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

Coggon, David; Ntani, Georgia; Harris, E Clare; Palmer, Keith T

doi:10.1093/aje/kwu049

Cited by 45 publications

(39 citation statements)

References 21 publications

(26 reference statements)

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“…The International Agency for Research on Cancer (IARC) working group also was not in full agreement on the evaluation of formaldehyde causing leukemia in humans (22,38). A recent paper by Coggon et al, did not find any leukemias in one of the largest cohorts of formaldehyde workers, even though some of those workers were exposed to inhaled formaldehyde at concentrations much higher than 2 ppm (37). In addition, the induction of leukemia by inhaled formaldehyde exposures has not been supported in rat carcinogenicity studies (39).…”

Section: Discussionmentioning

confidence: 98%

“…Recent epidemiological studies have suggested that exposure to formaldehyde vapors may lead to the development of hematopoietic cancers such as leukemia, however these findings remain under debate (28,33–37). While leukemia has been a major finding in epidemiology studies of inhaled formaldehyde, no mechanism for leukemia has been established.…”

Section: Discussionmentioning

confidence: 99%

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Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry

et al. 2016

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DNA-protein crosslinks (DPCs) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Due to their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally-specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([13CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous (13CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues, but were absent in tissues distant to the site of contact. This observation together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde, and may inform improved disease prevention and treatment strategies.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry

et al. 2016

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“…Quantitative FA exposures and associations with different types of cancer are available from three major and recently updated occupational cohorts: the National Cancer Institute (NCI) cohort (Beane Freeman et al 2009, 2013), the British (UK) factory cohort with exposures to FA (Coggon et al 2014), and the US NIOSH Garment Industry cohort (Meyers et al 2013). Moreover, data were also available from a case–control study of cancer among US embalmers (Hauptmann et al 2009).…”

Section: Carcinogenicitymentioning

confidence: 99%

“…Exposures were from Beane Freeman et al (2009). A British (UK) cohort from six British factories, comprising 14,008 men followed up from 1941 through December 2012; number of death were 7378 (Coggon et al 2014). The US National Institute for Occupational Safety and Health had established a cohort with 11,034 employees in three garment facilities (US garment worker cohort); number of death was 3915.…”

Section: Carcinogenicitymentioning

confidence: 99%

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

2016

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In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure–response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA’s direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin’s lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.

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“…However, whether or not inhaled formaldehyde exposure causes leukemia remains debatable. Previous experimental results have not supported the induction of leukemia (Lu et al, 2010a), and epidemiological reports have been inconsistent across different studies (Beane Freeman et al, 2009;Coggon et al, 2014). K.J.…”

mentioning

confidence: 99%

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Yu¹,

Lai²,

Hartwell³

et al. 2015

Toxicol. Sci.

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Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N 2-hydroxymethyl-dG (N 2 -HOMedG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicityinduced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N 2 -HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [ 13 CD 2 ]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t 1/2 ) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N 2 -HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency's Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair.

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

Cited by 45 publications

References 21 publications

Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry

Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry

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

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

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