Increasing regulatory requirements have put pressure on biocide manufacturers and have slowed the pace of new preservative introduction. The emerging challenge for formulators of water-based coatings is that fewer preservatives are available, and many of those that remain contain biocidal active substances which attract hazard communication phrases if present above a threshold trigger level. This is particularly true for European coating formulators. Against this backdrop we have formulation trends in the coatings industry, such as the removal of co-solvents, which have resulted in coatings with an increased susceptibility to in-can spoilage. These formulation changes have created an upward trend on the preservative concentrations required for robust preservation. The paint industry is facing an intensifying clash between the formulation-driven trend toward higher preservative concentrations, and the regulatory driven trend toward lower preservative concentration trigger thresholds for hazard communication. Given the headwinds impacting the historically popular in-can preservative active agents, there is likely to be a re-evaluation of antimicrobial active agents from other use patterns. For example, the pyrithione active agents, which were traditionally used as fungicides, are finding increased use as co-biocides for in-can preservation. These and other blends will be welcome new preservation tools for the coating formulator’s toolbox as the industry faces an increasingly complex regulatory environment.
Preservation – Past
Prior to the 1970s, organo-mercurial compounds were commonly used as biocides for industrial products such as paints. While they were very effective in controlling micro-organisms, they were hazardous to humans and persistent in the environment. Consequently, legislation was introduced that resulted in their phase-out and eventual ban. Organo-mercurials and other heavy metal-based biocides were removed from decorative paints in Europe in the mid-1970s, and in the United States heavy metal-based preservatives followed a similar trajectory. Organo-mercurial compounds were once extensively used in the United States, both as in-can preservatives and as film fungicides for water-based paints; however, mercury-containing biocides eventually came under regulatory pressure and the U.S. EPA cancelled all registrations for mercury-based compounds in interior line paints in 1990.
Due to the extreme safety and regulatory pressure placed on mercury-based preservatives, many synthetic organic antimicrobials were researched and developed. Among these were several different types of formaldehyde condensates, which rely on the release of free formaldehyde from the hydrolysis of a parent nitrogen-based structure. Many of these formaldehyde-condensate compounds found wide use in material preservation. While employing a common anti-microbial mechanism, these compounds represented a diverse range of both cyclic and acyclic structures. Differences in structure were associated with differences in preservation properties, with variation in features such as the rate of formaldehyde release and the sensitivity to hydrolysis at alkaline pH.
During the heyday of these compounds, a coatings formulator could select from a wide range of formaldehyde mechanism preservatives the one that gave the best fit with the needs of his or her particular coatings application. However, over time, the number of available formaldehyde-mechanism active agents has declined. There are several drivers behind this trend. First, and most obvious, are the direct regulatory headwinds faced by compounds of this type. It has long been acknowledged that exposure to formaldehyde gas is detrimental to human health. Formaldehyde gas has both acute and chronic hazards, and in 2004 formaldehyde was formally classified by the International Agency for Research on Cancer (IARC) as a human carcinogen. Given that formaldehyde-condensate compounds are very different in structure and properties from formaldehyde gas, the assessment of the risk to humans posed by the potential release of formaldehyde by these compounds is not straightforward. Nevertheless, different regulatory agencies around the world have gone in the direction of including a carcinogenicity risk assessment as part of their overall risk assessment process when they are evaluating formaldehyde-mechanism preservatives. Regulatory reviews of this type seldom lead to an outright ban on the use of a compound; however, outcomes involving restrictions on use patterns or dosage levels are commonplace.
The second headwind faced by formaldehyde-mechanism preservatives stems from the less obvious impact from changes to hazard communication requirements. Broadly speaking, paint ingredients represent a low hazard group of chemicals. Therefore, formulators of water-based coatings often begin with the assumption that they can achieve their formulation quality and performance goals without triggering the requirement for problematic hazard communication phrases (or alarming symbols) on the paint container label. By the same token, consumers of water-based coatings start with the assumption that paint represents a non-hazardous chemical and, therefore, the presence of hazard phrases on a paint container label can undermine the consumer’s perception of the safe nature of the product. In other words, hazard phrases can be problematic because they may alarm consumers and alter their buying behaviors. The relevance of this situation, in the context of formaldehyde-mechanism preservatives, is that a coatings formulator may choose to avoid using a particular preservative if the addition of that preservative would trigger a hazard communication requirement on a coating formulation that would otherwise be classified as non-hazardous. This could be described as an indirect regulatory headwind, since the preservative would still be legally available.
Lastly, there is a headwind faced by formaldehyde-mechanism preservatives from market forces. Various non-governmental organizations (NGOs) offer green-label branding for coatings products that comply with their restrictions on specific ingredients. As an example, Green Seal publishes a standard (GS-11) for paints, coatings, stains, and sealers that specifically lists formaldehyde donors as one of the prohibited ingredients. Other NGOs do not necessarily restrict formaldehyde-mechanism preservatives as specific ingredients, but they specify an upper limit for the formaldehyde content of the coating. As an example, the Blue Angel publishes an environmental label criterion for low-emission interior wall paints which states that the free-formaldehyde content of such coatings shall not exceed 100 ppm. These restrictions from NGOs represent another indirect headwind, in that, while the NGOs do not have the authority to change the regulatory status of preservatives, they can nevertheless cause certain preservatives to fall out of favor.
In summary, in the days since the ban on mercurial biocides, formaldehyde-mechanism preservatives have encountered both direct and indirect barriers to their use. While members of this class of compounds are still available in the marketplace, the coatings formulator of today has a narrower range of formaldehyde-mechanism preservatives to choose from. This makes it less likely that the selected active agent will be a good fit with the needs of a particular coatings application.
Preservation – Present
Members of the isothiazolinone class of preservatives have long been available as alternatives to organo-mercurials and formaldehyde-mechanism preservatives. However, the more recent decline in the variety of formaldehyde-mechanism preservatives has provided an additional incentive for formulators to evaluate isothiazolinone preservatives as alternative options.
Members of the isothiazolinone chemical family contain an isothiazolinone ring with an activated N-S bond which can react with nucleophilic cell entities and thus exert antimicrobial activity. Beginning in the 1960s and 70s, one of these isothiazolinone derivatives (1,2-benzisothiazolin-3-one, BIT) became available as a non-formaldehyde-mechanism alternative preservative for industrial products. Since that time other isothiazolinone derivatives have become available, and usage of isothiazolinone biocides has grown to the point where today they represent one of the major types of biocides used for material protection. Derivatives of isothiazolinone are used as both anti-bacterial, in-can preservatives and as anti-fungal, dry-film preservatives. Other examples of isothiazolinone biocides include; MIT (2-Methylisothiazol-3(2H)-one), CMIT/MIT (5-Chloro-2-methyl-4-isothiazolin-3-one/2-Methylisothiazol-3(2H)-one), OIT (2-Octyl-2H-isothiazol-3-one), BBIT (2-Butyl-1,2-benzisothiazolin-3-one), and DCOIT (4,5-Dichloro-2-n-octyl-3(2H)-isothiazolone).
Isothiazolinone biocides represent a step away from the broadly toxic and highly persistent first-generation group of biocides and, unlike formaldehyde-condensate biocides, they are not associated with a carcinogen. Nevertheless, in some regions, isothiazolinone biocides have begun to experience the sort of indirect headwinds associated with changes to hazard communication requirements. In developing an understanding of the current situation it is helpful to first review some background.
All of the commonly used isothiazolinone biocide active agents are either known or potential skin sensitizers. As a consequence of this fact, hazard communication regulations can impact the labeling required for materials protected with isothiazolinone biocides. This is particularly true in Europe.
In Europe in the 1990s the Biocidal Products Directive (BPD) was implemented across the European Union. The major intention of this directive was to ensure that biocidal products covering in-scope applications demonstrated an acceptable human health and environmental use profile in a consistent process across the EU. Throughout the active substances evaluation phase of the BPD, many actives have disappeared from the market in part due to the high costs associated with supporting active substances and the requirement for compliance with ever-stricter risk assessments. In 2012, the Biocidal Products Regulation (BPR) replaced the BPD. This legislation, now a regulation, corrected and strengthened the previous BPD to further regulate the use of biocidal products within the EU marketplace.
The Classification, Labeling and Packaging (CLP) Regulation (1272/2008/EC), the EU implementation of the United Nation’s Global Harmonized System (GHS), replaced both the Dangerous Substances Directive 67/548/EEC and more recently, in June 2015, the Dangerous Preparations Directive (DPD) 1999/45/EC. This has updated the classification and labeling requirements within the EU.
In the context of isothiazolinone biocides, there was a recent key change in labeling that was introduced in the second Adaptation to Technical Progress (ATP) update to the CLP Regulation (published in 2011), which contains changes in the classification and labeling criteria for substances and mixtures regarding sensitization. This change potentially places a new obligation onto the customer’s preserved products that was previously not required. This potential change may impact the suitability of a sensitizing biocide in a customer’s product. Note that this regulation is not specific to isothiazolinones but rather covers any chemical associated with a sensitization classification. However, as mentioned earlier, all of the commonly used isothiazolinone biocide active agents are either known or potential skin sensitizers.
The CLP regulation now establishes two sub-categories of skin sensitizer:
• Category 1A High Potency
• Category 1B Moderate-Low Potency
In the past, a mixture had to be classified as sensitizing if it contained >= 1 % of a sensitizing component, unless the legal classification from Annex VI for the CLP contained a different specific concentration limit (SCL).
Any mixture not classified as sensitizing but containing a sensitizing component at >= 0.1% needed to carry an additional statement on the label, the so-called “Allergen Phrase” -- “Contains (name of sensitizing substance). May produce an allergic reaction.”
This wording was already required in the former EU DPD. The revised CLP introduced a differentiation for substance classification between “high-potency sensitizers” and “moderate-low potency sensitizers”. The concentration threshold for the classification of mixtures has been lowered to >= 0.1% for strong sensitizers; other sensitizers stay at 1%.
In addition, the concentration threshold for elicitation (the Allergen Phrase) has been lowered to 0.01% for strong sensitizers. For any sensitizing substance with an SCL of less than 0.1% the limit has been set to one tenth (1/10) of the SCL.
Under CLP the Allergen Phrase is referred to as EU H208. It is important to note that this phrase and the application criteria are not part of the UN GHS model regulations but a specific “EU add-on.” This phrase is not mandatory outside the EU.
To summarize, within the European Union, hazard communication requirements for chemical mixtures in the context of sensitizing chemicals changed in June of 2015. Many of the preservative systems currently selected by coatings formulators within the European Union were selected to meet the challenge of avoiding the EU H208 allergen phrase. However, in the time since June of 2015 a new challenge for coatings formulators has appeared on the horizon. Once again, in developing an understanding of the future challenge, it is helpful to first review some background.
As described above, for some sensitizing compounds, Annex VI for the CLP describes individual specific concentration limits (SCL). If such a compound is present in a coating formulation above its specific concentration limit, then the coating formulation attracts the EU H317 phrase, and it is also required to carry an associated GHS pictogram. If the sensitizing compound is present below its SCL but above one tenth (1/10) of its SCL, then the coating formulation attracts the EU H208 allergen phrase. No pictogram is required with EU H208. Therefore a consumer is more likely to notice the hazard communication associated with EU H317.
For one member of the isothiazolinone class of preservatives, there is a recommendation to change its specific concentration limit. In March 2016, the Risk Assessment Committee (RAC) of the European Chemicals Agency (ECHA) published an opinion to reduce the SCL, and associated EU H317 trigger concentration, for MIT (2-Methyl-4-isothiazolin-3-one) from 1000 ppm to 15 ppm. The ECHA RAC committee is responsible for preparing the opinion of ECHA on proposals for harmonized classification and labeling. However, the final decision for proposals for harmonized classification and labeling is taken by the European Commission through a committee procedure. So in the case of MIT, while a proposal has been made, a final decision has not yet been reached.
As mentioned above, many of the preservative systems currently selected by coatings formulators within the European Union were selected to meet the challenge of avoiding the EU H208 allergen phrase. Significantly, many of these preservative systems contain MIT. Therefore, if the classification proposal that has been put forward by the RAC committee is approved and therefore adopted by ECHA, then the coating formulator’s challenge of achieving robust preservation while avoiding hazard phrases will become much more difficult.
Preservation – Future?
Given the adverse trends impacting the historically popular in-can preservative active agents, there is likely to be a re-evaluation of antimicrobial active agents from other use patterns. For example, the pyrithione active agents, which were traditionally used as fungicides, are finding increased use as co-biocides for in-can preservation. Use of a co-biocide makes possible a strategy whereby robust preservation is achieved by using a low level of isothiazolinone preservative as a base, and supplementing this base with a sufficient concentration of one of the pyrithione active agents. One benefit of this strategy is that a powerful antimicrobial effect is achieved by combining these two complimentary active substances, for example by combining 1,2-benzisothiazolin-3-one and sodium pyrithione. Pyrithiones target microbial membranes by acting as a chelating agent and disrupting essential ion gradients. Bacteria use these gradients to store energy, and fungi as a source of energy for nutrient transport. BIT is electrophilically active and reacts with microbial enzymes containing thiol groups, thus disrupting a number of vital metabolic (energy) processes.
BIT blends with either zinc or sodium pyrithione represent options to provide robust in-can preservation in many applications without the requirement to declare an EU H208 or EU H317 phrase on the packaging.
In our laboratory we conducted testing to evaluate three potential blend formulations of this type. Formulation #1 was prepared as a solution and it contained 8% sodium pyrithione (NaPT) and 2% benzisothiazolinone (BIT). Formulation # 2 was prepared as a dispersion and it contained 5.5% zinc pyrithione (ZnPT) and 5.5% benzisothiazolinone (BIT).
Formulation #3 was prepared as a solution and it contained 4% sodium pyrithione (NaPT) and 2% benzisothiazolinone (BIT). Note that an in-can preservative with a BIT concentration of 2% can be used up to a dosage of 0.25% without causing the preserved product to attract the EU H208 allergen phrase. Since both formulation #1 and formulation #3 contain 2% BIT, they both have the same 0.25% dosage level trigger for EU H208. Given their higher trigger threshold, these two formulations were evaluated in our challenge tests by preparing a ladder of samples with increasing preservative levels, for example: 0.10%, 0.15%, 0.20%, 0.25%, etc. In contrast, an in-can preservative with a BIT concentration of 5.5% can only be used up to a dosage of 0.09% without causing the preserved product to attract the EU H208 allergen phrase. Therefore, given its higher BIT level, formulation #2 was evaluated in our challenge tests at only the single 0.09% dosage level.
The three preservative formulations were evaluated using an industry-standard repeat insult antimicrobial challenge test. Challenge testing was conducted in a variety of industrial substrates. In setting up these tests, consideration was given to the type of organism most likely to thrive in the individual preserved product. Acidic-preserved products were challenged with yeast and fungi, and alkaline-preserved products were challenged with bacteria. For each type of inoculum, we used a mixture of microbial strains, and the individual strains in the mixture were selected to represent the common spoilage organisms for that type of industrial substrate. The intent in testing a range of substrates was to determine if these three formulations could consistently pass challenge tests at concentrations below their hazard communication trigger concentrations. As shown in Tables 1-3, these three formulations did in fact meet that criterion. Summary results for formulation #1 are shown in Table 1. Summary results for formulation #2 are shown in Table 2. Summary results for formulation #3 are shown in Table 3.
Regulatory trends for preservatives are significantly limiting the options for in-can protection of coatings. When it is desired to create a coating formulation that has relevance for multiple regions, the preservative selection challenge for the formulator becomes particularly acute. In some regions coatings formulations that would otherwise be non-hazardous may attract hazard communication phrases based on their in-can preservative content. This situation already poses a considerable challenge for formulators of water-based coatings and, as additional hazard communication requirements come into force, the difficulty will only increase. In this environment, preservative blends where the pyrithione active agents are used as co-biocides can be welcome new preservation tools for the coating formulator’s toolbox.