Growing up in the 1970s, Mischief Night was a big deal for me.  When I was in grade school, hoards of us kids took to our neighborhood just after dark to wreak innocent havoc.  More fun than Halloween, I recall soaping up car windows and decorating neighbors' trees with toilet paper.  (What were our parents thinking?)

When a wonder toy called Silly String hit the stores, Mischief Night turned psychedelic with crazy vibrant colors issuing in long streams from an aerosol can!  And what was the harm?  Silly String simply dried up and blew away.  Who knew that we might actually be spewing a brew of toxic chemicals? 

Polyisobutyl methacrylate, hexabromobenzene, dibutyl phthalate, dimethyl siloxane, dichloromethane and sorbitan trioleate.  While the current formulation of Silly String is claimed to be confidential business information, these are some of the ingredients in the product's original formula.  This, according to a fun little fluff piece that ran in a recent issue of Chemical & Engineering News titled “Silly String: It’s a party for polymer chemistry, all in a can.”

Some of these chemicals — hexabromobenzene (a brominated flame retardant), dibutyl phthalate (an endocrine disruptor) and dichloromethane (also known as methylene chloride, a carcinogen) — ought to rank high on anyone's list of chemicals of concern.

But am I just being a killjoy when I ask why we should be letting our kids play with this stuff?

I don’t think so, and here is why:  While thousands of synthetic chemicals are integral parts of our modern lives, this does not mean that any chemical can and should be used in any product.  In particular, how chemicals like the ones I just noted are used should get intense scrutiny, to say the least.

It may be that some of the offending chemicals are no longer used in the current Silly String formula – but that's something we don't know because its maker is allowed to claim such information proprietary.  It may be that some of the toxic chemicals used to make the polymer fully react, so that they aren't present in the Silly String itself, at least in normal use – but we can’t know this either, because no one requires such testing for residuals.

Whatever the risk, I would still assert the following:

• Chemicals with such clear toxicity should not be used in children’s toys.  Period. 
• Workers should not have to risk being exposed to such chemicals for the purpose of making toys.
• Society should not have to risk having such chemicals released into the environment as a consequence of making toys, whether during the chemicals' or product's manufacture or transport or after disposal of the product itself.

The C&E News article highlights an unplanned and highly novel use of Silly String:  Soldiers in combat zones have learned to spray it ahead of themselves when in confined spaces to help detect the presence of deadly trip wires.  Another possible future use is as an adhesive for medical use. 

Those potentially life-saving applications for this admittedly nifty polymer technology certainly call for a different calculus, where the outcome could be quite different than for its use as a children’s toy.  (I'm not suggesting, however, that the hazards of such uses should not also be scrutinized, or that safer alternatives not be identified or sought.) 

But the problem is that, at this point, no one is even bothering to do the calculation.  It is telling that the obvious questions as to whether this use of these kinds of chemicals might pose a risk to kids, or whether it is worth taking any such risk, were not even raised by the article's author.  Nor does our current chemicals management system effectively raise them, let alone demand they be answered.

This "silly" example is yet another reminder of why EDF believes we must fundamentally reform the law that governs how we manage these kinds of chemicals.

I hate to say it, but Friends of the Earth, Consumers Union, and the International Center for Technology Assessment (ICTA) have done a disservice to good science and policy with their new superficial report Manufactured Nanomaterials and Sunscreens: Top Reasons for Precaution. There are all kinds of legitimate safety questions yet to be answered about the use of nanoscale ingredients in sunscreens, a few of which are briefly discussed in the report.  But virtually all of them apply equally to the alternative chemicals used in other sunscreens as well, a fact that the report's authors conveniently duck.

Instead, the authors cite the usual litany of effects seen in various studies of nanomaterials, most of them associated with inhalation or ingestion – exposure pathways the relevance of which they never question in their apparent haste to warn consumers off of applying nano-containing sunscreens to their skin.  They cite the "small size" of nanomaterials as the driving concern, failing to recognize that the organic molecules used in other sunscreens are typically far smaller – not to mention specifically designed to be absorbed into the skin.

Like the authors, I'm all for thorough testing, labeling and demonstration of safety of nanoscale ingredients in sunscreens and other consumer products.  But those needs extend well beyond nanoscale materials to all ingredients.  A less selective rendition of the facts about the safety of sunscreens would better serve these causes – and consumer protection.

In our critique of EPA's Chemical Assessment and Management Program (ChAMP), we have pointed out that, despite its limitations, there is value in the hazard data that EPA is collecting and analyzing.  How so?

First, we recommend that the hazard profile of the chemical be the main factor in determining a chemical's priority.  One of the reasons for this is the hazard properties are intrinsic to the chemical – they basically do not change even when the chemical is used in different ways.  Given the difficulty in knowing or anticipating all of the different applications for a chemical, the hazard data and characterization are extremely useful to have in hand for current and potential users of the chemical.

While EPA has yet to even consider the possibility, the screening-level hazard data and hazard characterizations it is developing can also help inform safer substitution.  Each ingredient in a product formulation has a specific function, for example, to reduce surface tension (surfactants), dissolve materials (solvents), reduce water hardness (chelating agents) or provide or mask a scent (fragrances).   The functional class is typically related to chemical and physical properties.

By comparing the hazard profiles of chemicals within a functional class, the chemicals with lower hazard profiles can be preferentially selected.  This is the basic approach taken by EPA's own Design for the Environment Program, which works with companies to screen product ingredients, identify chemicals of concern and identify and promote use of safer substitutes.

So how could ChAMP be used to leverage green chemistry and facilitate safer substitution?  By tagging each chemical evaluated under ChAMP with its functional class and identifying its applications (to the extent they are known).  It should then be feasible to group the ChAMP chemicals by functional class to facilitate comparison of their hazard profiles.  This information could be invaluable to companies interested in selecting safer chemical substitutes to perform a given function.

Functional class should not be confused with chemical class.  For example, within the solvent functional class, there are chemicals from many different chemical classes, including:  alcohols, esters, ethylene glycol ethers (EGEs) and propylene glycol ethers (PGEs).  While chemicals within a given chemical class may often have similar hazard properties, there will often be significant differences in hazard between the chemical classes that serve a given function.

This may not always be the case, of course.  For some functional classes and some endpoints, there may be very little difference in hazard among members because of the function that they perform.  For example, surfactants typically demonstrate aquatic toxicity because they are, by definition, surface-active.  In such cases, the entire functional class – or the underlying functionality – could be the focus of a "green chemistry challenge program" that would fund research into or otherwise seek to spur development of safer alternatives.

What would be needed to "green" ChAMP along these lines?  The following would be a start:

1. Convert the hazard data collected and analyzed in ChAMP into a sortable, searchable spreadsheet or other database that allows side-by-side comparisons.
2. Identify known applications of each ChAMP chemical.
3. Add functional class tags to each chemical.

For item # 1, tables summarizing the hazard data are already included in the hazard characterizations supporting each chemical or chemical category evaluated.  These tables simply need to be transferred into a searchable, online database.

For item #2, applications can be gleaned from a variety of sources, including information submitted by industry under the Inventory Update Rule (IUR), the Hazardous Substances Data Bank and the National Library of Medicine's Household Products Database.  The information available via these resources is often extremely limited and out-of-date.  Over time, we can expect our understanding of how chemicals are used to get better, for example as a result of data submitted under the European Union's REACH Regulation and hopefully, once the Toxic Substances Control Act is reformed.

(As is clear from our earlier posts on ChAMP, EDF has been very critical of EPA's heavy reliance on incomplete, unverified and confidential IUR information to draw conclusions about exposure and risk of HPV chemicals.  What I'm proposing here is a far more appropriate use of the IUR data, one much less sensitive to its deficiencies:  to glean any available functional use information solely for the purpose of identifying chemicals sharing a function.)

For item #3, a field can be created in the online database for functional class information. As with information on applications, functional class designations can also be difficult to obtain, but are likely to become more available in the future.

One source of both functional class and application information to consider is a subscription-based web service such as Chemidex, which compiles this type of information to facilitate information exchange among formulators.  The advantage of accessing this type of informational database is that the information comes directly from companies making products, rather than chemical manufacturers.  Still, challenges remain; for example, the listed products include mixtures, some with proprietary formulations.

Another model for this type of database is CleanGredients, which also provides information for formulators on general product and regulatory information, physical-chemical properties and human and environmental health data.

There are three needed components to forge this linkage:

Hazard Data + Functional Use + Application

Efforts like those of Chemidex and CleanGredients are beginning to provide tools able to facilitate functional use approaches to comparison and selection among chemical (and non-chemical) alternatives, albeit on a small scale and within limited categories.  With the hazard data it's collected and is now assessing under ChAMP, EPA could begin to do so on a larger scale.

In conclusion, one means of "greening" ChAMP would be to link the hazard data EPA is evaluating with meaningful functional use information.  Such an approach can start to challenge the assumption that continued production and use of high-production-volume chemicals with undesirable hazard traits is the only option.

This example raises some new issues as well as some we discussed in the earlier examples:  EPA relies on a highly flawed "category approach" that ignores major differences in the properties and structures of the 13 members of this category.  It compounds this problem by unquestioningly accepting data from inadequate studies to assert low toxicity, rather than demanding that sufficient studies be provided.  As a result, it fails to identify, let alone require to be filled, the enormous gaps in the data available for many of the category members.  EPA ignores or dismisses without explanation its own earlier comments raising serious concerns about the quality and completeness of data provided by the sponsor of these chemicals under the HPV Challenge.  Finally, this example once again shows how EPA's heavy reliance on self-reported use information from manufacturers paints an incomplete and potentially very misleading picture of the actual uses of industrial chemicals. 

The Fatty Nitrogen Derived Cationics category includes 13 chemicals that are used in industrial and consumer detergents and cleaners, as well as hair care products (conditioners or softeners), disinfectants, textile softening and antistatic agents, deodorizers, emulsifiers, dispersants, coagulants, industrial lubricants and corrosion inhibitors, among other uses.  Two supporting chemicals are registered with EPA as antimicrobial pesticides.  Annual production volumes ranged from <1 million pounds for two of the category members to 50-100 million pounds for one of the chemicals.  The sponsor of this group of chemicals under the HPV Challenge was the American Chemistry Council's Fatty Nitrogen Derivatives Panel's Cationics Task Group.

Is this a legitimate category?

EPA and international protocols provide for the grouping of chemicals into categories for data development and assessment purposes.  However, that approach starts with a hypothesis that chemicals that have structural similarities actually possess similar or predictable patterns of biological activity.  These protocols require that the hypothesis actually be demonstrated to be true, once the available data on physical-chemical properties, environmental fate and toxicity/ecotoxicity for the proposed category members are assembled, and that a full and compelling rationale be provided.

Neither the sponsor of this category nor EPA has done any such thing in the present case.  Indeed, the sparse available data do not support the category:

• Few measured physical-chemical and environmental fate data have been provided, which is essential to demonstrate similarity in properties and behavior. Instead, estimated values are provided that are either eerily identical for all category members (e.g., bioconcentration factor, or BCF) or actually vary dramatically across category members (e.g., Henry's Law Constant, which is a measure of the distribution of a chemical between water and the air above it). These findings hardly support the hypothesis that all category members will behave similarly.
• The spotty measured biodegradation data that have been provided also differ significantly (ranging from 0% degradation in 28 days, to 12% in 182 days, to 98% in 2 days). EPA acknowledges this huge range, but fails to discuss how it comports – or doesn't – with the category rationale.
• The aquatic toxicity data vary across category members by orders of magnitude. For example, acute fish toxicity values (96-hour LC50s) vary from 0.07 to 24 milligrams per liter (mg/L) – more than spanning EPA's high-moderate-low hazard classifications.
• Acute oral mammalian toxicity values (LD50s) are available for most category members – but they also vary, from 238 to >16,300 milligrams per kilogram of body weight (mg/kg-bw). And while the sponsor and EPA argue these data are similar enough to support the category (they only span EPA's moderate and low hazard classifications), there is no reason to expect that the mechanisms that impart acute toxicity are at all related to those that lead to other toxicities, such as reproductive or developmental toxicity (these endpoints are discussed further below). So how exactly do similar data for one endpoint support a conclusion that data for entirely unrelated endpoints will be comparably similar? EPA never bothers to explain this.
• As discussed below, far fewer data are available for the other human health endpoints, and what data are available do not support the category.

Despite these findings, EPA states that it agrees with the sponsor's category justification, asserting that the category members possess "similar physicochemical properties, biodegradability, aquatic toxicity, mammalian toxicity and environmental disposition patterns."  The differences in the actual data noted above are neatly set aside.

In comments EPA provided to the sponsor in 2002, EPA itself clearly considered the chemicals in this category to be sufficiently different from each other structurally that it broke them into three subcategories and argued for the need for more data to be provided within the subcategories in order to bolster the overall category.  (As we'll discuss below, the sponsor refused to provide the additional data, and EPA capitulated with nary a word as to why).  These subcategories are:  a) four chemicals that have a single alkyl chain; b) seven that have two alkyl chains; and c) a third subcategory that includes one chemical with three alkyl chains and one that has a dimeric structure.

EPA's rankings 

Now let's look at how EPA ranks the category, and some of the many reasons why we disagree.

Hazard rankings:  EPA ranks the entire chemical category as moderate for human health hazard, apparently due to the results of repeated dose testing.  While EPA maintains that none of the chemicals are expected to bioaccumulate, it expects most (9) of the category members to exhibit moderate persistence.  The hazard for aquatic organisms – fish, invertebrates and algae – is ranked high, based on the results of both acute and chronic testing using multiple test species. 

Exposure rankings:  Exposures to workers, consumers and children are expected by EPA to be high, due to the uses of these chemicals in common household and personal care products.  Releases to the environment are not known, so EPA estimated that exposures to the general public and the environment resulting from such releases would likely be moderate. 

Risk rankings:  EPA judged the risk ranking for this group of chemicals to be medium for all possible receptors. 

Prioritization ranking:  EPA assigned this chemical category a medium priority and identified a list of "possible next steps" to get additional information that would "assist EPA" to develop a better understanding of use and exposures.  These include just about everything you can imagine EPA would have needed to make any findings about exposure in the first place:  potential releases to water from manufacturing, use and disposal; information concerning worker exposures; and information concerning potential exposures to these chemicals in consumer products, such as presence and concentration and consumer use patterns.

Why We Disagree:

1.  As discussed above, the grouping of chemicals into categories can in some cases be justified, but it requires a sufficient amount of measured data to demonstrate that the chemicals within the category actually behave in a similar or predictable manner reflective of their structural similarity. In this case, the available data are grossly insufficient to support the category. Yet EPA still manages to conclude there are no data gaps for any endpoints for this entire category.

     Here is the actual extent of data for the mammalian endpoints:

Endpoint                            # Chemicals with measured data
                                            (includes 2 supporting chemicals)

Acute Oral                                                      11 of 15
Acute Dermal                                                   5 of 15
Acute Inhalation                                              2 of 15
Repeated Dose Oral                                        4 of 15
Repeated Dose Dermal                                    4 of 15
Repeated Dose Inhalation                               0 of 15
Reproductive Toxicity                                       1 of 15
Developmental Toxicity                                    5 of 15

2.  As noted earlier, EPA broke this category into three subcategories, based on structural differences. Let's examine in more detail the nature and extent of mammalian toxicity data provided for the first of these subcategories, the mono alkyl quaternary ammonium chlorides:

a. Repeated dose toxicity. None of the members of this subcategory has a reliable repeated dose toxicity study (a test that is used to evaluate health effects from more than single-dose exposures and serves as a screen for possible effects from chronic exposure). No oral studies are available, and the single dermal study provided used only a single dose. That dose yielded no adverse effects – but the dose was very low, below the dose where if an effect were seen EPA would rank the hazard as high.

Tests that use only a single dose and tests that fail to find an effect level because they use doses that are too low are insufficient to support any hazard assessment.  Yet EPA doesn't even discuss the matter.  It doesn't acknowledge the test is insufficient, nor does it identify this endpoint as a data gap, nor does it adopt a reasonable default assumption in the absence of valid data that developmental toxicity could be high.  Instead, it proceeds merrily to "read across" this negative result to the untested members of the subcategory.  And worst of all, it actually concludes in its hazard characterization summary that "no treatment-related systemic toxicity was evident at the doses tested" – completely burying critical information about data quality and reaching a scientifically unjustified conclusion.

b. Reproductive toxicity. This same subcategory lacks any reproductive toxicity data whatsoever. In comments EPA provided back in 2002 on the test plan submitted by the sponsor of this category, EPA requested that a combined reproductive/ developmental toxicity test be conducted to address this glaring gap (as well as the corresponding gap in data for developmental toxicity). The sponsor responded in 2003, stating that in its view the requested additional testing "will not further the understanding of potential human health hazards…" of these chemicals. The sponsor provided no rationale to support its claim, failing even to acknowledge EPA's point that there were no data available for any of the monoalkyls.

In EPA's current ChAMP assessment, issued in March 2009, EPA now states merely that it accepts this response, and provides absolutely no explanation for its change of heart.  Instead, EPA – without any stated justification – is now content to "read across" to all four members of this subcategory the data from a "supporting" chemical that is actually a di-alkyl, not a mono-alkyl, compound.  Indeed, this supporting chemical serves as the ONLY source of reproductive toxicity test data for all 13 category members!  On this basis, EPA then blithely claims there is no reproductive toxicity – and no data gap for reproductive toxicity – for all 13 members of this category.

c. Developmental toxicity. Data are available for one of the four members of the mono alkyl subcategory for the oral route of exposure, and for two other members for dermal exposure. EPA "reads across" these data to the untested members of the subcategory. That might normally be sufficient, but again in this case neither test yielded any adverse effects at the highest doses tested, and again those doses were very low, below the dose where if an effect were seen EPA would rank the hazard as high.

Remember, tests that fail to find an effect level because they use doses that are too low are insufficient to satisfy an endpoint and support hazard assessment.  But once again, instead of acknowledging this inadequacy, identifying this as a data gap, and using a reasonable default assumption that developmental toxicity could be high, what does EPA do?  It claims "no signs of developmental toxicity were observed"!

In its hazard characterization summary, EPA downplays or omits the results of the developmental toxicity studies it reviewed.  It ignores without explanation evidence of adverse effects that are at least equivocal, and may be significant:

• EPA claims that a test done on the di-alkyl supporting chemical "resulted in no developmental toxicity," despite the fact that increased fetal mortality and decreased fetal body weight were observed – and at doses that warrant a high hazard ranking using EPA's criteria.
• Similarly, with respect to tests done on two dialkyl category chemicals, EPA claims the studies did not produce an effect at the highest doses tested. Yet both chemicals were actually found to have increased fetal resorptions, albeit at doses that EPA would rank as low-hazard.

In each of these cases, we are forced to infer a rationale because EPA never clearly explains its decisions.  But the apparent rationales – effects seen only at doses that are also toxic to the mother, effects within the range historically observed for controls in the laboratory (though with no supporting data provided by the laboratory) – are not sufficient to conclude there are no adverse developmental effects, even if they are also insufficient to conclude there are such effects.  Indeed, in a screening-level hazard characterization based on scant or equivocal data, the default should be either to assume an effect exists or at the very least to call for further testing.

Finally, even if one were to accept these studies as definitively negative for the dialkyl subcategory, EPA has no basis either to extrapolate that finding to the other subcategories or to paper over the enormous data gap that exists for this endpoint.

3. We also disagree with EPA's risk ranking for this chemical category. Even assuming EPA's moderate ranking of the human health hazard of this group is appropriate, given that there remain important data gaps, and exposures to humans are ranked high, and the chemicals are likely to be washed down the drain into the environment, we don't see how this category should be ranked as anything but both high risk and high priority.

4. The two supporting chemicals used to provide hazard data for this category are both antimicrobials, and given EPA's readiness to treat all of the chemicals together, it is reasonable to assume that the category chemicals may also have antimicrobial properties. Add to this the facts that the chemicals in this category are used in a widespread and dispersive manner, and that they may well end up in wastewater treatment plants and surface waters, there is every reason to be concerned that they could adversely affect beneficial microbes used in wastewater treatment and found in the environment.

Antimicrobials used and marketed as such are exempted from TSCA, and are instead regulated under the Federal Insecticide, Fungicide and Rodenticide Act.  However, the chemicals in this category are used in applications where such a function and associated claims are not operative. That is, we have a group of chemicals that EPA considers similar to known antimicrobial pesticides that are disposed of down the drain, into sewage treatment systems that may not effectively remove these chemicals, potentially resulting in distribution through the ecosystem.

EPA is wholly silent on this issue.  In addition to collecting more data, we would strongly recommend that these chemicals be evaluated to determine if inherent antimicrobial properties warrant regulation as antimicrobial pesticides.

5. EPA ranks most (9) of the category members as exhibiting moderate persistence, and the remaining four as of low persistence. Yet it barely discusses the available data and ignores the following:

• Using EPA's own criteria, 3 of the 4 chemicals EPA ranked low actually exhibit moderate photodegradation rates (based on estimated data, as no measured data were provided).
• 3 of the 4 chemicals EPA ranked low for biodegradation appear to exceed EPA's criterion for a low ranking, and several of those ranked moderate show little if any biodegradation.
• EPA ranks as moderate one chemical that showed 0% degradation in 28 days. This obviously should be ranked high.
• EPA also ranks as moderate another chemical that has a half-life in soil of a whopping 1,048 days – nearly 3 years! EPA's criteria rank any half-life in soil that exceeds 180 days as high – yet EPA's ranking of this chemical is, inexplicably, moderate.
• 6 of the category members have no biodegradation data, and any rationale for EPA's implied read-across from the other members is absent.

In comments EPA provided earlier to the sponsor, EPA raised several serious concerns about the extent and nature of data provided for, and the sponsor's claims made about, biodegradation.  In the sponsor's response, it refused to do the testing EPA called for or to revise its claims that all category members are biodegradable. 

In its current ChAMP assessment, EPA seems once again to have fully capitulated:  no data gaps identified, no flagging of the enormous range in biodegradation values that calls into question the viability of the category, and a failure in contradiction of its own criteria to identify any of the category members as having high persistence.

6. EPA claims that none of the category members are expected to bioaccumulate. This is based, however, entirely on estimated data using an EPA model that yields the exact same result – a bioconcentration factor estimate of 71 – for all 13 category members. Doesn't this bear some explanation? Why can't this parameter be measured? EPA's silence is deafening.

7. Last, but not least, this ChAMP assessment amply illustrates the huge shortcomings of the use information EPA has sought to collect under its Inventory Update Rule (IUR). As we've discussed at length before, these data are of questionable value because they are self-reported by manufacturers, often incomplete because of major reporting loopholes EPA has provided, and often kept removed from any public access because EPA provides wide latitude for submitters to claim the information to be confidential. This category is a great example of these problems.

IUR submissions were received for 11 of the 13 category members.  Here's a summary of the extent of data EPA did and did not receive, and what it has not made public because of confidential business information (CBI) claims:

Types of responses in IUR submissions
Number of chemicals

*  Submitter did not submit because information is "not readily obtainable"
** Number represents CBI submissions identified as such by EPA.  EPA notes the number could be higher.

In this case, EPA has ready access to other public sources of use information for these chemicals – including, ironically, the HPV Challenge submission for this category that was provided by the same companies that under the IUR claimed such information CBI!  But in other cases, such information may not be available, as reliable and current chemical use information is very limited in general.

Given the poor performance of manufacturers reporting under the IUR, and the often very limited availability of information from other sources, how comfortable are you in EPA using these data to assess chemicals' risks to workers, the public, the environment, consumers and children?

Conclusion

In an earlier post, we characterized EPA as constructing "houses of cards" in its ChAMP assessments.  Some of you might have considered that to be awfully harsh.

But here's a classic house of cards:  EPA uses very spotty, variable, misclassified or entirely estimated data on degradation or bioconcentration to claim that this questionable category of chemicals has only low or moderate environmental persistence and bioaccumulation potential.  It then uses those findings to downgrade use information that clearly indicates these chemicals are used in a manner that culminates in down-the-drain disposal or similar release, and hence significant, ubiquitous releases to the environment – in order to claim that exposures to aquatic organisms and the general population via such releases will only be "medium."  Finally, it uses that finding to downgrade its finding of high aquatic hazard to a medium risk ranking, and to further downplay its (flawed) moderate human health hazard by finding only a medium risk to the general population.

Any questions?

Our analysis of EPA's risk decision under ChAMP for this category of toxic chemicals vividly illustrates how EPA has failed to adopt a health-protective approach to its screening of HPV chemicals.  Rather, it misclassifies or understates these chemicals' hazards, asserts that existing regulations are sufficient even when they are quite old or do not cover identified exposures, and naively assumes that children will not be as exposed as adults to consumer products used in the home unless they are intended for their use.  Finally, this case demonstrates that manufacturers are not reporting to EPA even readily available information on their chemicals' uses. 

The chlorobenzenes category is comprised of four chemicals: monochlorobenzene (CAS# 108-90-7), 1,2-dichlorobenzene (CAS# 95-50-1), 1,3-dichlorobenzene (CAS# 541-73-1) and 1,2,3-trichlorobenzene (CAS# 87-61-6).  The first three of these chemicals are on the Toxics Release Inventory (TRI).  Reported production volumes under the Inventory Update Rule and TRI emissions for 2005 and reporting manufacturers (other companies may have claimed their identity to be confidential business information) for these chemicals are as follows:

Industrial uses reported by manufacturers include use as intermediates and solvents for plastics manufacturing and basic organic chemicals manufacturing, and pesticide and other agricultural chemical manufacturing.  EPA notes other uses cited in the Hazardous Substances Data Bank (HSDB):  "pesticides, solvents, heat transfer medium, and chemical intermediates, as well as many other uses."

All members of this category were included in test rules issued under TSCA Section 4, in use and exposure-related information reporting rules issued under TSCA section 8(a), and health and safety data reporting rules issued under TSCA section 8(d).  Additionally, these chemicals are regulated under the Clean Air Act and Clean Water Act, and the Occupational Safety and Health Administration (OSHA) has set Permissible Exposure Limits (PELs) for two of the chemicals (1,2-dichlorobenzene and monochlorobenzene).

EPA considers 1,3-dichlorobenzene to be a high-priority chemical, a decision with which we agree (but see point 8 below).  It considers the other chemicals to be low-priority, and this review primarily focuses on that decision.

Hazard rankings:  EPA ranks monochlorobenzene, 1,2-dichlorobenzene and 1,2,3-trichlorobenzene as having moderate human health hazard, based on the results of repeated dose toxicity tests and developmental toxicity tests.  All three of these chemicals (as well as 1,3-dichlorobenzene and one of the supporting chemicals for the category) exhibited evidence of genotoxicity in vivo. One of the chemicals (monochlorobenzene) exhibited some, though not clear, evidence of carcinogenicity, and one of the supporting chemicals showed clear evidence of carcinogenicity.

Exposure rankings:  EPA indicates that there is a high potential for exposure to these chemicals of the general public via environmental releases, based on their reported TRI releases, environmental persistence, detection in environmental monitoring and their myriad uses.  EPA ranks worker exposures high (for two chemicals) and moderate (for the third).  Based on the use of these chemicals in consumer products, EPA ranks exposures to consumers as high and exposures to children as medium.  Interestingly, EPA reports that the IUR data – submitted by manufacturers – do not indicate uses in consumer products, but that several other sources, including the HSDB, the NIH Household Products Database, and EPA's Source Ranking Database, do indicate uses in consumer products.

Risk rankings:  EPA ranks the risks of these three chemicals to the environment to be moderate to fish and high to invertebrates and aquatic plants.  It ranks risks to the general public, consumer and children as moderate, despite their high exposure potential, based on ranking human health hazard as moderate.  EPA ranks risks to workers as low for the two chemicals with OSHA PELs (1,2-dichlorobenzene and monochlorobenzene) and moderate for 1,2,3-trichlorobenzene.

Prioritization rankings:  EPA considers all three chemicals to be low-priority because it expects existing regulations and ongoing reporting to be sufficient to mitigate risk and to alert EPA to the presence of chemicals in workplaces, environmental releases from facilities, and drinking water.

Why we disagree:

1. Given the high exposure potential to these chemicals, which EPA found to pose moderate human health hazards, even a modestly health-protective decision would rank their risks to the general public, consumers and children as high, not moderate. The potentially large number of uses, the large production volumes and TRI releases for two of the three chemicals and the substantial uncertainty regarding the magnitude, frequency, and duration of possible exposures, would support such a ranking.
        In this way, at least the development of better hazard, use and exposure information and further scrutiny of the magnitude of risks would be spurred.  Instead, EPA concludes that "No follow-up action is suggested at this time on [these three] chemicals in this category.
2. The conclusion that these chemicals are low-priority due to the existence of Clean Air Act and Clean Water Act regulations is unjustified. Despite those regulations, substantial TRI releases to air and some releases to water are being reported – sufficient for EPA to rank exposure potential as high. Yet EPA then invokes those same regulations as being adequate to prevent the very exposures it just characterized as potentially high!
3. The main reason EPA ranked consumers' and children's exposure potential high and medium, respectively, is because of expected exposures through consumer products. However, the cited CAA and CWA regulations do not address these exposures at all.
4. EPA provides no real basis for ranking children's risks lower than consumers'. EPA implies this is because it lacks evidence that these chemicals are used in products specifically intended for use by children. But EPA notes it sources of use information indicate "many other uses" for these chemicals that are not identified, and EPA provides no basis on which to conclude that uses in products not intended for use by children would not expose them. Indeed, EPA acknowledges: "Exposures to children, however, may be expected to occur through the household use of some consumer products" (p. 48 here).
5. Positive results for all of the chemicals in this category in in vivo genotoxicity studies, and for monochlorobenzene and one of the supporting chemicals in two-year carcinogenicity bioassays, clearly warrant follow-on testing to clarify the carcinogenic potential of at least the untested chemicals in this category. Yet EPA proposes no such testing; indeed it barely discusses the findings other than to repeatedly emphasize the one chemical for which negative carcinogenicity results were found.
6. In its risk rationale for children, EPA misclassifies the level of developmental toxicity for two of the three chemicals. On p. 3 here, EPA claims "available data with postnatal exposures in animals suggest a low hazard for two category members (CASRNs 95-50-1 and 108-90-7)." Yet the results of developmental toxicity tests in rats via inhalation exposure to vapors of these two chemicals actually showed moderate and high developmental toxicity, respectively, based on EPA's own criteria:
   • CAS# 95-50-1:  LOAEL ~ 2.4 mg/L/day vs. EPA range for moderate developmental toxicity of 1-2.5 mg/L/day (see pp. 27 and 38 here vs. the table on p. 12 of EPA's Methodology for Risk-Based Prioritizations under ChAMP.
   • CAS# 108-90-7:  LOAEL ~ 0.35 mg/L/day vs. EPA cutoff for high developmental toxicity of <1.0 mg/L/day (see pp. 26 and 38 here vs. the table on p. 12 of EPA's Methodology for Risk-Based Prioritizations under ChAMP
     High exposure and high or moderate developmental toxicity – surely even EPA will acknowledge these chemicals merit a high-risk and high-priority ranking?
7. EPA invokes the existence of OSHA PELs for two of these chemicals to argue that worker risk is low. Both of these PELs were promulgated in 1989 (see here and here), and at least for one of them, monochlorobenzene, NIOSH has found that "[t]he 1989 OSHA PEL may not be protective to workers."
        Were these PELs developed in consideration of and are they adequate to protect against the toxicities EPA presents herein?  While some of the test data (ca. 1984, 1987) predate the year the PELs were adopted, given the long process required to develop a PEL, the timing cannot be taken as evidence that such data were considered by OSHA.  EPA cannot merely assert that the PELs are adequate to protect workers without demonstrating that the permissible levels were set after evaluation of these data, and are still adequate in light of any other more recent toxicity data. 
        At the very least, EPA needs to engage in a meaningful referral of these data to OSHA, using its TSCA Section 9 authority, including follow-up to ensure the data have been fully considered and acted upon appropriately at OSHA.
8. Despite its high-priority finding for one of the chemicals in this category, 1,3-dichlorobenzene, EPA's only response is to state that "in order to confirm or refute the high potential risk … companies are encouraged to provide available information on a voluntary and non-confidential basis." This is clearly inadequate for such a high-risk chemical. It begs the question: what would it take for EPA to be willing to actually impose risk management on such a chemical?
9. Last but not least, EPA's finding that there are myriad product uses of these chemicals – none of which were reported by any of their manufacturers under the Inventory Update Rule (IUR) – vividly illustrates why EPA's frequent sole or primary reliance on the IUR as its source of use and exposure data for ChAMP assessments is wholly inadequate as a basis for making exposure and risk decisions for high production volume chemicals.

In May 2008, the International Center for Technology Assessment (ICTA) submitted a petition to EPA requesting that it regulate nano-silver used in products as a pesticide under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).  The petition calls on EPA to take the following specific actions:

1. Classify nano-silver as a pesticide.
2. Determine that nano-silver is a new pesticide and require its registration as such.
3. Analyze the potential risks of nano-silver to human health and the environment.
4. Take enforcement actions against nano-silver-containing products being sold illegally without EPA approval under FIFRA.

EDF supports this petition.  The rapid increase in the largely unregulated use of nano-silver in consumer products is alarming, especially given the lack of systematic evaluation of their possible harm to human health and the environment. 

As I have explained in past posts, bulk forms of silver, while having generally low direct human toxicity, have potent anti-bacterial properties and are quite toxic to many freshwater organisms.  In a recent report on nano-silver prepared for the Project on Emerging Nanotechnologies, Dr. Samuel Luoma characterized bulk-scale silver and silver ions as environmental hazards because they are toxic, persistent and bioaccumulative under at least some circumstances.  He also concluded that insufficient information is available to predict whether nano-scale silver's hazards will be comparable to or greater than those of bulk-scale silver and silver ions.   Baker and colleagues have described how silver nanoparticles appear to have greater antibacterial potency than larger-sized particles due to their larger surface area-to-volume ratio. 

Product manufacturers are seeking to capitalize on nano-silver's antimicrobial properties by adding it to dozens of products.  Many are already on the market, including nano-silver-impregnated socks and nano-silver-containing cosmetics.  That means both human contact and the release of nano-silver into the environment are already occurring, yet we are unable to predict the consequences.

So it is essential for EPA to exert its authority under FIFRA to require each manufacturer using nano-silver in a product to demonstrate that the addition of nano-silver is effective in achieving any claimed benefits, that labeling is accurate and that its use is safe for both humans and the environment. 

In a November 19, 2008 Federal Register Notice, EPA has solicited comments on this petition, with the comment period recently extended to March 20, 2009.   See that notice for details on how you can voice your opinion on this important issue.

Can nanoparticles get into our drinking water and if so, what's the harm?

Nanoparticles are being used in cosmetics and other personal care products with increasing frequency.  Carbon fullerenes, also known as buckyballs, have recently been touted as imparting age-defying antioxidant benefits when added to skin cream.  And there are some studies that seem to support these claims.  But even if such claimed benefits turn out to be true, this is by no means the end of the story. 

Skin creams are eventually washed off and down the drain.  Once they enter a sewage treatment system, the fate of nanoparticles is largely unknown.  Depending on their physical and chemical properties, engineered nanoparticles may wind up in the sludge – the solids – or they could spill over into the wastewater discharge, and wind up in lakes, rivers and streams.  If the latter occurs, they could end up in our drinking water.

This is not wild speculation.  One of the most hotly debated issues in environmental science is the frequent detection of chemicals from pharmaceuticals and personal care products in our drinking water.

If fullerenes act as antioxidants, then what's the big deal if they get into our drinking water — wouldn't they be beneficial? The very properties that allow antioxidants to scavenge the reactive oxygen species (ROS) that can damage cells also allow these compounds to liberate them, by cycling between uptake and release.  Under certain circumstances, antioxidants are more likely to release ROS than to take them up.  More research is needed to understand under what conditions so-called antioxidants might be likely to contribute to rather than prevent cell damage.

A new study published in Environmental Health Perspectives evaluated the effect of a single oral dose of fullerenes and single-walled carbon nanotubes (SWCNTs) on the extent of oxidative damage to DNA in the liver, colon and lungs of rats.  The authors were duplicating a study that demonstrated oxidative DNA damage in these organs following a single oral dose of the constituents in diesel exhaust.  DNA damage is important, because it is often a precursor to cancer.

In the new study, rats fed either fullerenes or SWCNTs exhibited increased levels of DNA damage in the liver and lungs, sometimes even at quite a low dose.  Neither nanoparticle had a significant effect on the colon at the doses tested, however.

So what does all this mean?  In my view, since we already know that chemicals in personal care products can wind up in drinking water, we should take more of a look-before-we-leap approach to evaluating new chemicals, including engineered nanomaterials, for use in these products.  This need also extends, of course, to the thousands of ingredients already present in personal care products that have not been adequately tested for safety.

Among the questions we need answered up front:  what is the expected fate and transport of such nanoparticles in the environment, who or what might be exposed during this process (including fish, bacteria, and any other critters), and if they wind up in our drinking water, what are the potential health effects?  The study discussed in this post is but one tiny piece of this puzzle.  (Of course, oral exposure to nanoparticles may occur through routes other than drinking water contamination, such as through direct ingestion of nanomaterials in foods or via the mucociliary escalator that removes inhaled particles from the lung to the digestive tract.)

Clearly we need regulators to be asking more of these questions – and requiring companies to provide the answers.  As my colleague Richard Denison pointed out in two of his recent posts, however, this doesn't appear to be happening with new chemical notifications being processed by EPA.  Instead, EPA seems to regard an absence of data as grounds for concluding an absence of risk.  And EPA gives the potential impacts at the downstream end of nanomaterials' lifecycles very short shrift.

I have just finished reading yet another depressing/infuriating publication by the Woodrow Wilson Center's Project on Emerging Nanotechnologies. The new report delineates the many limitations faced by the Consumer Product Safety Commission (CPSC) in addressing nanotechnology health risks.  The law governing the CPSC has significant weaknesses that prevent it from meeting critical needs, such as constraints on the ability to collect data, require reporting of known hazards, order recalls and promulgate mandatory safety standards.

The PEN report includes several recommendations that CPSC maximize its regulatory authority under the Consumer Products Safety Act (CPSA), and to coordinate with EPA and FDA.  The report also calls on Congress to amend the CPSA to strengthen the regulatory hand of the agency.  On paper, this seems relatively simple yet implementation will require significant political will – an attribute that seems to be in short supply these days.  That's why I'm depressed.

I'm infuriated because of the many ways PEN identifies in which a law that was conceived to protect public health has been eroded, including amendments that limit agency power (pages 15 and 17), insufficient funding (and even a political appointee who rejected funding increases) (pages 10 and 13), and inadequate staffing for enforcement (pages 16 – 17).   This neglect spans more than two decades.  With such an inglorious history, it's hard to be optimistic that change will come.

These systemic weaknesses also affect the capacity of CPSC to address hazards from conventional chemicals, with the continuing effect of toxic ignorance reinforced in the PEN report.  Of course, nanomaterials come with unique challenges relative to conventional chemicals, since nanomaterials can vary greatly in chemical composition as well as physical shape and design that can affect all aspects of health and safety risk.  As PEN's Andrew Maynard notes in his recent blog, consumer products are most likely to be the point of consumer exposures.  EPA and FDA face similar difficulties in the regulation of chemicals – and nanomaterials – used in consumer products and cosmetics. The government definitely will need some new tools in the tool box.

It is becoming increasingly clear that appropriate reform of the Toxic Substances Control Act (TSCA) can also help boost the ability of CPSC and other federal agencies to address the challenges of nanomaterials and other emerging chemicals of concern.  The Kid Safe Chemicals Act (KSCA) would substantially amend TSCA.  Among other provisions, it would require manufacturers to submit to EPA a minimum dataset on a chemical's uses, environmental and human health hazards, and exposure potential, including information critical to assessing nanomaterial risks. 

All agencies would benefit from access to the "go-to" database that KSCA calls for.  This basic chemical information could be used by any agency to help identify and prioritize hazards relevant to its mission.  CPSC could use this information to help identify chemicals of high concern for children – be they nano-scale or not.  FDA could use the database to determine if some of the most commonly used chemicals in cosmetics, which also have uses that fall under TSCA, require scrutiny.

Since the publication of the PEN report, Congress amended the CPSA to strengthen protection of children from harmful products.  In addition to essentially banning lead and certain phthalates from children's products, the CPSC will receive increased funding to boost staffing level, and laboratory and computer resources.  The CPSC will create a consumer-accessible database of safety concerns associated with products, and states will have the authority to enforce the CPSA. 

What's not clear is if these important and necessary upgrades to the CPSA will substantially improve the capacity of the CPSC to monitor and address any safety concerns that may be associated with nanotechnology in consumer products.  While the amendment directly tackles several notorious chemicals of concern, it does not appear to consider how the CPSC might generally respond to emerging concerns, such as those posed by new synthetic chemicals or novel technologies.  Time will tell if we have been given duct tape to patch holes rather than the hammer and nails required for new construction.

We often think of nanotechnology as the latest product of ultra-modern science, but humans did not invent the nanoscale. We were not even the first to use materials with nanoscale features: The gecko beat us to it by several million years. Even more impressive, this little reptile has managed to use nanoscale materials apparently without experiencing any ill effects. It remains to be seen if we will be able to do this.

Intriguing nanoscale features can be found in nature, including the “hairs” on the foot pads of the gecko, which have provided inspiration for the development of artificial adhesives, shown below in a figure from a paper recently published in the Proceedings of the National Academy of Sciences:

The photo collage illustrates how the researchers have tried to model the assembly of nanoscale features found on the gecko’s foot to engineer materials that have strong adhesive properties. The first two photos show the nanoscale features of the gecko’s foot, which consists of micrometer-sized “setae” (photo A) that are actually bundles of 100 – 200 nanometer “spatulas” (photo B). Photos C – H illustrate the researchers’ efforts to mimic these structures, by planting multi-walled carbon nanotubes (MWCNTs) on a thin, flexible surface to create a “gecko tape.” The researchers report that a 1-cm2 area of gecko tape can support nearly 4 kilograms of weight! This means that a 180-pound (82-kilogram) man could be suspended by a piece of tape no larger than the cross-section of a 2 x 4.

While I am amazed and intrigued by this novel nanoscale material, as a toxicologist, my job is to also think about the potential downsides of new technology. In a recent post, my colleague John Balbus discussed some of the serious concerns emerging about possible health effects of certain MWCNTs.

So what measures are prudent to consider before we start making and using gecko tape all over the place? Certainly, we hope that workers in the laboratory making the stuff are already taking appropriate steps to prevent incidental inhalation or ingestion. But should we be concerned about tape capable of suspending grown men from falling, for example, into the hands of college fraternities?

I also wonder whether the MWCNTs will slough off of the tape during use. If they do and are inhaled, what kind of hazard might they pose to consumers? And then there is the question of how such tape is to be disposed of ….

So while I can get as excited about these new, cool technologies as the next person, I think all of us – researchers, manufacturers, regulators and consumers – need to take the broader view and think this through before we find ourselves in a sticky situation.

Andrew Maynard, of the Project on Emerging Nanotechnologies, recently blogged about an Australian study that documented an odd effect of sunscreens containing nanoscale titanium dioxide (TiO2).  The study was prompted by the observation that installers of metal roofs who used these sunscreens inadvertently transferred the product onto the roofs. In places where the workers’ skin had touched the painted metal surfaces, the paint showed accelerated weathering. Why?  Because the particular type of nanoscale TiO2 in the sunscreen (the anatase crystal form) is photoactive – when it absorbs UV light, it releases free radicals that speed up the oxidation of the underlying paint.

So it’s only fair to ask whether the use of such sunscreens could accelerate the weathering of our skin.  Andrew says not necessarily.  While the observed damage to roof paint raises a red flag, for harm to our skin to occur would require that the free radicals penetrate down to the living layers of the skin.  That step has not (yet) been observed to occur. 

Researchers from DuPont noted that some but not all forms of nanoscale TiO2 exhibit such photoactivity.  And reactivity can be decreased (or increased) by introducing special treatments and surface coatings to either “passify” or activate such materials. 

One might have expected that sunscreen formulators would choose to use the less-reactive nanoscale TiO2.  So why do some of these sunscreens exhibit increased photoactivity?  Does this demonstrate a lack of understanding on the part of formulators, or are treatments used to reduce reactivity breaking down over time?   And is the government watching? 

So let’s review what we know and don’t know:
• We know that some forms of nanoscale TiO2 are more reactive than others.
• We know that nanoscale TiO2 can be modified to reduce reactivity.
• We know that some sunscreens that contain the more reactive form of nanoscale TiO2 can damage painted metal roofs.

But:
• We don’t know if frequent use of sunscreens containing the more reactive form of nanoscale TiO2 poses a greater health (or environmental) risk than the less reactive form.
• We don’t know what type of nanoscale TiO2 is present in any given sunscreen we may purchase (in fact we may not even know if the TiO2 is nanoscale or not).
• There’s still a lot more research needed to determine whether each of the various forms of nanoscale TiO2 can or cannot penetrate skin, including actively flexed or damaged (e.g., sunburned) skin.

Meanwhile, be careful climbing on that roof!