Chronic carcinogenicity study of gasoline vapor condensate (GVC) and GVC containing methyl tertiary-butyl ether in F344 rats

Our plain-English summary of Chronic carcinogenicity study of gasoline vapor condensate (GVC) and GVC containing methyl tertiary-butyl ether in F344 rats, by J.M. Benson, A.P. Gigliotti, T.H. March, et al (Journal of Toxicology and Environmental Health. Part a, 2011).

The study

• Authors: J.M. Benson, A.P. Gigliotti, T.H. March, E.B. Barr, B.M. Tibbetts, B.J. Skipper, C.R. Clark, L. Twerdok
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2011;74(10):638-57
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m³ for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints.

In plain English

This was an animal experiment on gasoline vapor. It did not study asbestos. The authors exposed F344 rats by inhalation to vapor condensate from unleaded gasoline (GVC) or from gasoline containing methyl tertiary-butyl ether (MTBE; GMVC). For each material, 50 rats per sex per group breathed 0, 2, 10 or 20 g/m3 for 6 hours a day, 5 days a week, for 104 weeks. Exposure did not shorten lifespan. The main tumors attributed to exposure were renal tubule adenomas and carcinomas in males. These peaked at the mid level: 7 of 50 males with GVC and 6 of 50 with GMVC. Malignant mesothelioma of the testes occurred in 4 of 50 mid-level GVC males and in no controls. With GMVC, 2 of 50 high-level males had it. The authors said the GVC finding may be an exposure effect. They also said the lack of these tumors in controls may have produced a statistical signal when no causal increase was actually present. The authors concluded that MTBE did not enhance the kidney tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: two parallel chronic (2-year) whole-body inhalation carcinogenicity studies in rats, one with gasoline vapor condensate (GVC) and one with gasoline plus MTBE vapor condensate (GMVC), run under identical conditions
• Who was studied: Male and female F344 (CDF(F344)CrlBR) rats, 5 to 6 weeks old on arrival, from Charles River Laboratories. 440 rats were purchased for each study, and 400 were in the core exposure groups (50 per sex per exposure level per test material). The studies were done at Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
• Exposure: Inhaled gasoline vapor condensate, with or without MTBE (GMVC was 21.3% MTBE by analysis). Target total vapor concentrations were 0, 2, 10 or 20 g/m3. In the GMVC groups the corresponding MTBE concentrations were approximately 0.4, 2 and 4 g/m3. No asbestos or other fibers were involved.
• Main results:
  • Exposure to GVC or GMVC did not shorten lifespan compared with controls, in either sex.
  • Combined renal tubule adenomas and carcinomas in male rats peaked in the mid-level (10 g/m3) groups: 7/50 (14%) with GVC and 6/50 (12%) with GMVC. GVC high-level males had no such tumors.
  • Malignant mesothelioma of the testes occurred in 4/50 (8%) mid-level GVC males and in 0/50 controls. The authors called this a significant finding in GVC rats but not in GMVC rats.
  • In the GMVC study, testicular mesothelioma occurred in 2 of 50 (4%) high-level males, with no cases in controls. A statistical trend with exposure was found only in the GVC study.
  • Among GVC-exposed males there was a trend for increased thyroid follicular-cell carcinoma: 2 of 27 (7%) at the mid level, 0 in controls. There were no significant thyroid changes in GMVC males.
  • Nasal respiratory epithelial degeneration increased with GVC exposure. In GVC high-level females it was found at turbinate level 2 in 26 of 50 (52%), compared with 8 of 49 (16%) controls. The authors judged this lesion likely to be exposure-induced.
• The authors' conclusion: The authors concluded that, under identical conditions, GVC and GMVC produced comparable renal adenomas and carcinomas in male rats. They also concluded that MTBE was not identified as enhancing these kidney tumors compared with gasoline vapor condensate alone.
• Limitations the authors state:
  • The authors stated that the absence of testicular mesothelioma in control rats, where 1 or 2 might normally be expected in 50, may have made the statistics show an exposure-related increase in mid-level GVC males when no causal increase was actually present.
  • The authors stated that the kidney tumors arise through alpha-2 microglobulin accumulation, which does not occur in humans, so they are not predictive of human health hazard.
  • Mononuclear-cell leukemia results were attributed to sampling bias. In the low- and mid-dose groups, spleens were examined only from animals with gross lesions at necropsy.
  • The authors stated that the mechanisms that could explain the thyroid findings (DNA mutation in thyroid cells and hormone disruption) were not evaluated.

Topics

Medical terms in this study, explained in our Lexicon: Histopathology, Tubule, Carcinoma, Testicular Mesothelioma.

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