Formaldehyde

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Upper Airway Cancer, Myeloid Leukemia, and Other Cancers in a Cohort of British Chemical Workers Exposed to Formaldehyde

Author:

Coggon D., et al.

Year:

2014

Bibliographic source:

Am J Epidemiol. 2014 Jun 1;179(11):1301-11

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

The authors extended follow up of a cohort of 14,008 chemical workers at 6 factories in England and Wales, covering the period 1941–2012. Mortality was compared with national death rates for England and Wales, and associations with incident upper airway cancer and leukemia were explored in nested case-control analyses.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Formaldehyde

EC Number:

200-001-8

EC Name:

Formaldehyde

Cas Number:

50-00-0

Molecular formula:

CH2O

IUPAC Name:

formaldehyde

Details on test material:

- Name of test material (as cited in study report): formaldehyde

Method

Type of population:

occupational

Ethical approval:

confirmed, but no further information available

Details on study design:

A follow-up through December 2012 was conducted in the British (UK) cohort from six factories comprising 14,008 men in the period 1941–2012
Mortality was compared with national death rates for England and Wales.

At 5 factories, all male employees were enrolled, while at the sixth (British Petroleum), where only a small proportion of the workforce had been exposed to formaldehyde, recruitment was limited to formaldehyde workers and a subset of men who had worked in other parts of the plant (2 for each exposed man).

The cohort was traced through the National Health Service Central Register (now the Health and Social Care Information Centre) and in some cases national insurance records, and was followed through December 31, 2012. For men who had died, the authors obtained the underlying and contributing causes of death, coded to the Ninth (deaths through the end of 2000) or Tenth (deaths since 2000) revision of the International Classification of Diseases. For those with registered cancers, the authors obtained information on the type of cancer and the date of registration.

Additionally, a nested case-control analyses of 115 men with upper airway cancer (including 1 nasopharyngeal cancer), 92 men with leukemia, and 45 men with myeloid leukemia was performed. ORs for these cancers were independent of the duration of the exposure

Exposure assessment:

estimated

Details on exposure:

An occupational hygienist classified job titles according to their exposure to formaldehyde (background, low, moderate, high, or unknown).

Measurements of formaldehyde were not available from before 1970, but from later measurements and workers’ recall of irritant symptoms, it was estimated that background exposure corresponded to time-weighted concentrations of <0.1 ppm, low exposure to 0.1–0.5 ppm, moderate exposure to 0.6–2.0 ppm, and high exposure to >2.0 ppm.

Within each factory, each job title was assigned to the same exposure category across all time periods, but the same job title was not necessarily classified in the same exposure category at different factories.

Statistical methods:

Person-years method to compare the mortality of cohort members with that of the national population of England and Wales, according to category of exposure.

Results and discussion

Results:

Mortality in the cohort was significantly higher than expected from national rates (standardized mortality ratio (SMR) = 1.05, 95% confidence interval: 1.03, 1.08). However, the study provides no evidence that formaldehyde poses an increased hazard either of upper airway cancer or of myeloid leukemia. The increased mortality was probably attributable to non-occupational confounding factors.

Strengths and weaknesses:

The authors ascribed the increases in risk estimates to non-occupational confounding factors, which may include smoking and socioeconomic factors. It was noted that the study was not able to take smoking and socioeconomic factors into account.

Applicant's summary and conclusion

Conclusions:

Mortality in the cohort was significantly higher than expected from national rates (standardized mortality ratio (SMR) = 1.05, 95% confidence interval: 1.03, 1.08). However, the study provides no evidence that formaldehyde poses an increased hazard either of upper airway cancer or of myeloid leukemia. The increased mortality was probably attributable to non-occupational confounding factors.

Executive summary:

A follow-up through December 2012 was conducted in the British (UK) cohort from six factories comprising 14,008 men in the period 1941–2012
Mortality was compared with national death rates for England and Wales.

At 5 factories, all male employees were enrolled, while at the sixth (British Petroleum), where only a small proportion of the workforce had been exposed to formaldehyde, recruitment was limited to formaldehyde workers and a subset of men who had worked in other parts of the plant (2 for each exposed man).

The cohort was traced through the National Health Service Central Register (now the Health and Social Care Information Centre) and in some cases national insurance records, and was followed through December 31, 2012. For men who had died, the authors obtained the underlying and contributing causes of death, coded to the Ninth (deaths through the end of 2000) or Tenth (deaths since 2000) revision of the International Classification of Diseases. For those with registered cancers, the authors obtained information on the type of cancer and the date of registration.

Additionally, a nested case-control analyses of 115 men with upper airway cancer (including 1 nasopharyngeal cancer), 92 men with leukemia, and 45 men with myeloid leukemia was performed. ORs for these cancers were independent of the duration of the exposure

A total of 9,172 cohort members had exposures above the background level, including 3,991 who at some time were highly exposed. In the period, 7,378 men had died, 5,449 were still alive, and the other 1,181 had been lost to follow-up. Overall mortality in the cohort was significantly higher than expected from national rates (standardized mortality ratio (SMR) = 1.05, 95% confidence interval: 1.03, 1.08). The standardised mortality ratio [SMRs (95 % CI)] for all cancers [1.10 (1.06–1.15)], stomach [1.29 (1.11–1.49)], rectum [1.23 (1.01–1.49)], and for lung cancer [1.26 (1.17–1.35)] was significantly increased based on the national death rate for England and Wale. The nested case-control analyses of 115 men with upper airway cancer (including 1 nasopharyngeal cancer), 92 men with leukemia, and 45 men with myeloid leukemia indicated no elevations of risk in the highest exposure category (high exposure for ≥1 year). There was no excess mortality from nasopharyngeal cancer; the only death occurred in a man with low/moderate exposure (1.7 deaths expected for exposures above background).