Low-level toxicity of chemicals: No acceptable levels?

Our plain-English summary of Low-level toxicity of chemicals: No acceptable levels?, by B.P. Lanphear (PLoS Biology, 2017).

The study

• Author: B.P. Lanphear
• Journal: PLoS Biology
• Published: 2017;15(12):e2003066
• Type of article: Editorial
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA) and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

In plain English

This article is a Perspective, an opinion piece, not a new study. The author discussed published research on how health effects, including disease, death, children's IQ and birth weight, change with exposure to radon, lead, fine airborne particles, asbestos, tobacco and benzene. The author argued that risk often rises most steeply at the lowest exposures (a 'decelerating' curve). The author also stated that studies had found neither regulatory model fits these substances' associations with specific conditions or causes of death. For asbestos and mesothelioma, the author cited two earlier works. A meta-analysis by Hodgson and Darnton found a curve resembling this shape, and a reanalysis of 5 cohorts of asbestos-exposed workers by Berman and Crump observed it in every cohort. The author also cited an earlier pooled analysis of children, by the author and colleagues, in which blood lead rising from below 1 to 30 μg/dL was associated with a 9.2 IQ-point deficit. The author noted unmeasured confounding might distort curve shapes and further research is needed. The author concluded that, in theory, regulators should strive for near-zero exposures to radon, lead, airborne particles, asbestos and benzene.

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: Perspective (commissioned opinion and commentary piece) discussing previously published studies; not an original study
• Who was studied: No new participants were studied. The author discussed published studies of various populations, including workers, children and atomic bomb survivors, found over more than 10 years of searching.
• Exposure: Radon and other ionizing radiation, lead, fine airborne particles (PM2.5), asbestos, tobacco smoke and benzene. No specific asbestos fiber types were named.
• Main results:
  • The author listed pairings of exposure and outcome for which other studies had reported decelerating curves: ionizing radiation with lung cancer and leukemia, lead with IQ scores, fine particles with mortality, benzene with leukemia, asbestos with mesothelioma, and tobacco and air pollution with birth weight or small-for-gestational age.
  • The author stated that a series of studies over 3 decades had found that neither regulatory assumption holds for these substances and their associations with specific conditions or causes of death. The two assumptions are a threshold for non-carcinogens and a linear, no-threshold model for carcinogens.
  • As described by the author, a meta-analysis by Hodgson and Darnton of asbestos and mesothelioma found that the exposure-response shape resembled a decelerating curve. This was an earlier study, not this article's finding.
  • As described by the author, a reanalysis by Berman and Crump of 5 cohorts of asbestos-exposed workers observed a decelerating exposure-response curve in every cohort. This was an earlier study.
  • As described by the author, an earlier pooled analysis of children's lead exposure found that an increase in blood lead from below 1 μg/dL to 30 μg/dL was associated with a 9.2-point IQ deficit. Of that deficit, 6.2 points occurred below 10 μg/dL.
  • As described by the author, a pooled analysis of 9 studies of benzene-exposed workers found leukemia relative risks of 1.52 (95% CI 1.08 to 2.15) at a cumulative exposure of 10 ppm-years, 1.73 (95% CI 1.27 to 2.34) at 20 ppm-years, and 2.11 (95% CI 1.51 to 2.96) at 40 ppm-years.
  • The author also noted a contrasting finding: a study of over 300,000 radiation-monitored workers reported a linear increase in chronic myelogenous leukemia.
• The authors' conclusion: The author concluded that, in theory, these studies indicate regulatory agencies should strive to achieve near-zero exposures for radon, lead, airborne particles, asbestos and benzene.
• Limitations the authors state:
  • Unmeasured confounders could bias or distort the shape of the exposure-response relationship. The author judged it unlikely that so many studies would share the same bias.
  • The mechanism producing the decelerating shape is less apparent for substances other than benzene.
  • Some reported decelerating curves have not been replicated. These include arsenic and lung cancer, tobacco and reading deficits, and other occupational diseases.
  • Other possible explanations include the healthy worker effect and depletion of susceptible persons.
  • Further research is needed to clarify the role of exposure assessment, explain mechanisms, and verify which chemicals show a decelerating response.

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