Acrylamide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and scientifically acceptable report.

Data source

Reference

Reference Type:

publication

Title:

Mortality Patterns Among Workers Exposed to Acrylamide: Updated Follow Up

Author:

Marsh GM, et al

Year:

2007

Bibliographic source:

Journal of Occupational Medicine 49: 82-95

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

The objective of this study was to update the mortality experience of a cohort of workers with and without potential exposure to acrylamide at three U.S. plants (n 8508) and one plant in The Netherlands (n 344).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Acrylamide

EC Number:

201-173-7

EC Name:

Acrylamide

Cas Number:

79-06-1

Molecular formula:

C3H5NO

IUPAC Name:

prop-2-enamide

Details on test material:

Not applicable

Method

Type of population:

occupational

Ethical approval:

confirmed, but no further information available

Details on study design:

The vital status of U.S. study members was determined as of December 31, 2002, using a modified, two-stage tracing protocol based on several conventional tracing sources, including the Social Security Administration (SSA), the National Death Index-Plus (NDI) system, and state vital statistics bureaus. Subjects with “unknown” vital status were untraceable mainly due to missing Social Security numbers, a limitation of the original study due mostly to Warners employees hired before the establishment of the SSA. For deaths occurring before 1979 (beginning of NDI), death certificates were obtained from the corresponding state health departments and, to conform with the original study, were coded by a nosologist to underlying cause of death using the 8th revision rules of the International Classification of Diseases (ICD). A total of 4650 deaths through 2002, an increase of 1368 deaths from the previous 1994 follow up of the U.S. plants. This included 275 new deaths not identified in a previous 1994 update. Persons lost to follow up decreased from 513 persons (6.0%) in the original study to 386 (4.5%). Underlying cause of death was determined for 4340 or 93.3% of all deaths. Most of the 310 decedents with unknown cause of death were from the Warners plant and 124 of these died in New York City, where confidentiality rules largely restrict the release of cause of death information for research purposes. Follow up of the Botlek population was conducted through municipal population registries and the causes of death were obtained from the Central Bureau of Statistics in The Netherlands. Of the 344 workers, 233 were alive at the end of 2004, 71 were dead, and 40 (12%) were lost to follow up, mostly because of emigration. The underlying cause of death was determined for all deaths and coded to the 9th revision rules of the ICD. Data System (MPDS) maintained at the University of Pittsburgh. For the Botlek plant, corresponding Dutch national mortality rates were used (ICD 9 comparable) provided by the Dutch co-workers. Comparability between the U.S. and Dutch cause of death categories was established to the extent possible.

Exposure assessment:

estimated

Details on exposure:

0.001-0.029 mg/m3-yr
0.003-0.29 mg/m3-yr
>0.3 mg/m3-yr

Statistical methods:

The total and cause specific mortality experience of the U.S. AMD cohort from January 1, 1925, to December 31, 2002; for Botlek, the observation period was January 1, 1965, to December 31, 2004. Cohort analyses were performed using a modified life table procedure from the Occupational Cohort Mortality Program (OCMAPPlus). 26 Person-years at risk contributed by each study member were jointly classified by plant, race, age group, calendar time, duration of employment (Dur), and the time since first employment (TSFE). Person-year counts began at the date of hire and continued until date of death or the end of the 2002 or 2004 study periods. For workers lost to follow up, person-year counts stopped at the last date of known vital status, which was the date of employment termination or the date of emigration. For the U.S. cohort, we computed expected numbers of deaths by multiplying U.S. male, average annual race, age, and time-specific standard population death rates (ICD 8 comparable) by the person-years at risk in the corresponding race–age–time intervals. U.S. male death rates covering the 1925–1989 observation period were obtained from an updated version of the cohort analysis software developed by Monson.27 For the 1990–2002 period, corresponding U.S. rates were obtained for fully or nearly comparable categories from the Mortality and Population Data System (MPDS) maintained at the University of Pittsburgh. For the Botlek plant, corresponding Dutch national mortality rates (ICD 9 comparable) were provided by Dutch coworkers. Comparability between the U.S. and Dutch cause of death categories was established to the extent possible. For the U.S. plants, expected numbers of deaths based on MPDS rates for the male populations of the counties in which workers largely resided were also computed (for Warners—Middlesex and Union Counties, New Jersey; for Fortier—Jefferson Parish, Louisiana; for Kalamazoo—Kalamazoo County, Michigan).

Results and discussion

Results:

For the 1925–2002 study period, both deficit and excess overall mortality risks were observed among the U.S. cohort for cancer sites implicated in experimental animal studies: brain and other central nervous system (SMR 0.67, confidence interval [CI] 0.40 –1.05), thyroid gland (SMR 1.38, CI 0.28–4.02), testis and other male genital organs (SMR 0.64, CI 0.08 –2.30); and for sites selected in earlier exploratory analyses of this cohort: respiratory system cancer (RSC) (SMR 1.17, CI 1.06 –1.27), esophagus (SMR 1.20, CI 0.86 –1.63), rectum (SMR 1.25, CI 0.84 –1.78), pancreas (SMR 0.94, CI 0.70 –1.22), and kidney (SMR 1.01, CI 0.66 –1.46). Except for RSC, attributed earlier to muriatic acid exposure, none of the mortality excesses was statistically significant. In the Dutch cohort, deficits in deaths we observed for all sites of a priori interest. An updated analysis of previous exploratory findings for pancreatic cancer in the U.S. cohort revealed much less evidence of a possible exposure–response relationship with acrylamide.

Applicant's summary and conclusion

Conclusions:

Acrylamide exposure at the levels present in the study sites was not associated with elevated cancer mortality risks.