Issues of methods and interpretation in the National Cancer Institute formaldehyde cohort study

Abstract

In 2004, the International Agency for Research on Cancer (IARC) reclassified formaldehyde (FA) from a probable (Group 2A) to a known human carcinogen (Group 1) citing results for nasopharyngeal cancer (NPC) mortality from the follow-up through 1994 of the National Cancer Institute formaldehyde cohort study. To the contrary, in 2012, the Committee for Risk Assessment of the European Chemicals Agency disagreed with the proposal to classify FA as a known human carcinogen (Carc. 1A), proposing a lower but still protective category, namely as a substance which is presumed to have carcinogenic potential for humans (Carc. 1B). Thus, U.S. and European regulatory agencies currently disagree about the potential human carcinogenicity of FA.In 2013, the National Cancer Institute reported results from their follow-up through 2004 of the formaldehyde cohort and concluded that the results continue to suggest a link between FA exposure and NPC. We discuss in this commentary why we believe that this interpretation is neither consistent with the available data from the most recent update of the National Cancer Institute cohort study nor with other research findings from that cohort, other large cohort studies and the series of publications by some of the current authors, including an independent study of one of the National Cancer Institute’s study plants.Another serious concern relates to the incorrectness of the data from the follow-up through 1994 of the National Cancer Institute study stemming from incomplete mortality ascertainment. While these data were corrected by the National Cancer Institute in subsequent supplemental publications, incorrect data from the original publications have been cited extensively in recent causal evaluations of FA, including IARC. We conclude that the NCI publications that contain incorrect data from the incomplete 1994 mortality follow-up should be retracted entirely or corrected via published errata in the corresponding journals, and efforts should be made to re-analyze data from the 2004 follow-up of the NCI cohort study.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

“…The different NCI follow-up studies have been criticized for not adequately addressing heterogeneity between plants (Marsh et al 2007; McLaughlin and Tarone 2014; Marsh et al 2014). Furthermore, the statistical evaluations have been criticized for instability of the referent groups with only one NPC case in each of the metrics, for limitations in the trend test, and for the use of non-significant results in the interpretations (Marsh et al 2014).…”

“…Furthermore, the statistical evaluations have been criticized for instability of the referent groups with only one NPC case in each of the metrics, for limitations in the trend test, and for the use of non-significant results in the interpretations (Marsh et al 2014). The critique was further addressed by Marsh et al (2016) in a re-analysis of the update of the Beane Freeman et al (2013) study.…”

Hair cosmetics: An overview

“…[ 65 ] However, Marsh and cols disagree with this last decision and suggest that the NCI publications that contain data from the 1994 mortality follow-up should be re-analyzed for they understand that there is incomplete data to correlate formaldehyde exposure and NPC. [ 66 ]…”

Respiratory Symptoms due to Occupational Exposure to Formaldehyde and MDF Dust in a MDF Furniture Factory in Eastern Thailand

“…Workers are at-risk of exposure to MDF dust and formaldehyde released from the work process and the storage of raw materials and the finished products. Formaldehyde has been classified by the International Agency for Research on Cancer (IARC) as Group 1 human carcinogen [5, 6]. …”