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Automotive Gasoline and Some Oxygenated Gasoline Additives

IARC Monographs on the Identification of Carcinogenic Hazards to Humans Volume 138

IARC

2026

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978-92-832-4538-4

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This volume of the IARC Monographs provides evaluations of the carcinogenicity of automotive gasoline and five oxygenated gasoline additives – methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), tert-butyl alcohol (TBA), diisopropyl ether (DIPE), and tert-amyl methyl ether (TAME).

Automotive gasoline (referred to hereafter as “gasoline”) is a commercial product primarily used in internal combustion engines. A complex mixture with a composition that has changed over time, it typically comprises volatile, petroleum-derived hydrocarbons, including alkanes, alkenes, and aromatics, which are blended with various additives. The oxygenated additives MTBE, ETBE, TBA, TAME, and DIPE are volatile compounds that have been used in gasoline to increase combustion efficiency, especially since the elimination of lead. All are listed as high-production-volume chemicals. The most widely used, MTBE and ETBE, are no longer added to gasoline in the USA, but are currently used in Europe, Asia, and elsewhere.

Occupational exposure to gasoline is expected mainly during the production and transport of gasoline and during vehicle refuelling, and includes occupations such as service station attendants, refinery workers, tanker truck drivers, automobile mechanics, and gasoline pump repairers and inspectors. For the oxygenated additives, workers may be exposed during production and via gasoline vapour in any of the above occupations. The general population is mainly exposed via gasoline vapour occurring at service stations, in air pollution, or in water and soil contaminated by gasoline spills.

An IARC Monographs Working Group reviewed evidence from epidemiological studies in humans, cancer bioassays in experimental animals, and mechanistic studies to assess the carcinogenic hazard to humans of exposure to these agents and concluded that:

  • Automotive gasoline is carcinogenic to humans (Group 1);
  • MTBE and ETBE are possibly carcinogenic to humans (Group 2B);
  • TBA, DIPE, and TAME are each not classifiable as to its carcinogenicity to humans (Group 3).
SUPPLEMENTARY MATERIAL
 
 
These supplementary tables are available online only. 
 
Please report any errors to imo@iarc.who.int.
 
 
The following tables were produced in draft form by the Working Group and were subsequently fact-checked and edited: 
 
Table S1.6 Air concentrations of gasoline components in and around gas stations
 
Table S1.7 Occupational exposure to gasoline, assessed using area air monitoring
 
Table S1.8 Occupational exposure to gasoline, assessed using a personal air monitoring device
 
Table S1.9 Occupational exposure to gasoline, assessed using exposure biomarkers in urine
 
The following table was produced in draft form by the Working Group and was subsequently fact-checked but not edited: 
 

Table S1.15 Exposure assessment review and critique for studies on cancer in humans exposed to automotive gasoline

 

ANNEX 2. Supplementary tables for Section 2, Cancer in humans

 
These supplementary tables are available online only.
 
Please report any errors to imo@iarc.who.int.
 
 
The following tables were produced in draft form by the Working Group and were subsequently fact-checked and edited: 
 
Table S2.5 Epidemiological studies on exposure to automotive gasoline and digestive and respiratory cancers 
 
Table S2.6 Epidemiological studies on exposure to automotive gasoline and cancer of the breast
 

Table S2.7 Epidemiological studies on exposure to automotive gasoline and other solid tumours

 

ANNEX 3. Supplementary figures for Section 2, Cancer in humans

 
These supplementary figures are available online only.
 
Please report any errors to imo@iarc.who.int.
 
These supplementary figures are related to the Working Group’s random-effects meta-analysis of epidemiological studies on the association between gasoline exposure and childhood acute lymphoblastic leukaemia, adult haematolymphoid malignancies (non-Hodgkin lymphoma, multiple myeloma; chronic lymphocytic leukaemia, acute myeloid leukaemia, myelodysplastic syndrome, and Hodgkin lymphoma), and cancers of the kidney, urinary bladder, lung, larynx, nasal cavity, stomach, and female breast. The meta-analysis is described in Section 2.8 and results are discussed in Section 2.9 of the monograph on automotive gasoline, in the present volume. Figs S2.2 to S2.27 are forest plots and Figs S2.28–2.40 are funnel plots.
 
 
Fig. S2.2 Meta-analysis for childhood acute lymphoblastic leukaemia (using self-reported exposure after expert review in McKinney et al., 2008) 
 
Fig. S2.3 Meta-analysis for childhood acute lymphoblastic leukaemia using leaded gasoline exposure in Infante-Rivard et al. (2005) 
 
Fig. S2.5 Meta-analysis for childhood acute lymphoblastic leukaemia including only studies evaluating risk by distance from service stations: sensitivity analysis excluding Harrison et al. (1999), as they used other cancer as controls, and Brosselin et al. (2009), for the use of self-reported information
 
Fig. S2.7 Meta-analysis for adult acute myeloid leukaemia or myelodysplastic syndrome (incidence only)
 
Fig. S2.11 Meta-analysis for adult chronic lymphocytic leukaemia (incidence only)
 
Fig. S2.13 Meta-analysis for adult multiple myeloma (incidence only)
 
Fig. S2.14 Meta-analysis for adult Hodgkin lymphoma
 
Fig. S2.17 Meta-analysis for kidney cancer (cohort)
 
Fig. S2.18 Meta-analysis for kidney cancer (case–control)
 
Fig. S2.21 Meta-analysis for lung cancer
 
Fig. S2.22 Meta-analysis comparing estimates for bladder and lung cancer, including only studies that reported on both cancer sites
 
Fig. S2.23 Meta-analysis for nasal cancer
 
Fig. S2.24 Meta-analysis for laryngeal cancer
 
Fig. S2.27 Meta-analysis for female breast cancer
 
Fig. S2.28 Funnel plot for childhood acute lymphoblastic leukaemia including only studies evaluating risk by distance from gasoline service station
 
Fig. S2.29 Funnel plot for adult non-Hodgkin lymphoma
 
Fig. S2.30 Funnel plot for adult multiple myeloma
 
Fig. S2.31 Funnel plot for adult acute myeloid leukaemia
 
Fig. S2.32 Funnel plot for adult acute myeloid leukaemia, excluding Talbott et al. (2011)
 
Fig. S2.33 Funnel plot for adult Hodgkin lymphoma
 
Fig. S2.34 Funnel plot for kidney cancer
 
Fig. S2.35 Funnel plot for urinary bladder cancer
 
Fig. S2.36 Funnel plot for lung cancer
 
Fig. S2.37 Funnel plot for laryngeal cancer
 
Fig. S2.38 Funnel plot for nasal cancer
 
Fig. S2.39 Funnel plot for stomach cancer
 

Fig S2.40 Funnel plot for female breast cancer

 

ANNEX 4. Supplementary material for Section 4, Mechanistic evidence 

 
These supplementary online-only tables contain summaries of the findings (including the assay name, the corresponding key characteristic, the resulting “hit calls” both positive and negative, and any reported caution flags) for those chemicals evaluated in the present volume that have been tested in high-throughput screening assays performed by the United States Environmental Protection Agency (US EPA) and the United States National Institutes of Health. The results were generated by the Working Group using the software “kc-hits” (key characteristics of carcinogens – high-throughput screening discovery tool) available from https://gitlab.com/i1650/kc-hits.git (Reisfeld et al., 2022), using the US EPA Toxicity Forecaster (ToxCast) assay data and the curated mapping of key characteristics to assays available at the time of the evaluations performed for IARC Monographs Volume 138. Data were available for methyl tert-butyl ether, ethyl tert-butyl ether, diisopropyl ether, and tert-amyl methyl ether. 
Please report any errors to imo@iarc.who.int.
 
 
 
 
 
Reference
Reisfeld B, de Conti A, El Ghissassi F, Benbrahim-Tallaa L, Gwinn W, Grosse Y, et al. (2022). kc-hits: a tool to aid in the evaluation and classification of chemical carcinogens. Bioinformatics. 38(10):2961–2. https://doi.org/10.1093/bioinformatics/btac189 PMID:35561175
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