National Academy of Sciences Releases Strategy on Evaluating Low-Dose Effects of Endocrine Disruptors

On July 18, 2017, the National Academies of Sciences released a report detailing a strategy for evaluating the evidence of low-dose effects of endocrine disruptors (called endocrine active chemicals (EACs) in the report).  The Academies emphasized the importance of the strategy, noting that even small alterations in hormone concentrations, particularly during embryonic development, can have lasting and significant effects.

EPA asked the Academies to develop the strategy in response to evidence suggesting that some chemicals have effects at doses lower than those studied in traditional toxicity testing.  By commissioning the strategy, the Agency is working to address concerns that its current toxicity-testing protocols might be inadequate to identify all potential hazards to human health.

The strategy presents a three phase approach:

  • Surveillance for evidence that a chemical may cause a health effect or that a health effect may be missed by traditional toxicity-testing methods,
  • Investigation and analysis of the evidence, and
  • Acting on the evidence.

The Academies noted that EPA is already conducting many activities consistent with the proposed strategy.  However, the report notes that the Agency’s current approach does not necessarily use these activities to assess low-dose exposure to EACs.

The Academies made recommendations for EPA’s decision-making about its regulatory toxicity-testing practices to facilitate a greater emphasis on regular consideration of the adequacy of toxicity testing for assessing low-dose exposure to EACs.  Recommendations include:

  • Develop an active surveillance program focused specifically on low-dose exposures to EACs that includes regularly monitoring published research, gathering input from stakeholders, and considering human exposure information. The Academies recommend that the surveillance program periodically identify, scope, and prioritize potential areas of focus related to low-dose effects, such as particular chemicals and end points.
  • Use human environmental exposure or biomonitoring data to define the subset of data that should be considered as reflective of low-dose exposure.

Two examples of the application of this strategy are provided in the report.  These examples demonstrate how the strategy can be applied, and how results from its application can be integrated and considered with other relevant data to draw conclusions about causal associations.  To develop these examples, the Academies reviewed the effects of phthalates, specifically diethylhexyl phthalate (DEHP), on male reproductive-tract development and the effects of  polybrominated diphenyl ethers (PBDEs) in relation to developmental neurotoxicity.

The Academies assessment of DEHP concluded that the available data support the hazard conclusion that in utero exposure is presumed to be associated with decreased androgen production.  However, the Academies found challenges drawing conclusions about dose response.  The report explains that it is difficult to directly compare the effects of different levels of DEHP exposure in animals and humans because animal studies typically report administered doses whereas studies in humans rely on the measurement of DEHP metabolites in body fluids.  The Academies flag this as a situation where current toxicity-testing methods can identify a hazard that is presumed to be of concern to humans, but current methods might not be able to accurately predict exposures at which humans are affected.

The Academies review also identified associations between perinatal PBDE exposure and neurobehavioral outcomes.  Again the Academies found difficulties directly comparing PBDE exposure in animal studies to that occurring in humans.  In addition, the Academies report that estimates of human daily intake suggest that human exposure is several orders of magnitude lower than that used for benchmark doses in animal studies.  The Academies concluded that this is another situation where current toxicity-testing methods can identify a hazard that is presumed to be of concern to humans, but current methods might not be able to accurately predict exposures at which humans are affected.

EPA has not yet announced how it will implement the strategy.  The Agency’s efforts to research EACs are detailed on it’s website.

The full report is available here.

Ninth Circuit Vacates EPA Conditional Approval of Nanoscale Silver Antimicrobial

On May 30, 2017, the Ninth Circuit Court of Appeals vacated EPA’s conditional approval of Nanosilva NSPW-L30SWS, a type of antimicrobial silver registered as a materials preservative for textiles and plastics.  NRDC v. United States EPA, 2017 U.S. App. LEXIS 9360  (9th Cir. 2017).  The active ingredient in the product is nanoscale silver.  The National Resources Defense Council (NRDC), Center for Food Safety (CFS), and the International Center for Technology Assessment (ICTA), appealed the conditional approval. The Ninth Circuit found that EPA had not sufficiently supported its finding that early approval was in the public interest – a requirement for conditional approval under the Federal Insecticide, Fungicide, Rodenticide Act (FIFRA).  EPA granted conditional approval of the product in May 2015.

Under FIFRA, EPA is permitted to issue conditional registration for a pesticide containing an active ingredient not contained in any currently registered pesticide, only where: 1) use of that pesticide will not cause any unreasonable adverse effect on the environment, and 2) use of the pesticide is in the public interest.  7 U.S.C. § 136a(c)(7)(C).  The Ninth Circuit explained that the Agency considers this type of conditional registration when it has not received sufficient data to determine that long-term use of a pesticide is reasonable.  Id.  In its decision to grant conditional approval of NSPW, EPA found that use of the pesticide is in the public interest because it has the “potential” to reduce the amount of silver released into the environment.

NRDC, CFS, and ICTA disputed the factual premises underlying the EPA’s public-interest finding.  Petitioners challenged the Agency’s findings that:

  • NSPW has a lower application rate (e., it uses less silver) than conventional-silver pesticides;
  • NSPW has a lower mobility rate (e., it is less likely to release silver into the environment in detectable quantities); and
  • Current users of conventional-silver pesticides will switch to NSPW and/or that NSPW will not be incorporated into new products (i.e., registration of NSPW will reduce the amount of silver pesticides used).

While the Ninth Circuit found that EPA’s analysis supported finding both lower application rate and lower mobility rate, it also found that the Agency “impermissibly relie[d] on unsubstantiated assumptions” to support the finding that the conditional registration of NSPW will reduce the amount of silver pesticides used.  EPA had concluded that use of NSPW is in the public interest because it has the “potential” to reduce the amount of silver released into the environment. The Ninth Circuit held that EPA’s conclusion requires two interrelated and unstated assumptions.  The Ninth Circuit found that

  • EPA assumed that current users of conventional-silver pesticides will replace those pesticides with NSPW (“the substitution assumption”); and
  • EPA assumed that NSPW will not be incorporated into new products to the extent that such incorporation would actually increase the amount of silver released into the environment (“the no-new-products assumption”).

The Ninth Circuit held that neither assumptions are supported by substantial evidence.[1]  In fact, the Ninth Circuit found that if the EPA’s substitution and no-new-products assumptions are incorrect, NSPW may actually increase the amount of silver released into the environment, which would contravene the identified public interest.  The Ninth Circuit explained that

EPA may not satisfy the [substantial evidence] requirement by simply finding that a pesticide has the “potential” to be in the public interest—especially where the pesticide also has the “potential” to contravene the public interest. Accordingly, where an essential premise of a public-interest finding is only supported by bare assumptions, as in the present case, we will find substantial evidence lacking.

NRDC v. United States EPA, 2017 U.S. App. LEXIS 9360  (9th Cir. 2017).

[1] The Ninth Circuit held EPA to the substantial evidence standard as dictated by FIFRA.  7 U.S.C. § 136n(b).  The Court explained that “[s]ubstantial evidence means more than a mere scintilla but less than a preponderance; it is such relevant evidence as a reasonable mind might accept as adequate to support a conclusion.” Nat. Res. Def. Council v. EPA (NRDC), 735 F.3d 873, 877 (9th Cir. 2013).