As those making regulatory, policy, and judicial decisions assess the potential risks of a substance, several things should be taken into consideration. At the bare minimum, they should ask: are we considering all the available scientific information on this issue? Does it include rigorous research that has been peer-reviewed and replicated?
These two simple questions have driven the Center’s ongoing effort to provide independent grants to outside experts in toxicology and risk analysis to assess the validity of the published research most commonly used in the making of regulatory, policy, and judicial decisions on four key issues: PFAS, glyphosate, ethylene oxide (EtO), and talc.
We are pleased to announce that the findings of the Center’s third independent research project were recently published in Chemico-Biological Interactions, a well-regarded journal of molecular, cellular, and biochemical toxicology.
This systematic review focused on the carcinogenicity of inhaled EtO, examining the evidence surrounding EtO exposure and three types of cancer: stomach, breast, and lymphohematopoietic. It found lack of evidence of a clear and consistent relationship between EtO and all three types of cancer at current occupational exposure levels.
The findings should help address concerns, particularly of those who live nearby or work at the sterilization facilities that use EtO, as well as medical and health care professionals and hospital workers who use products sterilized by the gas. The review does not link EtO at the levels these individuals are exposed to with increased risk for the three cancers.
EtO is a gas currently used in small amounts in the sterilization of half of medical devices in the U.S., including stents, catheters, sutures, and wound care devices. It is also used in protective clothing for medical staff. This is because its properties allow for sterilization of material that other processes would harm, such as high temperatures or acids.
EtO has other advantages as well. It can travel through packaging materials allowing for sterilization of materials after they are packaged, resulting in a limited need for continued touching of the materials. It has been in use since the 1920s, and while it is also used in several other consumer products (antifreeze, plastics, etc.) its use in health care can be regarded as essential to life for many patients and health workers.
A team of researchers led by Heather Lynch, MPH, of Cardno ChemRisk conducted the review after submitting a standout proposal to our competitive and independent peer-review process for grant funding (read more on how we selected our grant recipients).
This systematic review followed the PRISMA guidelines (considered the gold standard for systematic reviews and meta-analyses) and used a hybrid framework drawn from the strongest elements in the EPA risk assessment guidelines, combined with frameworks from the Institute of Medicine (IOM) of the National Academy of Medicine—one of three academies comprising the National Academies of Sciences, Engineering, and Medicine in the United States.
Importantly, systematic, transparent, quality assessment of each of the studies was a high priority in the review. Their robust frameworks included the following:
- The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) framework (NTP, 2019)
- Integrated Risk Information System (IRIS)
- Toxic Substances Control Act (TSCA)
- The Office of Pollution Prevention and Toxics (OPPTS) Application of Systematic Review in TSCA Risk Evaluations (EPA, 2018)
- Guidance from the National Academies of Sciences, Engineering, and Medicine (NASEM)
The review identified 24 primary epidemiology and experimental animal studies and 45 mechanistic studies. The mechanistic studies confirmed what has already been reported—a genotoxic mode of action, that is, EtO can cause cancer by damaging DNA.
Toxicology studies in animals found that exposure did increase the risk for cancer, but the doses used in these studies were much higher than most human exposures. Importantly, the epidemiology studies showed no evidence of increased cancer risk at human relevant exposure to EtO, particularly in recent occupational cohort studies.
According to the U.S. National Cancer Institute (NCI), EtO has been “reported to be associated with” lymphoma and leukemia in some studies, while in others it was “reported that it may be associated with” breast and stomach cancers.
The findings of this new systematic review do not provide support for any strengthening of the NCI language. In fact, the findings indicate that more sophisticated science likely points in the opposite direction—that there is no good evidence EtO is associated with these cancers in humans at levels of exposure cited in these existing studies, with the caveat that for some rare lymphomas, there is currently not enough research to say either way.
There is a great deal of discussion happening right now regarding EtO and its applications, potential harms, contribution to low-income disparities in environmental health, and whether there are acceptable substitutes for some of its key operations in essential medical devices.
The EPA will propose new regulations for emissions from medical device sterilizers in late 2022, and its inspector general requested a new residual risk and technology review for sites that either use or produce EtO. We hope the EPA will consider the findings of this new systematic review as the agency conducts its own.
To read a summary of the findings, click here.