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Emerging Risk Issues

TERA stays at the cutting edge of developing issues. For example, current work projects address novel techniques realted to modeling chemical mixtures, assessment issues for human variability in sensitivity, and methods to address complex temporal exposure patterns. 

Examples

Assessing and Characterizing Children's Risk

Children are not simply small adults.  Assessments considering children need to consider differences in anatomy, physiology and chemical toxicokinetics and toxicodynamics.

 

Key questions for considering children’s risk include:

 

– How should risk assessors consider risk to children in developing risk values and   considering environmental and consumer product exposure?

 

– Are children more sensitive than adults?  Under what conditions?

 

Example projects include:

– Together with collaborators (Krishnan and Gentry), developed a framework for evaluating the magnitude of adult-to-child toxicokinetic differences in the inhalation dosimetry of gases

 

– Published on age-related differences in toxicokinetics and chemical sensitivity, and how these differences are taken into account in the current risk assessment paradigm (Dourson et al., 2002; Scheuplein et al., 2002).

 

– To help address differences in tissue dose to children and adults for a given environmental exposure, TERA (together with Environ) collected physiological parameters for neonatal animals for use in PBPK modeling (Gentry et al., 2005).  These data can be used to develop age-specific models to improve estimation of risk to children.

Use of Biomarker and Mode of Action Data

Evaluation of mode of action plays a critical role in both the hazard characterization and dose-response portions of assessments.  Some chemicals may be data-rich, but still lack the data addressing key issues related to MOA.  Other chemicals may have data supporting the involvement of multiple MOAs (either simultaneously or dominating different portions of the dose-response curve).  TERA can work with interested parties to design and conduct (either in-house, or in the laboratories of our collaborators) studies targeted to address key MOA questions.  We have active research projects aimed at developing approaches to quantitatively describing the dose-response for chemicals with multiple MOAs.  We are also researching approaches to quantitatively incorporate biomarker data into quantitative assessments.  These approaches allow one to use the biomarker data to inform the dose-response curve and decrease the amount of extrapolation needed, rather than simply using biomarker data to drive down the point of departure.

Key Questions

  • How much data is enough to meet EPA’s criteria for identifying a mode of action (MOA)?  What studies are needed to address EPA’s framework?
  • How can data be used to move away from default approaches, and what are the implications for risk assessment?
  • How can biomarker data be appropriately incorporated quantitatively into assessments?
  • How should assessors address new categories of materials, such as those resulting from nanotechnology?
  • How can assessments address human variability, including genetic polymorphisms and other sources of human variability?

 

TERA scientists have extensive experience with these and related issues. Example projects include [add links to publications page, etc., as noted below]:

 

  • Detailed evaluation of tumor MOA and human relevance for tumors induced by acrylamide in rats (thyroid, tunica vaginalis mesothelioma, and mammary gland). Papers in press or undergoing peer review (Dourson et al., 2008; Maier et al., 2008, submitted; Haber et al., 2009). 
  • Worked with laboratory researchers to design studies to resolve MOA issues. Example: Perchlorate
  • Published an approach using data on mutations in the tumor target tissue in transgenic animals to inform cancer MOA analysis for mutagenic carcinogens that may have other cancer MOAs (Moore et al., 2008).
  • Documented the pathophysiological progression (including biomarkers) for several endpoints. 
  • Used a Bayesian network to quantitatively incorporate data on early biomarkers of effect for benzene-induced leukemia to inform the dose-response analysis without using the biomarker directly as a point of departure (Hack et al., 2008, submitted). 
  • Evaluating lung dosimetry from inhalation exposure to nanoparticles
  • Participated in an IPCS-led effort to develop guidelines for the development of CSAFs (IPCS, 2005).
  • Used PBPK modeling and Monte Carlo analysis (in collaboration with Environ) to evaluate the impact on tissue dose of polymorphisms in genes for metabolic enzymes (Haber et al., 2002; Gentry et al., 2002).
  • Developed and presented coursesin the use of CSAFs in risk assessment, and in using the EPA framework to apply MOA data for cancer risk assessment.

Corporate Info

Resources

Our Brands

  • ITER ITER

Contacts

  • 1250 Ohio Pike, Suite 197, Cincinnati Ohio 45102
  • 513.488.1990
  • TERA@TERA.ORG

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WEEL OEL

Occupational Exposure Limits (OELs) are designed to safeguard the health of healthy workers during their careers. These limits are based on the assumption of repeated daily exposure throughout a working lifetime, typically averaged over an 8-hour workday. Their purpose is to prevent both immediate (acute) and long-term (chronic) health issues arising from workplace exposures. It’s important to note that OELs are not intended for the general public, which includes vulnerable groups like infants, the elderly, and those with pre-existing health conditions.

Workplace Environmental Exposure Levels (WEELs) are health-based guidelines for chemical hazards in the workplace. These values represent air concentrations believed to protect the majority of workers from negative health effects resulting from occupational chemical exposure.

The WEEL Process
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The development of new or revision of existing WEELs is typically assigned to voluntarily designated subcommittees. A subcommittee usually comprises 3 – 4 members from the WEEL Committee. New WEELs are developed using the OARS-WEEL administrative standard operating procedure (SOP), while existing WEELs are usually revised every 10 years, unless the availability of significant new data which may impact the existing WEEL value compels the committee to make a revision sooner. The OARS-WEEL SOP contains procedures and guidelines governing conflicts of interest, draft document preparation, literature searches, draft document review, balloting process, post-ballot WEEL documentation quality assurance scientific review, and publication.

Once a subcommittee has prepared a draft WEEL document, a review of the draft is scheduled for the next available Committee meeting. The WEEL Committee members are expected to have reviewed all such drafts prior to the meeting. If no major changes are necessary to a draft, the attending Committee membership may, by a simple majority, approve the WEEL for balloting. Alternatively, the Committee may direct the subcommittee to revise the WEEL and present it for further discussion at a future meeting. If a ballot is not approved by a two-thirds majority of non-abstaining Committee members, it is discussed at the next Committee meeting to determine the appropriate course of action. Once the WEEL is approved by a two-thirds majority of non-abstaining Committee members, copies of ballot comments are forwarded to the designated subcommittee and all substantive comments must be addressed in the final draft. If resolution of a substantive comment results in a change to the WEEL value or a change in the basis for the value, the draft must be re-balloted.

Once all comments have been addressed on a successfully balloted draft, document formatting and editorial review are performed by TERA, before the draft WEEL document is made available for public comment (usually for a period of 30 days but may be extended if the need arises). After the public comment period has elapsed, comments are addressed by the subcommittee responsible for that specific draft, after which the WEEL documentation is submitted to Toxicology and Industrial Health (TIH), a peer-reviewed medical journal that covers research in the fields of occupational health and toxicology, for publication. A thorough review of the galley proof by the scientific content quality coordinator at TERA, and proofreaders and editors at TIH is the penultimate step before eventual publication of the WEEL documentation.

The WEEL Committee

The OARS-WEEL Committee is composed of volunteer experts specializing in the scientific determination of occupational exposure levels. This committee actively seeks a balanced representation of professionals from toxicology and industrial hygiene, drawing upon a diverse range of experience from industry, government, academia, and consulting. Importantly, each member contributes to the Committee based on their individual expertise and not as an official representative of their respective employer, organization, or agency.