This supplemental issue contains nine research articles and two
introductory/summary articles detailing recent research in occupational
exposure limits (OELs). Members of AIHA and/or ACGIH can log in to their
respective member portals to view the research articles referenced below. This blog post is a high-level summary of each of the articles, including best practices
that can be used by practicing industrial hygiene and safety professionals.
The Past and Future of Occupational Exposure Limits
This introductory article by Jonathan Borak and Lisa M.
Brosseau about “The
Past and Future of Occupational Exposure Limits” is a quick history of OELs
and analysis of the barriers present in developing new OELs. The authors note
that the ten articles “present a systematic approach that begins with an
understanding of systems biology, mechanisms of action and the early (i.e.,
“pre-clinical”) effects of toxic exposures including genetic and epigenetic
phenomena.”
The most obvious barrier to developing OELs is the lack of data
available that is relevant to human occupational exposure. Another barrier is
the difficulty in establishing global exposure limits – since countries are at
different stages of industrialization and the necessary controls may be
infeasible. The third barrier mentioned by the authors is the lack of a formal,
systematic approach to develop, establish, and update OELs.
Occupational Exposure Limit Derivation and Application
In a summary article titled “State-of-the-Science:
The Evolution of Occupational Exposure Limit Derivation and Application”
authors A. Maier, T. J. Lentz, K. L. MacMahon, L. T. McKernan, C. Whittaker,
and P. A. Schulte provide a review of the
research articles provided in the JOEH supplement. The four-page summary article explains
that the research articles in the JOEH supplement are not an exhaustive
assessment of OELs, but they explain scientific advances to be considered for risk
assessment and management of occupational hazards.
Historical Context for OELs
The first research article in this JOEH supplement is “Historical
Context and Recent Advances in Exposure-Response Estimation for Deriving
Occupational Exposure Limits” by M.W. Wheeler, R. M. Park, A. J. Bailer,
and C. Whittaker. In the abstract of the article, the authors explain that most
occupational exposure limits are not based on quantitative risk assessment (QRA),
and provide examples of exposure-response modeling methods available for QRA. “The
key step in QRA is estimation of the exposure-response relationship,” the
authors state, recommending the use of statistical tools to properly
characterize the risk.
One of the best takeaways of the article is found in
Table 1: “Common Impediments to Inference When Developing an Exposure-Response
Relationship from Epidemiological Studies.” This table presents issues such as
confounding bias, selection bias, the healthy worker effect, reverse causation,
and variable susceptibility, and provides the consequences and fixes for these
issues when working on exposure-response relationships. Table 1 is a helpful
summary for industrial hygienists or safety professionals who are just starting
their education into epidemiology.
Another helpful element of the article is found in Table
7: “OEL Estimation Methods,” which sets forth the data requirements,
considerations for use, epidemiological considerations, and caveats for
estimation methods such as the no observed adverse effect level (NOAEL),
traditional benchmark dose (BMD), and biologically-based methods. In the
conclusion of the article, the authors recommend that risk managers select the
proper “statistical methodology to estimate risks and quantify relevant
uncertainties” in occupational risks.
Dosimetry Modeling for Occupational Risk Assessment
When introducing the basic concepts of dosimetry, the
authors explain that dosimetry involves determining the amount, rate, and
distribution of a substance in the body. They also introduce the development
and use of risk-based exposure estimates including the NOAEL, the lowest observed
adverse effect level (LOAEL), and the benchmark dose (BMD), which is “the dose associated
with a specified risk (e.g., 10%) of an adverse health effect (or benchmark response)
as estimated from modeling the dose-response relationship.”
The authors explain that dosimetry is essential for
understanding the relationship between exposure and the body’s response. Dosimetry
can improve the accuracy of risk assessment by reducing the level of uncertainty
in the calculated estimates. Reliable estimates of the internal dose at the target
organ or tissue are accomplished by specific measurements or predictive models.
The article focuses on inhalation dosimetry since it is a significant route of
occupational exposure. Detailed mechanisms and models are provided for the
respiratory tract, deposition of particles of fibers, clearance and retention
of inhaled particles and fibers (including an interspecies comparison), and gas
uptake factors. The interspecies comparisons discuss that similar clearance
pathways are used by both humans and laboratory animals, but that extrapolation
of animal data for human exposure estimates has changed due to an improved
understanding of the differences between animal and human respiration.
Using Systems Biology and Biomarkers
The third research article in this JOEH supplement
presents the use of “Systems
Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting”
as written by D. Gayle DeBord, Lyle Burgoon, Stephen W. Edwards, Lynne T.
Haber, M. Helen Kanitz, Eileen Kuempel, Russell S. Thomas, and Berran Yucesoy. As
provided in the abstract of the article, this article discusses “systems
biology, biomarkers of effect, and computational toxicology approaches and
their relevance to the occupational exposure limit setting process.” In the introduction,
the authors mention the dearth of toxicity information known at present about
tens of thousands of chemicals in use in industry today.
The authors note that complex exposure scenarios, where
workers are “exposed to complex mixtures that may have additive, synergistic,
or antagonistic actions” makes it difficult to conduct thorough risk
assessments. Useful portions of this article include Table 1: “Glossary of Key
Terms.” Table 1 provides definitions for key terms used in the article,
including: benchmark dose (BMD), benchmark response (BMR), biomarkers,
computational toxicology, metabolomics, proteomics, systems biology, and
uncertainty factors.
A biomarker is an “[i]nternal [measure] or [marker] of
exposures or effects for a chemical or agent in the body.” Research into
biomarkers involves an assessment of which biomarkers can be quantitatively
linked to human adverse outcomes from occupational exposure. The authors
explain that “[e]nvironmental exposures can directly or indirectly cause alterations
in gene expression at either the transcriptional (gene expression) or the
translational level (proteomics).” Table 4: “Different Types of Biomarkers”
shows the type of biomarker (exposure, effect, or susceptibility), its characteristics,
and examples.
In the conclusion, the authors explain the advantages of
using biomarkers, since they can be used to “establish more appropriate OELs to
protect individuals who are at high risk.” They caution that the “whole field
of computational toxicology and systems biology is still evolving and results
have not been validated in human populations” and that interpretation of
biomarker results is not yet available. These challenges need to be overcome
before biomarkers can be used routinely in human occupational risk assessment.
Scientific Basis of Uncertainty Factors
An article by D. A. Dankovic, B. D. Naumann, A. Maier, M.
L. Dourson, and L. S. Levy discusses “The
Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.”
The abstract of the research article explains that “[t]he use of uncertainty
factors is predicated on the assumption that a sufficient reduction in exposure
from those at the boundary for the onset of adverse effects will yield a safe
exposure level for at least the great majority of the exposed population, including
vulnerable subgroups.”
Of interest to practicing industrial hygienists and
safety professionals, Table 1: “UFs Used in OEL-setting, and the Rationale for
Their Use” explains the types of uncertainty factors, which area of uncertainty
they are used for, and the basic principles when rationalizing their use in
risk assessment and OEL setting. For example, UFA is used for animal
to human uncertainty, and is used to adjust for differences in sensitivity
between animals and the average human (not the occupationally exposed human). Figure
5 shows the hierarchy of approaches that are available when incorporating
chemical exposure data into the risk assessment process, in order to improve
scientific certainty.
Using Genetic and Epigenetic Information
The fifth article in the JOEH supplement by P. A.
Schulte, C. Whittaker, and C. P. Curra is an introductory evaluation of “Considerations
for Using Genetic and Epigenetic Information in Occupational Health Risk
Assessment and Standard Setting.” The authors note that genetic and
epigenetic data have not been widely used in risk assessment for occupational
health. However, the authors envision that “genetic and epigenetic data might
be used as endpoints in hazard identification, as indicators of exposure, as
effect modifiers in exposure assessment and dose-response modeling, as
descriptors of mode of action, and to characterize toxicity pathways.”
When evaluating the use of epigenetics in occupational
health, the authors mention that using “epigenetics in epidemiologic studies of
occupational disease may help explain the relationship between the genome and
the work environment; however, other environmental exposures outside of work”
also will need to be controlled for. Practicing industrial hygiene and safety professionals
may be interested in Table 1: “Guide to Assessing Genetic and Epigenetic Data
for Risk Assessment,” which is a 4 × 4 matrix showing the types of risk
assessment functions (hazard identification, dose-response modeling, exposure
assessment, and risk characterization) and the questions associated with using genetic
or epigenetic data (both inherited and acquired) that may be asked.
Table 2: “Framework for use of genetic and epigenetic
data in occupational and environmental risk assessment” is also interesting, since it uses the same 4
x 4 matrix and risk assessment functions with the recommended or estimated use
of genetic and epigenetic data. For example, for the exposure assessment
function, acquired genetic data can show deviations from normal pattern of gene
expression, whereas inherited epigenetic data can be used as an indicator of
exposure.
In the conclusion, the authors state that: “It is not
far-fetched that a worker’s ‘Right to Know’ might someday extend to the
worker’s right to know their genetic susceptibility to workplace toxicants.”
This is an intriguing idea for future research.
Setting OELs for Chemical Allergens
In an interesting article about “Setting
Occupational Exposure Limits for Chemical Allergens—Understanding the
Challenges” by G. S. Dotson, A. Maier, P. D. Siegel, S. E. Anderson, B. J.
Green, A. B. Stefaniak, C. D. Codispoti, and I. Kimber, the authors discuss
establishing exposure limits for low molecular weight (LMW) chemical allergens.
The definition of chemical allergy is explained as “immune-mediated adverse
health effects, including allergic sensitization and diseases, caused by
exposures to chemicals.”
LMW allergens that are recognized occupational hazards
include: diisocyanates, organic anhydrides (i.e., maleic anhydride) and some metals
(i.e., beryllium and nickel). Table 1: “ACGIH Threshold Limit Values (TLVs)
Based on Immune-mediated Health Endpoints” provides a list of chemical
allergens with OELs already developed. These chemical allergens include
beryllium, flour dust, natural rubber latex, various diisocyanates, and
piperazine.
The article also provides an explanation of the biology
of chemical allergens, including the difference between sensitization and
elicitation, and forms of chemical allergy. The authors note that the two forms
of chemical allergy of most interest to occupational health professionals are
skin sensitization (resulting in allergic eczema and contact dermatitis) and
respiratory tract sensitization (resulting in asthma and rhinitis). Specific
challenges associated with development of OELs for chemical allergens are also
discussed.
Exposure Estimation and Interpretation of Occupational Risk
The seventh article in the JOEH supplement provides a
detailed analysis of “Exposure
Estimation and Interpretation of Occupational Risk: Enhanced Information for
the Occupational Risk Manager” by Martha Waters, Lauralynn McKernan, Andrew
Maier, Michael Jayjock, Val Schaeffer, and Lisa Brosseau. The authors explain
the risk characterization process for occupational exposures, including the
regulatory basis for OELs, describing exposures and the exposed population(s),
intrinsic variability and how to reduce uncertainty in exposure estimation, and
methods for estimating exposures.
Table 1: “Occupational Exposure Limits (OELs) Developed
by Various Organizations” shows the various OELs, which organization has set
them, and whether they were developed based on a health basis, analytical
feasibility, economic feasibility, and engineering feasibility. The authors
provide an example of the compliance approaches used by the Occupational Safety
and Health Administration (OSHA) and National Institute for Occupational Safety
and Health (NIOSH). OSHA and NIOSH’s “[approach] include[s] collecting samples
from the worst case exposure scenario or randomly from a defined similar
exposure group of interest. The measurement is compared to the OEL and is
classified into one of three decision categories: clearly below the limit,
clearly above the limit, or too close to the limit for an immediate decision.”
The authors also provide an explanation of the AIHA
exposure assessment strategy, which “recommended that [time-weighted average
(TWA)] OELs be interpreted as upper limits of exposure (e.g., 95th percentile) for
each similar exposure group (SEG) and that the exposure distribution profile of
each SEG should be controlled so that the 95th percentile exposure is less than
the OEL over time.” Following the discussion of SEGs, a short section on
Bayesian methods is provided.
Aggregate Exposure and Cumulative Risk Assessment
In this research article about “Aggregate
Exposure and Cumulative Risk Assessment—Integrating Occupational and
Non-occupational Risk Factors,” T. J. Lentz, G. S. Dotson, P. R.D. Williams,
A. Maier, B. Gadagbui, S. P. Pandalai, A. Lamba, F. Hearl, and M. Mumtaz
evaluate the benefits of considering non-occupational exposures as part of the
occupational risk assessment. The authors debate using a “combined risk from
exposure to both chemical and non-chemical stressors, within and beyond the
workplace,” with the understanding that “such exposures may cause interactions or
modify the toxic effects observed (cumulative risk).”
Like previous articles in this OEL series, the authors
provide a glossary of key terms in Table 1, including aggregate risk, exposome,
and total worker health. Exposome is defined as “the measure of all the
exposures of an individual in a lifetime and how those exposures relate to
health.” Exposomics is defined as “the study of the exposome, which relies on
the application of internal and external exposure assessment methods.”
Figure 2 of this article will be of special interest to
practicing industrial hygienists and safety professionals. It is an illustration
of the relationship between the key factors that must be considered in a
cumulative risk assessment. The primary factors are divided into three
categories: occupational factors, non-occupational factors, and individual
factors. The occupational and non-occupational factors are further divided into
settings, sources, pathways, dominant exposure routes, key stressors, and
effects. Using the illustration in Figure 2, the authors provide an
illustrative case study in Figure 3 to assess the cumulative risk for hearing
loss.
The Global Landscape of OELs
In this ninth and final research article from the JOEH
supplement, “The
Global Landscape of Occupational Exposure Limits—Implementation of
Harmonization Principles to Guide Limit Selection” is discussed by M.
Deveau, C-P Chen, G. Johanson, D. Krewski, A. Maier, K. J. Niven, S. Ripple, P.
A. Schulte, J. Silk, J. H. Urbanus, D. M. Zalk, and R. W. Niemeier. The article’s
abstract notes that an occupational hygienist seeking to determine the proper
OEL to apply in an international setting will encounter a “confusing
international landscape for identifying and applying such limits in workplaces.”
Practicing industrial hygienists and safety professionals
may be interested in Figure 1, which is a reprint of the hierarchy of
risk-based occupational exposure benchmarks as developed by AIHA in their
publications on control banding and SEGs. The authors note that the goal of international
harmonization for OEL derivation and development has been under much debate and
discussion, and explains the existing harmonization initiatives in place.
Conclusion
As occupational health and safety professionals, industrial
hygienists can have access to new and exciting research by academic,
governmental, and other groups through journals such as JOEH. In their
supplemental issue about OELs, JOEH has selected nine research articles that
provide the current state of occupational exposure science. This blog post has
summarized the contents of each article and provided takeaways and interesting
quotes from the articles, to allow practicing industrial hygiene and safety
professionals to focus their continuing safety education on the articles that
will most interest them.
