EDF Health

FDA’s approach to systematic review of chemicals got off on the wrong foot

Scientist working on a digital tablet showing data on the chemical element Cadmium

What Happened?

Last month, FDA’s scientists published the toxicological reference value (TRV) for exposure to cadmium in the diet. This value is the amount of a chemical—in this case cadmium—a person can consume in their daily diet that would not be expected to cause adverse health effects and can be used for food safety decision-making. The TRV was based on a systematic review FDA scientists published last year. We will turn to the TRV itself in an upcoming blog but are focusing on the systematic review here.

In a May 2023 publication, experts in systematic reviews from the University of California San Francisco (UCSF) raised concerns about FDA’s “lack of compliance” from established procedures.

We discussed these concerns with FDA. They said:

  • “The systematic review and the TRV” publication “have both undergone external peer review by a third-party and experts in the field.” The agency expects to publish the reviews on its website, and
  • FDA “is working on developing a protocol for a systematic review of cardiovascular effects of cadmium exposure that will be published.”

Why It Matters

Systematic review is a method designed to collect and synthesize scientific evidence on specific questions to increase transparency and objectivity and provide conclusions that are more reliable and of higher confidence than traditional literature reviews. In particular, the National Academies of Sciences, Engineering, and Medicine have recommended the use of systematic reviews to establish values such as the TRV that may be used to inform regulatory decisions.

The National Toxicology Program (NTP) and others have developed specific methodologies to conduct systematic reviews. FDA’s authors said they followed NTP’s Office of Health Assessment and Translation (OHAT) handbook.

Unfortunately, FDA’s adherence to the methodology fell short on both transparency and objectivity grounds, undermining the credibility of its conclusions. Credibility is crucial because FDA’s authors stated that “this systematic review ultimately supports regulatory decisions and FDA initiatives, such as Closer to Zero, which identifies actions the agency will take to reduce exposures to contaminants like cadmium through foods.”

Read More »

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EDF submits extensive comments critical of EPA OPPT’s TSCA systematic review document

Ryan O’Connell is a High Meadows Fellow; Jennifer McPartland, Ph.D., is a Senior Scientist.

Last night, Environmental Defense Fund (EDF) submitted critical comments on EPA’s Office of Pollution Prevention and Toxics’ (OPPT) “systematic review” document that OPPT is using to evaluate chemicals’ risks under the Toxic Substances Control Act (TSCA).

Systematic review, a hallmark of the clinical sciences, employs structured approaches to identifying, evaluating, and integrating evidence in a manner that promotes scientific rigor, consistency, transparency, objectivity, and reduction of bias.

Unfortunately, OPPT’s systematic review document deviates dramatically from the best practices in systematic review—practices developed over decades based on empirical evidence and experience in application. OPPT’s approach also significantly diverges from recent recommendations of the National Academy of Sciences (see here and here).

Read More »

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EDF comments at EPA workshop on applying systematic review methodology to IRIS assessments

Rachel Shaffer is a research assistant.

Lately, much of the attention of the environmental health community has been focused on Capitol Hill and the Lautenberg-Vitter chemical safety reform bill that would amend the antiquated Toxic Substances Control Act (TSCA). Yet significant – if somewhat esoteric – developments are underway at EPA that will also have major impacts on how the safety of chemicals is assessed.  EPA has been implementing improvements to its Integrated Risk Information System, commonly known as “IRIS.” The purpose of the IRIS program is to evaluate information on the effects of potential exposures to environmental substances and provide health hazard assessments, which are then used to support regulatory decisions across the agency.  And while it isn’t directly affected by TSCA or its reform, IRIS provides both indirect and direct support to the office at EPA that does administer TSCA.  

In other words, what happens in IRIS doesn’t stay in IRIS.

So… what’s IRIS up to? Read More »

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Peer reviewers of EPA’s TCE report must affirm that the key risk is fetal heart damage

Richard Denison, Ph.D., is a Lead Senior Scientist.

Last week, the EPA Science Advisory Committee on Chemicals (SACC) conducted a virtual peer review meeting for the Agency’s draft risk evaluation of trichloroethylene (TCE). As expected, there was substantial discussion on the appropriateness of EPA’s decision to make risk determinations based on immune endpoints rather than fetal cardiac malformations (FCMs). Unfortunately, the review panel lacked anyone with specific expertise in cardiac development.

During the meeting, many of the peer review panelists signaled an initial inclination toward supporting EPA’s decision to use immune endpoints for risk determinations. However, panel members also noted with serious concern the recent investigations that have uncovered political influence exerted on EPA that led it to base the risk determinations in the draft risk evaluation on immune endpoints instead of FCMs.

Stepping back from the specifics of the discussions last week, it is important to understand the longstanding basis and support for EPA’s reliance on FCMs, the unprecedented nature of EPA’s decision to now move away from it, and the adverse implications of the decision for EPA’s ability to adequately manage the risks of TCE to all relevant subpopulations.

This decision is a major departure from thoroughly peer-reviewed science, fails to protect the most sensitive populations as mandated by TSCA, and deviates dramatically from existing Agency guidance. These concerns, discussed at length in EDF’s comments in the TCE Docket, are briefly summarized below:  Read More »

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EPA’s draft risk evaluation of trichloroethylene contains major scientific flaws that understate the chemical’s risk and demand robust review

Richard Denison, Ph.D., is a Lead Senior Scientist.

Yesterday Environmental Defense Fund (EDF) filed comments on the Environmental Protection Agency’s draft risk evaluation for the highly toxic chemical trichloroethylene, or TCE.

This draft, readers will recall, is the document that the Trump White House forced EPA to dramatically weaken just prior to public release, as reported in detail by Elizabeth Shogren of Reveal News.

It is also the document that EPA seems intent on subjecting to a rushed peer review next week in a 4-day virtual meeting of the Scientific Advisory Committee on Chemicals (SACC) – despite numerous reasons why, in the midst of the current COVID-19 public health crisis, such a meeting simply will not provide the robust scientific review that this draft warrants.  EDF has urged EPA to postpone the SACC review so that it can be done under circumstances that are conducive to a proper review and fair to SACC members and stakeholders who would like to participate.

EDF submitted comments yesterday in order to meet the very tight deadline EPA set for comments if they are to be considered by the SACC.  Our comments raise numerous scientific deficiencies in EPA’s draft.  These flaws arise from a host of unwarranted and unsupported assumptions and methodological approaches that systematically lead EPA to understate the risks posed by this chemical to pregnant women, infants and children; to workers; to consumers; to the public; and to the environment.

Exposure to TCE is ubiquitous, coming from ambient and indoor air, vapor intrusion from contaminated sites, groundwater and drinking water wells, and food – yet EPA’s draft ignores or downplays each of these exposure sources and pathways.

It is vital that the current public health crisis caused by COVID-19 not be allowed to compromise the quality and integrity of scientific assessments of other critical public health risks we face.

Below I summarize some of the major concerns in EPA’s draft that we address in detail in our commentsRead More »

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EPA’s scientific peer reviewers don’t mince words in blasting its 1,4-dioxane and HBCD risk evaluations

Richard Denison, Ph.D., is a Lead Senior Scientist.

Late Friday is getting to be a popular time for the toxics office at the Environmental Protection Agency (EPA) to publicly release the peer review reports of its Scientific Advisory Committee on Chemicals (SACC).

As EPA did for the Committee’s peer review report on the agency’s first draft risk evaluation under the Toxic Substances Control Act (TSCA), EPA quietly posted sometime quite late last Friday the SACC’s reports on the next two chemicals:  the likely carcinogenic solvent 1,4-dioxane and the developmentally toxic flame retardant hexabromocyclododecane (HBCD).

Even a quick read of the Executive Summaries of those reports amply illustrates why EPA sought to bury them.  I’ll focus here on 1,4-dioxane.

The SACC did note that the content and organization of this draft risk evaluation was “much improved” over the first one for Pigment Violet 29.  So much for the good news; things went downhill from there for EPA.  Read More »

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