent from that of the general population in the neighbouring region. The observed SIR of 1.14 for “all cancers” is similar to what has been reported from the few available studies of comparably exposed populations (Thorn and Kerekes 2001). In a cohort of 487, white male sewage authority workers LaXeur and Vena (1991) found a standardized mortality ratio (SMR) for all cancers of 1.19 (95% CI: 0.79–1.7), and statistically signiWcantly elevated SMR for larynx (7.93, 1.59–23.96) and liver cancer (5.4, 1.10– 16.05). Betemps et al. (1994) reported the proportionate mortality ratio (PMR) for “all malignant neoplasms” from a cohort of 3,175 workers in a water reclamation plant to be 1.00 (0.89–1.12), with non-signiWcantly elevated PMR for the subcategories of esophagus (1.58, 0.80–3.13), stomach (1.47, 0.89–2.42) and prostate cancer (1.30, 0.87–1.94) as well as leukemia (1.37, 0.76–2.46). Friis et al. (1993) in a cohort of 656 male sewage workers found the SMR for “all cancers” close to unity (1.02, 0.72–1.38), a borderline signiWcantly elevated SMR for stomach cancer (2.73, 1.00– 5.94) and non-signiWcantly elevated SMR for brain, kidney and lung cancer. In the extended follow-up of this cohort (Friis et al. 1999) the SIRs were reported as follows: “all cancer” (1.2, 0.9–1.5), prostate cancer (1.6, 1.0–2.5), cancer of the nose and nasal sinuses (12, 1.5–44, based on two cases), and stomach cancer (2.3, 0.99–4.5). Hansen et al. (2003) compared the mortality of 591 wastewater workers to that of 1,545 water supply workers. These investigators reported elevated relative risks (RR) for “all cancer” mortality (1.34, 0.95–1.89) and incidence (1.27, 0.97– 1.67), with signiWcant excesses in the incidence of respiratory (1.65, 1.00–2.74) and primary liver cancers (8.9, 1.5– 51.5). The comparison of the wastewater workers to the Danish general population yielded an “all cancer” SIR of 1.50 (1.17–1.90), with elevated SIR for respiratory (2.09, 1.27–3.22), digestive (1.34, 0.73–2.25) and primary liver cancer (5.26, 1.43–13.48). Wild et al. (2006) in a cohort study in 1,722 sewage workers, found an elevated SMR for “all cancers” (1.37, 1.20–1.56), where namely “upper digestive tract” (1.54, 1.15–2.02), liver (1.85, 1.06–3.00) and lung (1.47, 1.14–1.86) contributed signiWcantly elevated rates. Taken together, the organs and sites found mostly aVected by cancer in the studies reported here appear to be of no particular relevance in our study population. On other hand, our Wnding of an elevated rate of bladder cancer speciWcally in the subgroup of sewage sludge treatment workers appears to have little support in the available literature. Two studies reported modest deWcits, but based on small numbers (Friis et al. 1999; Wild et al. 2006), two
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studies did not report on bladder cancer (Betemps et al. 1994, Hansen et al. 2003), and one study reported 2 observed versus 0.9 expected cases (LaXeur and Vena 1991). Bladder cancer is among the most frequent cancers in males and has been extensively studied in case-control studies (Kogevinas et al. 2003; Myslak and Bolt 1988). However, we are aware of only one case-control study that mentioned sewage work as an occupational risk factor for bladder cancer (Sorahan et al. 1998). Established risk factors for bladder cancer are extensive use of phenacetin-containing analgesics, chronic schistosomiasis, arsenic in drinking water, cigarette smoking, and certain aromatic amines (Bichler and Harzmann 1984; Cohen et al. 2000). While the former three factors do not provide a plausible explanation for the observed bladder cancers in the present context, the latter two factors merit further discussion. Carcinogenic aromatic amines have been produced and handled at the BASF site in the past (Nasterlack et al. 2001), and it cannot be excluded retrospectively that they also reached the wastewater stream. Employees have indicated that occasional dermal contact with wastewater or sewage sludge may have occurred in the past, thus providing a possible route of exposure. In this case, however, the potential for exposure to these amines should be at least as high, if not higher, in workers employed in wastewater processing. Although some important carcinogenic aromatic amines like beta-naphthylamine and 4-aminobiphenyl are not eliminated to a notable extent in the wastewater puriWcation process, they are also not expected to concentrate in the sewage sludge. Smoking habits did not diVer appreciably between the three occupational subgroups. Approximately 30% of our study population self-reported having been never-smokers, which is comparable to census data from the general male population (Robert Koch Institut 2006). There is thus no indication that diVerences in smoking patterns between our study population and the general population could explain the bladder cancer excess found in this study. DiVerences in socio-economic status between both populations cannot fully be excluded, but detailed information on this point is lacking for the control population and the direction of a possible resulting bias cannot easily be determined. For the time being, there is too little information available to decide whether our Wnding of an elevated bladder cancer risk in one subgroup of workers represents an eVect of an up to now unidentiWed occupational exposure or merely a chance Wnding. Given the expected long latency period for the development of bladder cancer after exposure to carcinogens, a continued excess of bladder cancers would be expected in our cohort even if the causal exposure has ceased to exist in the meantime. The further development of the incidence Wgures will shed more light on this question. In the context of the respective German law there
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is presently no basis for these cases to be acknowledged as occupational diseases. The employees have been informed about this situation and it was concluded to aim at an extended follow-up of the cohort after 5 years time. In the meantime, annual bladder cancer screening is oVered to all present or former employees who ever worked in this plant for more than 1 year, irrespective of current employment status. There was consent among occupational hygienists and employees’ representatives that the current work practices suYciently prevent unintentional contact with sewage water or sludge.
Conclusion The overall cancer experience among employees of the wastewater treatment plant was similar to that of the general population. The Wnding of an excess risk for bladder cancer in the subgroup of sewage sludge treatment workers was unexpected and is without precedent in the available literature. There is no straightforward explanation for this Wnding for the time being, and it may be due to chance. An extended follow-up of this cohort will take place after 5 years to help to clarify this important question. The current working conditions and work practices have been reassessed by occupational hygienists and deemed to be safe. Acknowledgment We thank the workers of the wastewater treatment plant, their representatives, and the responsible management for their co-operation and support. The authors are employees of BASF SE, Germany, which operates the plant. The authors declare that they have no other competing interests.
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