cancer incidence and mortality of isocyanate exposed workers from the swedish polyurethane foam industry: updated findings 1959–98
Methods: mortality and cancer incidence (1959–98)
The experience of 4175 male and female employees employed in one of the nine Swedish polyurethane foaming plants for a period of 1959-87 was investigated.
Comparison based on calendar year, gender and V.
Mortality and incidence of specific age groups in Sweden.
Exposure to toluene diammonium in the workplace and tasks (TDI)
Diammonium hexyl (MDI)
Occupational health specialist
Results: fewer cancer cases were observed than expected, but the incidence of lung cancer in women increased.
However, the incidence of lung cancer in women with \"obvious exposure\" TDI or MDI is not higher than in women with \"no or low exposure.
In addition, a nested case reference study did not find that polyurethane dust exposure was more common in female lung cancer cases than in reference cases.
No increase in mortality was observed in the cohort for chronic blocked lung disease.
Conclusions: The results support the results of two other cohort studies, namely, increased risk of lung cancer among female workers in polyurethane foam manufacturing.
The chances or confounders of smoking do not clearly explain the coherent findings.
However, this study failed to link the work of exposure to isocyanate to the risk of lung cancer.
Methods polyurethane foam was manufactured by Swedish factory and chemical Expo, in which TDI or MDI was used to produce flexible foam blocks or dead mold materials.
From 1958 to 1974, the time for manufacturing started varies.
Table 1 gives the exposure time of TDI and MDI for each plant.
View this table: View the inline View pop-up table 1 TDI and MDI exposure period and queue size and personnel-
The time-weighted average concentration of TDI in the air of the year observed by workers employed for at least one year is generally less than 100 μg/m3 from the first sampling in 1965, below 20 μg/m3 at the end of 1980 seconds.
The corresponding value of MDI is less than 10 μg/m3.
Much higher value (
TDI up to 3 mg/m3; MDI up to 0. 35 mg/m3)
However, it has been measured repeatedly.
In addition, it is reported that many accidents were exposed to isbluate due to spills and leaks.
As a result, as of 1998, there were only five factories operating.
After 1990 TDI, TDI was used in only three factories.
Since the vapor pressure of MDI is much lower, the use of MDI instead of TDI reduces the emission of isoester.
Exposure levels have declined over the years.
In a large survey conducted by our department in 2000-01 on air exposure to isoocyan salts in 13 factories in the Swedish polyurethane industry, 113 workers monitored were exposed to total diisoester with a range of 0. 01–52 (median 4)μg/m3 (
Personal communication CJ Sennbro).
Workers may also be exposed to other chemicals, such as bis (2-
For methyl amine groups)
Ether, dimethyl chlorhexamine, dimethanol Amine, ethanol, methyl ketone-o-chloroaniline (MOCA), N-
Trimethamine, trimethamine and trimethamine (DABCO)
Organic solvents such as petroleum, methyl chloride, methyl ethyl ketone, styrene, vinyl chloride, methane, toluene, and liquor.
However, these other chemicals are rarely monitored.
A more detailed description is given in the previous publication.
CohortName, date of birth, address, date of commencement and end of employment and workplace or work tasks were obtained through company records.
Workers who leave or die the year before the completion of the company\'s registration are not included in the queue.
70 subjects with a personal identification code that cannot be retrieved and 686 subjects with missing data at the start or end of employment must be excluded.
From 1958 to 1987, the remaining 6426 workers were employed for at least one day.
The last group was limited to 4175 workers employed for at least one year (table 1).
All of these subjects, except 139, have information about the workplace or the task of work.
The results do not indicate that TDI and MDI are human carcinogens.
So far, the risk of lung cancer in women has continued to increase, which requires future tracking of employees in the polyurethane foam industry.
The beginning of the observation period is defined as the first calendar year of the beginning of the bubble, and the company record is considered complete and valid.
From 1958 to 1975, the situation varies in nine factories.
The median date of birth calendar year for queue members is 1951 (Range 1896-1972)
The median contact for the first year was 1978 (range 1958–86)
The median follow-up period was 19. 2 years (range 0. 3–40).
The study was approved by the ethics committee of Lund University.
Exposure estimates and work tasks for the 9 factories seach workplace and work tasks by an experienced occupational health practitioner made a clear \"no exposure\" for each calendar year as of 1987 low or intermittent exposure \", or \"obvious exposure\" of TDI or MDI \".
\"Apparent exposure\" classification refers to direct exposure during foaming or molding or when working in the same place.
The \"low or intermittent exposure\" classification refers to the treatment of cured materials near places used for foaming or molding, or the treatment of only intermittent exposure.
Potential exposure after 1987 must be ignored, as some plants have been closed since the last analysis of the current cohort, leaving no effective retrospective exposure classification for a period of time after 1987.
Of the 3988 queue members, 4175 can classify all working hours based on exposure to TDI or MDI.
Of the contact classification workers, 1394 were constantly experiencing no, low or intermittent contact with TDI or MDI, and 1679 were constantly experiencing significant contact.
The remaining 915 subjects had different exposures during their employment. The exposure-
Over time, response calculations were limited to 3073 subjects with stable exposure classification.
There is a gender difference in the work tasks of the factory.
Compared with 12% of male workers, female workers participated in the finishing of foam products.
These work tasks include grinding, punching, sawing and cutting, which can lead to exposure of polyurethane dust.
Unfortunately, no dust measurements were made at the factory.
Information and risk estimation information on causes of death and tumors for the period 1959-98, coded according to the International Classification of Diseases (ICD)
Eight revisions from the Swedish Bureau of Statistics.
Information on malignant tumors during the 1959-98 period coded under ICD\'s seventh revision was obtained from the Swedish Cancer Registry.
Information was obtained from the Swedish population registry on important status and date of migration.
In December 31, 1998, 337 of the 4175 workers died, 123 immigrated, and the rest remained alive, living in Sweden.
No one has lost follow-up.
Use reason, calendar year, gender and V-through SYDCAP queue items-
Annual rate for specific age groups.
These ratios are calculated based on the incidence of specific causes of death, malignant tumors, and population counts obtained by the Swedish Bureau of Statistics and the Swedish Cancer Registry.
The date of death, the date of immigration or an 80-year-old birthday of a person is used as a personal end point, whichever comes first.
A total of 83 023 people
Year of risk (table 1).
95% confidence intervals (95% CIs)
Standardized mortality and morbidity for specific reasons (SMRs and SIRs)
Calculated by treating the observed number as a Poisson variable, or if the observed value is greater than 15, treat it as a normal variable.
The term significant indicates that 95% CI does not include 1. 00. Nested case-
For each of the 12 female lung cancer cases, a reference study was performed, and 3 reference women were randomly selected from a cohort without cancer, but matched with the calendar year of birth.
2 Occupational health teachers (HT, HW)
Using available information about each topic in the factory and workplace or work task, a rough classification of the likelihood that these topics will be heavily exposed to polyurethane dust.
Due to the lack of exposure data, one of the cases could not be classified.
The ratio and 95% CIs were calculated using conditional logistic regression.
Results a total of 337 workers died during the observation, much less than expected (SMR 0. 84, 95% CI 0. 75 to 0. 93, table 2).
There is no increase in mortality from malignant tumors or chronic lung disease.
However, an increase in lung cancer mortality was observed only in women (SMR 3. 52, 95% CI 1. 69 to 6. 48).
View this table: 1958 and 9 cases of cancer events were observed for at least one year, with a mortality rate of-99 (SIR 0. 87, 95% CI 0. 75 to 0. 99, table 3).
Increased incidence of lung cancer in women (SIR 3. 00, 95% CI 1. 55 to 5. 24)
But not in men.
Seven of the 12 women with lung cancer were also registered as dying from the disease, while two died from concurrent diseases and three were still alive.
View this table: genderA was observed to have a cancer incidence of 1959-98 in subjects with an increase in the number of brain and nervous system malignant tumors for at least one year (SIR 1. 49, 95% CI 0. 83 to 2. 46)
There seems to be no difference between men and women.
Incidence of rectal cancer, non-
There was no increase in lymphoma and pancreatic cancer.
The overall incidence of cancer has not increased, even after falling behind in the first 20 years after the onset of exposure, but the SIR of malignant tumors in the brain and nervous system has increased (2. 45, 95% CI 0. 90 to 5. 33, table 4).
View this table: View inline View pop-up table 4 out of 1959 subjects employed for at least one year, cancer incidence is 4175-98 and there is no one after at least 20 years since the first exposure
Association of TDI or MDI exposure levels or lengths with response between total cancer incidence, brain cancer, or female lung cancer (table 5).
View this table: View the inline View popupTable 5 exposure to TDI or MDI and cancer incidence in workers in the polyurethane foam industry, these workers were exposed to classified stable female lung cancer cases during their work period more generally than in the references (table 6).
View this table: looking at the association between the inline View popupTable 6 Nested Case Reference Study exposure to polyurethane dust and the incidence of lung cancer in women discussion the main outcome of this study is the increased incidence of lung cancer among female workers in polyurethane foam manufacturing, this is notable because it has also been observed in the UK and the US.
A significant increase in lung cancer mortality (SMR 1. 81, 95% CI 1. 26 to 2. 51)
In the queue in the UK, 5 female workers were seen, and in cohor6 in the US, none
A significant increase in lung cancer mortality among female workers (SMR 1. 73, 95% CI 0. 75 to 3. 41).
The reason for this consistent pattern of increased risk of lung cancer in women is not obvious.
In Study 5 in the UK and in the current study, both attempts were made to assess exposure-
The response associated with the estimated exposure to TDI or MDI was not found.
No dose was attempted in the US study-
Insufficient dose 6-
Reaction associations in the UK study and in this study may oppose the causal effect of isocyanate exposure.
On the other hand, the exposure levels of TDI and MDI vary greatly in different workplace and interior of the plant.
The information obtained from the company records about the subject\'s workplace and work tasks in the cohort is not always specific, at least not in the Swedish cohort.
To sum up, this may lead to
Different classification errors of exposure, which will reduce the possibility of association of excess risk with specific exposure.
In addition, the current exposure
Response Analysis based only on 11 lung cancer cases has a lower statistical ability to detect very high risk increases associated with high exposure levels.
The manufacture of polyurethane foam includes not only exposure to isbluate, but also exposure to many other chemicals, which unfortunately are rarely monitored such as expansion agents, lubricants, accelerators and
The use of these compounds varies between the plants involved in this study, so exposure to islanate is the only common chemical feature of the plant.
In the first report of the UK study, an attempt was made to assess the risk of lung cancer in women associated with other types of chemicals through Nested Case Reference analysis.
1 No obvious patterns were seen, but the statistical capacity was low due to the small number of cases and references.
More work tasks among female workers may result in air exposure to polyurethane dust compared to male workers.
However, the reference analysis in this study did not support exposure to polyurethane dust as a risk factor for lung cancer in women.
However, it should be emphasized that dust measurements are rarely carried out in the plant and therefore only a rough assessment of exposure can be made.
This, coupled with the small size of the study, limits the possibility of assessing a very close association between polyurethane dust and lung cancer.
Unfortunately, there is no information about smoking habits in the UK, US, 6 or current cohort.
However, there is indirect evidence that smoking is unlikely to explain the excessive risk of lung cancer in women.
First, no increase in lung cancer in men was observed in the three cohort (
UK queue: SMR 1. 07;
US queue: SMR 0. 79;
The current research object: Mr. 0. 40).
Therefore, if smoking leads to an increased risk of lung cancer for female workers, we must assume that there are very different smoking habits between male and female workers.
Second, smoking is a risk factor for cardiovascular death, but the corresponding SMRs for women did not increase in the three queues (UK cohort: 1. 09; US cohort: 0. 73;
This study: 0. 52).
Due to the protective effect of endogenous estrogen, age-related cardiovascular mortality increased later in women than in men.
Low SMR in women with cardiovascular disease in this cohort was not the result of a cohort that was still too young, as SMR in the age group 70 and older was 0. 55.
No increase in mortality from respiratory diseases was observed in this study or in the US study, or more specifically in chronic blocked lung disease.
6 in the UK study, female workers had a significant trend towards non-female SMRs
In the past decade, malignant respiratory diseases have been increasing.
5 However, no association was observed with ocyan acid salt exposed to the job.
Therefore, there is no convincing evidence that exposure to ocyan acid salt in the polyurethane foam manufacturing industry can lead to an increase in the mortality rate of patients with obstruction lung disease.
In conclusion, the results of this study support the results of two additional cohort studies, namely, increased risk of lung cancer among female workers in polyurethane foam manufacturing.
However, there is no dose
Reaction associations of TDI or MDI occupational exposure were observed.
However, it is important to note the inherent limitations of retrospective exposure assessment.
The accidental discovery or confusion of smoking is not a clear explanation of the risk of excessive smoking.
Occupational risk factors cannot be ruled out yet, and long-term follow-up of a more in-depth exposure analysis for all three groups helps to better understand the observations.
The work was funded by AFA.
Medical school of insurance, Lund University, the Skane area, and Lund University Hospital.
International Agency for Cancer Research.
IARC monograph on assessing the risk of chemicals to human cancer. Re-
Evaluation of some organic chemicals. Vol 71.
Lyon: IARC, 1999.
PGJ, art JHE, Lomax LG, etc.
Study on chronic inhalation toxicity and carcinogens of inhaled polymerization of diammonium (polymeric MDI)
Aerosol on mice
Fundam Appl Toxicol1994; 22:195–210.
Science stemkl mer KL, Binham E, Barkley W.
Lung reaction of polyurethane dust.
Outlook for Environmental Health11:109–13.
Pope D. Sorahan T.
Mortality and cancer incidence of workers in the UK flexible polyurethane foam industry.
Br J Ind Med1993; 50:528–36.
Scientific OpenUrlPubMedWeb sorsorahan T, Nichols L.
Mortality and cancer incidence among workers produced in the UK flexible polyurethane foam industry: Latest findings, 1958-98.
Occup Environment 2; 59:751–8.
OpenUrlAbstract/free full text schnorr TM, Steenland K, Egeland GM, etc.
Mortality of workers exposed to toluene diammonium in polyurethane foam industry.
Occupational Medical environment Med1996; 53:703–7.
OpenUrlAbstract/free full Text ↵ Hagmar L, Welinder H, Mikoczy Z.
Cancer incidence and mortality among polyurethane foam manufacturing workers.
Br J Ind Med1993; 50:537–43.
Scientific OpenUrlPubMedWeb haghagmar L, Strömberg U, Welinder H, et al.
Incidence of cancer and exposure to toluene Diester and submethyl Diester: a cohort-based case reference study in the polyurethane foam manufacturing industry.
Br J Ind Med1993; 50:1003–7.
X Marek WA of OpenUrlPubMedWeb Science limbaur, J of the ammonites, etc.
Breathing and other hazards of Ocyan salt.
Environmental health 19 94; 66:141–52.