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Administrative data

Endpoint:
epidemiological data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
A 17-year epidemiological study on changes in lung function in toluene diisocyanate foam workers
Author:
Clark RL, Bugler J, Paddle GM, Chamberlain JD, Allport DC
Year:
2003
Bibliographic source:
Int. Arch. Occup. Environ. Health.;76: 295-301

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
other: lung function
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
17-year epidemiological study on changes in lung function due to occupational exposure to TDI

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
In an earlier study, a population of workers from 12 UK factories was studied between 1981 and 1986. A survivor cohort of 251, of whom 217 were in the 1981–1986 study, was examined again in 1997–1998. Modified British Medical Research Council respiratory questionnaires and lung function measurements were completed for each of the 251 subjects at the beginning and end of the 17-year study period. Mean TDI exposures for all jobs in which subjects were employed were assessed and related to their occupational histories.

HYPOTHESIS TESTED
To determine whether longitudinal declines in ventilatory capacity and the occurrence of respiratory symptoms in workers manufacturing polyurethane foam were related to toluene diisocyanate (TDI) exposure.

METHOD OF DATA COLLECTION
- Questionnaires: The 1976 version of the Medical Research Council Respiratory Questionnaire for Chronic Bronchitis was completed for each participant at the time of entry into the study and between May 1997 and May 1998. This questionnaire was used to ensure comparability with that used in the earlier study. Height and weight were also measured.
- Job history records: Job histories from the date of the first lung function test were obtained by the interviewing of the 251 subjects. Approximately 100 job categories were defined at the time of the initial survey; these covered all exposed, handling and low-exposure jobs being undertaken by the study participants. Each job was assigned an estimated isocyanate exposure in each year, from which a mean daily level of exposure was calculated for each subject between the first and the last lung function measurement.
- Pulmonary function testing: The earliest measurement of pulmonary function during the period 1981 to 1986 was used as the first lung function value in this study. This, together with a further measurement in 1997/ 1998, provided the lung function data. Maximum expiratory flow–volume curves were recorded by a McDermott bellows spirometer, which was calibrated daily and tested for volume and timing errors at intervals during the day. The same spirometer was used throughout, and all measurements for both the study in 1981 to 1986 and the follow-up in 1997 to 1998 were made by a single observer. The mean of the three highest FEV1 values from five technically satisfactory flow–volume curves, together with the mean FVC and peak flow calculated from the same expirations, were used for the statistical analysis.

STUDY PERIOD: 1981-1998
Exposure assessment:
estimated
Details on exposure:
TYPE OF EXPOSURE: occupational

EXPOSURE PERIOD: 17 years (1981 - 1998)

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:
Subjects were placed into one of three groups depending on their job at the time they first joined the study. The three groups were defined as follows:
1. An exposed group, which was employed in the manufacture of polyurethane foam or was handling freshly manufactured products.
2. A handling group of workers handling cold (previously manufactured) polyurethane products.
3. A low-exposure group of shop-floor and office workers who were employed on the manufacturing sites, but were not directly involved in polyurethane manufacture, and who may have had at most some minimal background exposure due to the use of TDI elsewhere in the factories.

TYPE OF EXPOSURE MEASUREMENT:
During the earlier study (1981 to 1986), 2294 valid personal TDI measurements were made with continuous paper tape monitors (MCM type 4000). These instruments have been recognised as being reliable in the determination of TDI vapour concentrations. The monitors were worn on the chest and measured breathing-zone concentrations of TDI over the work shift. Identical monitors capable of measuring TDI in concentrations between 1 and 40 ppb at an airflow rate of 200 ml/min continued to be used at participating factories throughout the period 1987 to 1998. During this period, sampling was undertaken and paid for by the companies themselves. In consequence, all samples were taken in production areas (exposed group subjects) with none being collected for handling or low exposure jobs. In total, 1039 such samples were taken between 1987 and 1998.

EXPOSURE LEVELS:
Of the 1039 personal measurements of TDI exposure, 1004 allowed valid calculations of daily cumulative exposure to be made. The range of these results was as follows:
• 1–5 ppbh, n=263
• 5–10 ppbh, n=418
• 10–20 ppbh, n=219
• 20–40 ppbh, n=91
• 40 ppbh, n=13
This suggests that some 1.3% (13 out of 1004 results) were in excess of the current UK maximum exposure limit of 46.4 ppbh (equivalent to 0.02 mg NCO/m3).
The 1004 measurements were used together with the 2294 measurements made between 1981 and 1986 to calculate an average daily dose for each exposed job at each participating factory.
Statistical methods:
Analysis of annual loss rates of lung function variables was made by multiple linear regressions using the STATGRAPHICS computer package. All the explanatory variables listed below were included in the regressions initially. Variables not significant at the 10% level were then rejected one by one.
The dependent lung function variables, which were adjusted for height and for the continued physical growth of those less than 23.5 years of age, were:
• FEV1: The volume in litres expired during 1 s starting immediately after expiration of the first 100 ml from full inspiration.
• FVC: The total volume in litres from full inspiration
• PEAK: The maximum flow in litres/second

The explanatory variables were: exposure, gender, age, (age)², smoking, weight increase, exposure group.

The data were analysed in two ways:
1. Using the group variable together with the other listed variables, except exposure.
2. Using the exposure variable together with the other listed variables, except group.

Results and discussion

Results:
EXPOSURE
The average exposure estimates for the period for the three groups were 2.3 ppbh for the low-exposure group, 4.8 ppbh for the handlers, and 8.4 ppbh (equivalent to 1.05 ppb TDI over an 8-h work shift) for the exposed group.

FINDINGS from the lung function measurements
- This study shows an annual decline of FEV1 and FVC for the entire population (n=251) of 35 ml per year and 30 ml per year, respectively. The exposed group showed the same annual declines. Regression analyses, allowing for the effects of age, gender and smoking habits, showed no relationship between the annual losses of FEV1 and FVC, and the mean daily exposure to TDI.
- Annual losses of FEV1 were smoking-dependent, with smokers having a fall of 7 ml per year greater than non-smokers. In addition, weight gain had a highly significant effect on the annual loss rate of FEV1 and FVC.
- The three occupational groups showed some substantial differences in prevalence rates of respiratory symptoms at final questionnaire and corre- sponding differences in loss rates of lung function.

FINDINGS from the questionnaire
There were marked increases in positive responses to the following questions:
- Are you troubled by shortness of breath when hurrying on level ground or walking up a slight hill? (increase common to all occupational groups and to both ex-smokers and smokers, but was largest in the small handling group).
- Does your chest ever sound wheezy or whistling? (confined to the exposed occupational group and very largely confined to smokers within that group).
- Have you ever had attacks of shortness of breath with wheezing? (confined to the exposed occupational group and in smokers).
Strengths and weaknesses:
- The study population is undoubtedly a survivor population. The choice of subjects was forced upon the investigators by the closure of factories and by large-scale redundancies in the industry over the period 1981 to 1998. From a survey of those records of leavers that were available (over 60% of all leavers from 1981 to 1998) respiratory illness was the reason for leaving given in 2.3% of cases.
- The study was not designed to identify cases of TDI sensitisation. Employees working for the participating companies received routine six-monthly health screening by company medical staff, which consisted of completion of a respiratory questionnaire and measurement of ventilatory capacity. Persons showing evidence of TDI sensitisation would be removed from further exposure to TDI and, consequently, were no longer available for selection in the current study population.

Applicant's summary and conclusion

Conclusions:
This study provides no evidence that there was any TDI-related decline in forced expiratory volume (FEV1) and forced vital capacity (FVC) over a 17-year period in workers exposed to TDI at the levels prevailing in the UK factories that manufactured flexible polyurethane foam. While this study involved TDI exposed workers, the cohort partly overlaps that of Sorahan and Nichols (2002), record 7.10.2b. The smoking profile of the females is above UK national average, which likely explains the excess lung cancer of the females reported by Sorahan and Nichols.
Executive summary:

To determine whether longitudinal declines in ventilatory capacity and the occurrence of respiratory symptoms in workers manufacturing polyurethane foam were related to toluene diisocyanate (TDI) exposure.

In an earlier study, a population of workers from 12 UK factories was studied between 1981 and 1986. A survivor cohort of 251, of whom 217 were in the 1981–1986 study, was examined again in 1997–1998. Modified British Medical Research Council respiratory questionnaires and lung function measurements were completed for each of the 251 subjects at the beginning and end of the 17-year study period. Mean TDI exposures for all jobs in which subjects were employed were assessed and related to their occupational histories.

The annual declines in 1-second forced expiratory volume (FEV1) and forced vital capacity (FVC) were not related to TDI exposure, and were typical of those measured in other populations not exposed to TDI. Over the study period the cold-foam handling group (n=26) showed an increase in breathlessness and a significant excess decline in FVC; the exposed group (n=175) showed an increase in wheezing (mainly smokers), whilst the low-exposure group (n=50) showed a decrease in chest illness. Smoking and an increase in body weight both caused excess declines in FEV1.

Overall, this study does not provide evidence that there was any TDI-related decline in FEV1 or in FVC over a 17-year period in workers exposed to TDI at the levels prevailing in the UK factories that manufactured flexible polyurethane foam.