Carcinogenicity in the Workplace: Threshold vs. Non-Threshold Carcinogens

Cancer presents unique challenges for workplace risk management:

• Long latency: disease may develop years or decades after exposure
• Irreversibility: outcomes are often severe and permanent 
• Cumulative risk: lifetime dose, not a single event, drives risk

Because of these characteristics, carcinogen control cannot rely solely on single measurements or compliance checks. For certain carcinogens, particularly those without a biological threshold, risk persists at any detectable exposure level and must be managed accordingly.

From an industrial hygiene perspective, carcinogens can be grouped by dose–response behavior, which is determined by biological mechanism, not regulatory classification.

Non-threshold carcinogens (typically genotoxic)

For non-threshold agents, no exposure level can be assumed completely safe. These substances can initiate carcinogenesis through direct genetic damage, meaning that even low-level exposures may contribute to cancer risk.

Implications for IH practice

• Detectable exposure equals non-zero cancer risk
• Full-shift TWAs may mask short, biologically relevant peaks
• Risk management should follow ALARA/ALARP, not rely on OEL compliance alone
• Respirators may be justified for routine tasks even below the OEL

Typical examples include benzene, hexavalent chromium (Cr VI), polycyclic aromatic hydrocarbons (PAHs), formaldehyde, ethylene oxide, and ionizing radiation.

Threshold (mechanistic-threshold) carcinogens

Threshold carcinogens generally require sufficient dose, duration, and tissue response before cancer risk helps emerge. Below this range, biological defense and repair mechanisms are typically adequate.

Implications for IH practice

• OELs are more closely aligned with low-risk exposure levels
• Cumulative dose and task frequency still matter
• ALARA remains advisable, but respirator decisions differ from genotoxic agents

Examples include crystalline silica, diesel exhaust (often mixed), welding fumes (mixed), hardwood dust, carbon black, and respirable titanium dioxide.

Mechanism determines whether a biological threshold can reasonably be assumed.

Two widely used systems inform occupational carcinogen evaluation:

• ACGIH TLV® carcinogenicity categories (A1–A5)
• IARC Monographs groups (1, 2A, 2B, 3)

These systems:

• Evaluate strength and quality of evidence linking an agent to cancer
• Do not establish safe exposure levels
• Do not indicate threshold behavior

A common misconception is that “Group 1” or “A1” automatically implies non-threshold behavior. This is incorrect. Substances with strong evidence of carcinogenicity may act through thresholded or mixed mechanisms. Consequently, mechanistic understanding—not classification alone—must guide control strategy.

This section consolidates two reference tables essential for occupational hygiene practice:

• Table 1 — Non-Threshold (Genotoxic) Carcinogens
• Table 2 — Threshold or Mechanistic-Threshold Carcinogens

Each table summarizes:

• Primary carcinogenic mechanism
• Threshold vs non-threshold behavior
• Typical occupational sources

What “below the OEL” means in practice

OELs are risk-management boundaries, not zero-risk thresholds. For non-threshold carcinogens, OEL compliance does not imply safety.

Why TWAs can understate carcinogenic risk

• Short-duration peaks may drive genotoxic events
• Full-shift averages mask task-based variability
• Repeated low-level exposures accumulate over a working lifetime

ALARA and ALARP (workplace-ready definitions)

• ALARA: Reduce exposure to the lowest achievable level (common for non-threshold carcinogens).
• ALARP: Reduce risk unless cost is grossly disproportionate to benefit; emphasizes documented decision-making.

When respirators are justified below the OEL

Respirators are typically warranted when most of the following apply:

1. The agent is non-threshold or treated conservatively as such
2. Exposure is detectable, even if well below the OEL
3. Short-term peaks are plausible or observed
4. Engineering controls cannot ensure non-detect conditions
5. Tasks are routine or repeated
6. Respirator use is low-burden and practical

Scenario
A process operator collects routine samples from benzene-containing refinery streams. Tasks involve brief bottle opening and transfer steps repeated multiple times per shift.

Findings

• Full-shift monitoring: benzene detectable; 8-hr TWA <10% of OEL
• Direct-reading data: short-duration peaks during sampling events

Interpretation
Benzene is a genotoxic, non-threshold carcinogen. Detectable exposure and short peaks indicate residual risk not reflected by the TWA alone.

Control decision

• Optimize engineering controls and work practices
• Apply ALARA by using a practical respirator (e.g., half-face with OV cartridges) during sampling tasks

Worker message
“Respirators are used here to reduce long-term cancer risk, not because limits are exceeded.”

• Mechanism determines threshold assumptions 
• Evidence classification ≠ safe level 
• For non-threshold carcinogens, detectable exposure implies residual risk 
• TWAs can mask peaks relevant to genotoxicity 
• ALARA/ALARP supports going beyond OEL compliance 
• Respirators may be justified below the OEL for routine tasks

Benzene – Mechanism & Low-Dose Risk

[1] IARC. Benzene. IARC Monographs on the Identification of Carcinogenic Hazards to Humans, Volume 120. International Agency for Research on Cancer; 2018.
Available at: https://www.iarc.who.int/news-events/iarc-monographs-volume-120-benzene/ IARC+2IARC Publications+2

[2] Lan Q, Zhang L, Li G, et al. Hematotoxicity in workers exposed to low levels of benzene. Science. 2004;306(5702):1774–1776.
Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC1256034/ PMC+1

[3] McHale CM, Zhang L, Smith MT. Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment. Carcinogenesis. 2012;33(2):240–252.
Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC3271273/ PMC+1

PAHs and Genotoxic Mechanisms

[4] Baird WM, Hooven LA, Mahadevan B. Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action.Environ Mol Mutagen. 2005;45(2–3):106–114.
PubMed: https://pubmed.ncbi.nlm.nih.gov/15688365/ PubMed+1

Hexavalent Chromium (Cr VI)

[5] Zhitkovich A. Importance of chromium-DNA adducts in mutagenicity and toxicity of chromium(VI). Chem Res Toxicol. 2005;18(1):3–11.
PubMed: https://pubmed.ncbi.nlm.nih.gov/15651842/ PubMed+1

Formaldehyde & DNA–Protein Crosslinks

[6] Ye X, Ji Z, Mei C, et al. Inhaled formaldehyde induces DNA–protein crosslinks and oxidative stress in bone marrow and other distant organs of exposed mice. Environ Mol Mutagen. 2013;54(9):705–718.
PubMed: https://pubmed.ncbi.nlm.nih.gov/24136419/ PubMed

[7] Kojima Y, Machida Y, Novotny-Diermayr V, et al. DNA-protein crosslinks from environmental exposure. (Review.) Front Genet. 2020;11:Article 1081.
Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC7575214/ PMC+1

Silica, Metals, Dusts (Threshold-Type / Inflammation Mechanisms)

[8] IARC. Arsenic, Metals, Fibres and Dusts. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100C.International Agency for Research on Cancer; 2012. (Includes crystalline silica, beryllium, etc.)
PDF (IARC): https://publications.iarc.who.int/_publications/media/download/5229/e0e75c4abc734b93870b54528986159239881730.pdf IARC Publications+2IARC Publications+2

[9] Gamble JF. Crystalline silica and lung cancer: a critical review of the epidemiologic evidence. Ann Occup Hyg. 2011;55(6):587–607.
PubMed: https://pubmed.ncbi.nlm.nih.gov/21548755/ PubMed+1

Diesel Exhaust & Particle Overload

[10] IARC. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs, Volume 105. International Agency for Research on Cancer; 2013.
NCBI Bookshelf: https://www.ncbi.nlm.nih.gov/books/NBK294269/
IARC page: https://publications.iarc.who.int/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Diesel-And-Gasoline-Engine-Exhausts-And-Some-Nitroarenes-2013 InChem+3NCBI+3NCBI+3

[11] Silverman DT, Samanic CM, Lubin JH, et al. The Diesel Exhaust in Miners Study: A nested case–control study of lung cancer and diesel exhaust. J Natl Cancer Inst. 2012;104(11):855–868.
PubMed: https://pubmed.ncbi.nlm.nih.gov/22393209/
PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC3373218/ PubMed+2PMC+2

Welding Fumes

[12] IARC. Welding, Molybdenum Trioxide, and Indium Tin Oxide. IARC Monographs, Volume 118. International Agency for Research on Cancer; 2018.
NCBI Bookshelf: https://www.ncbi.nlm.nih.gov/books/NBK543198/
IARC summary: https://monographs.iarc.who.int/news-events/volume-118-tlo/ NCBI+2NCBI+2

Arsenic & Epigenetic / Non-Genotoxic Mechanisms

[13] Bailey KA, Fry RC. Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences? Curr Environ Health Rep. 2014;1(1):22–34.
PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC4026129/ ScienceDirect+3PMC+3PubMed+3

Nickel & Epigenetics

[14] Sun H, Shamy M, Costa M. Nickel and epigenetic gene silencing. (Review.)
PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC3927569/ PMC+2PubMed+2

Cadmium – Genotoxic & Repair Inhibition

[15] Hartwig A. Cadmium and cancer. In: Sigel A, Sigel H, Sigel RKO, eds. Metal Ions in Life Sciences.2013;11:491–507.
PubMed: https://pubmed.ncbi.nlm.nih.gov/23430782/ PubMed+2PubMed+2

Regulatory / Dose–Response & ALARA/Non-Threshold Logic

[16] National Research Council. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2.National Academies Press; 2006.
NASEM: https://doi.org/10.17226/11340 ACS Publications

[17] U.S. EPA. Guidelines for Carcinogen Risk Assessment. Risk Assessment Forum; 2005.
EPA page: https://www.epa.gov/risk/guidelines-carcinogen-risk-assessment
PDF: https://www.epa.gov/sites/default/files/2013-09/documents/cancer_guidelines_final_3-25-05.pdf