Identifying and Reducing Environmental Health Risks of Chemicals in Our Society Workshop Summary (2014) / Chapter Skim
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5 Approaches to Prioritizing Chemicals for Risk Assessment and Risk Management
5 Approaches to Prioritizing Chemicals for Risk Assessment and Risk Management
Pages 73-100
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From page 73... ...
, Health Canada, and the American Chemistry Council (ACC)
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From page 74... ...
There are four basic steps in this strategy: to develop highthroughput in vitro assays for testing chemicals on the biological pathways linked to toxicity, to use that information to develop predictive hazard models, to develop high-throughput exposure predictions, and to create the data and models to assess risk from the chemicals. These models can be used to prioritize chemicals for targeted testing, to distinguish possible adverse outcome pathways for chemicals, and to provide semiquantitative high-throughput risk assessments.
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From page 75... ...
That puts doing whole-genome analysis for every chemical that we are exposed to within the realm of possibility." Running hundreds of assays on thousands of chemicals results in huge datasets. The largest dataset that has been generated in the crossagency Tox212 collaboration has about 8,200 chemicals in it, including both environmental chemicals and chemicals found in consumer products (Zang et al., 2013)
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From page 76... ...
Environmental chemicals cause toxicity by interacting with specific biological molecules, Judson noted, so one can examine the various biological molecules involved in a particular adverse outcome pathway -- for example, VEGF or CCL2 or the aryl hydrocarbon receptor in the case of embryonic vascular disruption -- and examine the in vitro databases to see which environmental chemicals affect those biological molecules. "You can now start doing a reasonable job of predicting the kinds of chemicals that we have tested that might have these kinds of phenotypes."
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From page 77... ...
"This has sshown that you don't have h to solvee all the probllems for all chhemicals, butt by having thhis big daatabase, you can take speecific chemicaals and undeerstand a lot of detail of what is goiing on all the way to the tooxic endpointt." It is also possibble to model th he effects of cchemicals onn groups of ceells using what w is called d a "virtual tissue model."" With such a model one ccan simulaate the behavior of a grou up of cells orr a bit of tissuue over time -- -- say, thhe tissue in a developing limb bud. Thhe model takees into accouunt the varrious biochem mical pathway ys in the cellls and betweeen the cells thhat controol the develop pment of the limb bud, annd so it becom mes possible to observve how a particular environm mental chemiical affects thaat development.
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From page 78... ...
But if we want to do prioritization, this approach looks good enough." In addition to knowing which biochemical pathways are affected by which environmental chemicals, it is also important to know what dose of a particular chemical is necessary to produce an effect. The EPA has developed an approach to creating estimates for what it calls the biological pathway altering dose, which is the amount of a chemical necessary to turn on a particular pathway.
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From page 79... ...
The EPA has already started, Judson said, and the first outcomes should be available in about 3 years. APPROACHES TO PRIORITY SETTING IN CALIFORNIA Gina Solomon, Deputy Secretary for Science and Health at the California EPA, spoke about how the California EPA is setting priorities on environmental chemicals.
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From page 80... ...
Each program sets priorities in its own way. CalEnviroScreen Program CalEnviroScreen5 is an environmental justice screening tool, created by the Office of Environmental Health Hazard Assessment, that is used statewide (California EPA and OEHHA, 2013)
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From page 81... ...
Solomonn said that ussing such a toool to focu us assessmentts on dispropo ortionately im mpacted comm munities can be importtant in pointting to chem micals that deeserve furtherr scrutiny.
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From page 82... ...
is looking at. But it also has a scientific guidance panel that can designate and prioritize chemicals that are outside the CDC biomonitoring program list.
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From page 83... ...
Most recently, Biomonitoring California is preparing to do nontargeted testing with a time-of-flight mass spectrophotometer, which allows screening for unknown chemicals -- those that are not specifically included in current biomonitoring assays -- in environmental or biological samples. Nontargeted screening can help identify potential exposures and set priorities for testing, risk assessment, or ultimately mitigation.
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From page 84... ...
We are trying to focus on prioritizing at the product level, getting companies to look at alternatives and ultimately to move gently towards safer alternatives." From this initial list of about 1,200 candidate chemicals, the program is focusing on about 200 chemicals for the initial round of product selection, and based on these 200 it will choose a set of up to five priority consumer products. For each of these priority products there must be potential exposure to the candidate chemicals and also the potential for the exposures to contribute to or to cause significant or widespread adverse impacts.
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From page 85... ...
The 1999 amendments required the ministers of the environment and health to categorize the approximately 23,000 substances that were on the DSL, using specific criteria to identify priorities for future assessment work. Patterson noted that Environment Canada looked to see which of those 23,000 substances had the potential to be either persistent or bioaccumulative and which of those were inherently toxic to nonhuman organisms, while Health Canada looked to see which of the substances posed the greatest potential for human exposure and which ones were likely inherently toxic to humans.
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From page 86... ...
These were assessed under the Challenge Program, which consisted of a variety of individual screeninglevel assessments of the substances. 8 Further information on the Chemicals Management Plan is available at http://www.chemicalsubstanceschimiques.gc.ca/plan/index-eng.php (accessed April 2, 2014)
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From page 87... ...
. Deepending on a substance's characterisstics -- such aas whether tthe substance left the faacility where it was produ ced and whetther it was ussed by thee public, only y by industry,, or by other sectors -- thee substance w was classiffied as being in Stream 0, Stream 1, Strream 2, Streaam 3, or Streaam 4 (Streeam 0 was used u for produ ucts that werre similar in composition to petroleeum substances, but weere not mannufactured orr used by tthe petroleeum sector)
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From page 88... ...
"For substances that are used in consumer products," she said, "even if there is only a low volume in commerce, there could still be a high potential for exposure if the substance is applied directly to your skin, for example." For those substances found to not have the potential for indirect exposure and to not be used in consumer products, Health Canada concluded that further assessment work was not necessary. After carrying out three assessments on a total of approximately 1,200 substances, which were published in 2013, the agency found that approximately 700 of the substances needed no further assessment work.
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From page 89... ...
One grouping, labeled Certain Internationally Classified Substances, is not actually a group of similar substances; rather it is a group of individual substances that the planners felt warranted attention due to their international high hazard classifications. Pulling back and looking at all 4,300 substances requiring assessment as a result of categorization, Patterson offered an overview of the different assessment approaches being used (see Figure 5-4)
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From page 90... ...
Fifty-three percent of tthe substances had no hits h at all, andd 18 percent hhad very few w hits, and sinnce many of the hits forf those 18 percent are llikely to not be relevant to human n health, therre may be only o 29 perceent of the 2,,300 remaininng priority substances that have emmpirical data rrelevant to thee assessment of human n health. "I kn nly one sourcce," she said.
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From page 91... ...
, and polymers, for example, if we don't have empirical data, there is not a lot we can do." • Indirect exposures, such as through environmental media, do not typically drive human health assessment outcomes. • Instead, direct exposures -- i.e., consumer product exposures -- are more typically the key drivers in assessment outcomes.
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From page 92... ...
In 2009 the ACC published 10 principles for modernizing the Toxic Substances Control Act (TSCA) of 1976.10 One of those principles called for the EPA to systematically 10 Toxic Substances Control Act of 1976, Public Law 94-469, 94th Congress.
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From page 93... ...
The result, in ACC's view, is that there are inherent biases that exist. The priorities identified might not actually represent the highest hazard and greatest exposure potential and therefore could be a waste of time and resources on the part of the Agency." 11 Chemical Safety Improvement Act of 2013, S
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From page 94... ...
It refined the tool in 2011 so that the tool could deal with chemicals lacking sufficient information for priority setting, would be better aligned with the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) , would incorporate scientific advances regarding persistence and in bioaccumulation, and would have increased scientific rigor (ACC, 2011a)
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The tthree scores aare added together to get the total exposure sccore, which iis then used to assign substances tot an exposurre band or raange: low (3 or 4) , mediuum low (5 or 6)
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From page 96... ...
"If you are in Priority Grouping 9, any one or more of these considerations would, perhaps, move you to number one in Priority Group 9," she said. In conclusion, Franz offered a number of benefits that using the ACC prioritization tool provides: • The prioritization tool is based on objective scientific criteria regarding both hazard and exposure.
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From page 97... ...
"I like multiple approaches to priority setting," she said. "Let's do several different things and hope that we can then elevate the things that should be elevated." Luz Claudio, from Mount Sinai School of Medicine and a Roundtable member, commented that many in vitro models have been around for more than 20 years and asked Richard Judson, "Are we any closer to a clear guideline of how to use in vitro testing -- whether for screening or just to make a dent in the big list of chemicals that have not even been tested in any way?
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From page 98... ...
Again, he wondered if that could be done credibly, given that there are thousands of sites and every well will have a different mixture. In such cases, Devlin noted, it is assumed that there will have been some exposure, so he asked Judson, "Do you envision a time where the assays will be able to do that for just a hazard assessment?
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From page 99... ...
"That is not today or tomorrow. I think we will get there just because I believe that biology is not magic." As for the specific issue of the use of ToxCast for screening, Judson explained that his group had been asked a very specific question concerning the Deepwater Horizon spill.
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From page 100... ...
2013. Health Canada's experience with existing substances under the Canadian Environmental Protection Act.
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