Hazardous Substance Restrictions …And Why They Are Restricted

Editor’s Note:  The paper on which this article is based was originally presented at the 2017 IEEE International Symposium on Product Safety Engineering in San Jose, CA. It is reprinted here with the gracious permission of the IEEE. Copyright 2019 IEEE.

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This article will offer a basic introduction to material and substance safety from a toxicological point of view. A short review of the regulations that restrict substances will be provided, followed by a description of regulated substances and insight into why they may be restricted at the specific levels given in the standards and regulations.

Product compliance engineers who work with information technology equipment, entertainment equipment and home appliances are familiar with substance restriction regulations that primarily address the end of life of electrical and electronic equipment. That is, restricting hazardous substances so that they do not end up in the water or air after the product ends up in a landfill or incinerator. These limits are often much higher than a medical device or toy manufacturer would want for a patient or consumer to be exposed. This paper is intended for the manufacturers of the product categories listed above.

Paracelsus, a 16th Century Swiss German philosopher and scientist who is largely regarded the founder of toxicology, is credited with the quote “What is there that is not a poison? All things are poison and nothing without poison. Solely the dose determines the thing that is not a poison.” The modern variant of this, familiar to all toxicologists is “the dose determines the poison.” The phrase is so often repeated as it is fundamental to what toxicologists need to understand, specifically, 1) what are the adverse effects observed when exposed to a particular substance, and importantly, 2) what is the dose, and exposure conditions, required to produce that effect seen?

When working in a regulated field, it is especially important to understand the difference between hazard and risk. A hazard is a chemical’s intrinsic ability to cause adverse effects, whereas, risk is the probability that such effects will occur in the various applications in which the chemical will be used (exposure scenarios). To drive this distinction home, as an example, consider the sun and its potentially damaging UV rays as a hazard. The sun has the potential to cause severe burns if a person (user) is exposed long enough on a sunny day. However, now think of this same hazard, the sun, but the user is under a huge umbrella in the shade with copious amounts of sunscreen applied. In this scenario, the risk to the user for developing burns is quite low, even though the same hazard is still present.

In terms of regulations, some aim to identify hazards and ensure that they are properly labeled so users know how to appropriately handle the substance and what personal protective equipment and precautions should be taken. Whereas other regulations which are risk-based will look at the hazard and also consider the conditions and context of use to determine which steps, if any, should be taken. Understanding the principles, specifically whether it relates to a hazard or risk, on which a regulation is based will aid in understanding why some chemicals may need classification in one scenario but not another.

Regulations

Substance restrictions in two basic categories will be discussed. The first are restrictions to limit release into the environment, usually at the end of life of the product when it is disposed of. The second are restrictions to limit direct exposure to individuals using or handling the product. Toy and medical device regulations and standards are examples that address this aspect.

There is a third category, restrictions of controversial substances. These are substances that do not necessarily have a scientific consensus as to the level of hazard they present at concentrations used by industry. An example is Bisphenol A (BPA). While some of the same regulations or standards in the first two categories of regulation may address controversial substances, companies are often under pressure to completely eliminate the substances so that even trace amounts are not detectable. A company will often restrict the use of these substances even when regulations do not or set limits much lower than regulations permit in order to meet consumer preferences.

RoHS

The Restriction of the use Of certain Hazardous Substances in electrical and electronic equipment (RoHS), European Directive 2011/65/EU[1] amended by EU 2015/863 (RoHS2) [2], limits ten substances. This list includes four heavy metals, two brominated flame retardants, and four phthalates. It applies to electrical and electronic products. Many similar regulations exist throughout the world, for example, China Administrative Measures for the Restriction of the Use of Hazardous Substances in Electrical and Electronic Products (China RoHS2).

Limits are set at 1000 ppm (by weight) for all substances except for cadmium, which is set at 100 ppm at the homogenous level. Homogeneous material means a component or material that cannot be mechanically disjointed into different materials by unscrewing, cutting, crushing, grinding, abrasive processes and similar procedures. The purpose is to limit these harmful substances from being released into the environment after the product is discarded.

REACH

The Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) is a complete re‑evaluation of chemicals used in the European Union (EU). REACH Regulation (EC) No 1907/2006[3] is a broad piece of legislation that covers all industries in the EU and products, materials, intermediates and substances manufactured in or imported into the EU. Chemicals of concern are identified and added to Annex XIV and referred to as Substances of Very High Concern (SVHC). Its purpose is to improve the protection of human health and the environment from the risks that can be posed by chemicals. It also promotes alternative methods for the hazard assessment of substances in order to reduce the number of tests on animals.

There are two lists within REACH. Candidate List chemicals are subject to protocols such as restricting amounts in products, manufacturing processes, consumer uses or emissions and end of life releases. These are known as REACH regulation threshold amounts. Authorization List chemicals require authorization by the EU before a company is allowed to use them in manufacturing. At the end of 2016, there were 31 SVHCs in the Authorization List and 169 SVHCs in the Candidate List.

Unless otherwise noted in Annex XVII, the concentration limit is 0.1% weight by weight (0.1% of substance total in total article weight). An article means an object which during production is given a special shape, surface or design which determines its function to a greater degree than does its chemical composition. Articles which are present in complex products (i.e., products composed of several articles) also must meet the concentration limit, as long as these articles keep a special shape, surface or design or as long as they do not become waste.

The list of SVHCs is broad and impacts many industries. A substance may be proposed as an SVHC if it is carcinogenic, mutagenic, toxic for reproduction, persistent bioaccumulative and toxic, very persistent and very bioaccumulative, or if there is scientific evidence of probably serious effects to human health or the environment that give rise to an equivalent level of concern.

Product manufacturers are primarily concerned with Article 33. This Article requires companies that sell articles which contain an SVHC at a concentration greater than the limit to provide sufficient information to allow the safe use of the product.

Unlike RoHS, REACH does not have mirror regulations world-wide. There are some regulations with the same intent, for example the U.S. Toxic Substances Control Act (TSCA) overhauled by the Frank R. Lautenberg Chemical Safety for the 21st Century Act[4].

Safety of Toys

In the U.S., the Consumer Product Safety Commission (CPSC) is charged with protecting the public from unreasonable risks of injury or death. The CPSC uses the federal toy safety standard, ASTM F963-11[5] to protect children aged 12 and under. ASTM F963 is a comprehensive standard that addresses many hazards related to toys. Besides physical and mechanical properties, the standard also addresses limits for substances that are toxic, corrosive, an irritant, sensitizer or pressure generating, and radioactive, flammable, and combustible materials. ASTM F963 has limits for eight heavy metals that vary depending on the metal type. Additionally, six types of phthalates are currently banned for use in children’s toys and certain child care articles according to the Consumer Product Safety Improvement Act of 2008[6].

In Europe, the EN71 series of standards covers toy safety. EN71-3[7] contains requirements for limiting heavy metals to minimize children’s exposure to certain potentially toxic elements. The standard limits 19 metals from toy materials and parts of toys. The limits vary based on the metal type and material application. The EU Toy Safety Directive 2009/48/EC[8] has additional restrictions for substances classified as carcinogenic, mutagenic or toxic for reproduction (CMRs). REACH applies to toys as well, and RoHS applies to toys with electrical or electronic components.

Many country and regional standards and regulations use either ASTM F963 or EN71-3 as a basis for their requirements.

Biocompatibility Testing

Protection of humans from materials and devices is commonly verified by standards like the ISO 10993 series for the biologic evaluation of medical devices[9]. ISO 10993 is made up of many parts that address a range of potential biological hazards. This includes both short and long-term effects. Examples of short-term effects are acute toxicity, and irritation to skin, eyes, etc. Long-term effects include chronic toxic effects, genotoxicity and carcinogenicity.

Biocompatibility evaluations may involve analysis as well as in vitro (i.e., cell cultures), in vivo (i.e., whole organisms-human or animal) testing, in silico (computer simulation or modeling), or read-across (use of relevant information from analogous substances). The evaluation takes into account the chemical composition of the materials, including conditions of exposure and the nature, degree, frequency and duration of exposure to the body. The thresholds of concern and margin of safety are part of this evaluation.

The FDA lists ISO 10993 as a consensus standard for medical devices[10]. Other regulatory agencies and some medical device test standards reference ISO 10993 as well.

Substances

In this section, some example substance groups will be presented and discussed. This is not an exhaustive list but rather a list of the most commonly restricted substances.

Heavy Metals

“Heavy metals” are defined as elements that form cationic ions upon ionization and generally have high atomic weights, a density > 5g/cm² relative to water. Heavy metals are also classically associated with toxicity that is inducible at low levels of exposure, which can push the definition of heavy metals to include metalloids as well (Tchounwou, 2012)[27]. The study of metal toxicity is intrinsically linked to the study of toxicology just as metal use has been critical to the development of human civilization (Liu, 2007)[24]. The primary benefit of the study of the toxicity of heavy metals has been the realization that proper restrictions to these toxic metals has led to reduced human health concerns.

With the exception of a few metals, consumers and workers are essentially exposed to the same chemicals through industrial, agricultural, domestic and technological applications (Tchounwou, 2012)[27]. The level of concern, therefore, depends on the exposure. This is where many of the regulatory bodies have set safety limits which provide significant margins of exposure designed to protect human health while taking into account multiple sources of heavy metals including food sources as well as industrial sources (Järup, 2003)[18].

Analysis of heavy metals is generally required due to their intrinsic hazard, their bioavailability and their proportion of substance that enters into the system. Bioavailability of heavy metals is the chief concern due to their potential varied effects. The main heavy metals of concern for human safety are lead, cadmium, mercury and arsenic, which in particular can have long-lasting effects on the brain (Järup, 2003; Karri, Schuhmacher, & Kumar, 2016)[18][20]. Below we discuss these 4 main metals of concern in brief.

Lead

Lead is one of the first metals that was excavated from the Earth’s crust for human use (Assi, Hezmee, Haron, Sabri, & Rajion, 2016)[13]. Historically, the initiation of proper occupational safety controls has been associated with preventing lead toxicity (Lippmann, 1989)[23]. The seminal work of Alice Hamilton in the development of practical and safe practices to reduce the high mortality rates due to industrial poisoning in the lead and lead-associated enamelware, rubber production, painting trades and explosions industries were critical to establishment of safe practices (Ginsberg, 2002)[18]. Her work led directly to the formation of OSHA.

Target organs of lead include the nervous system, hematological systems and renal system. Primarily, lead exposure can be from natural and manmade sources including from pipes, as a stabilizer in plastics, and as impurities in drinking water. Lead has been restricted from use in paints and toys as well, due to the special neurological sensitivity that children have to lead (Lippmann, 1989)[23]. The U.S. EPA and the Centers for Disease Control and Prevention (CDC) have agreed that there is no known safe level for lead in children’s blood. Some of the negative impacts of lead on adolescent development include lowering verbal IQ, decreased mental development and reduced physical sizes (Lippmann, 1989; EPA)[23][16]. The EU has restricted the use of lead to 0.05% by weight in jewelry articles unless the migration rate can be demonstrated to be below 0.05 mg/cm²/hr (Commission Regulation (EU) No 836/2012)[12].

Cadmium

Cadmium is a commonly used metal in rechargeable batteries, alloys, solar cells, plastic stabilizers and in pigments. Consumers are mainly exposed to cadmium through plastics (Agency, 2015)[12]. Cadmium is highly toxic and a known carcinogen. Cadmium targets multiple organ systems including the cardiovascular, renal, neurological, reproductive and respiratory systems. Ionic cadmium is considered the most hazardous form. Renal damage from chronic exposure to cadmium is based on exceeding urinary threshold concentration, signaling that the body’s ability to detoxify cadmium has been exceeded. In addition, cadmium is classified as a CMR.

Based on these toxic effects, regulatory bodies have defined usages on cadmium. For example, EU restrictions on cadmium include its uses in pigments, in paints, as stabilizers in finished products manufactured from polymers and copolymers of vinyl chloride, and cadmium plating application. An accepted safe limit of use known as a derived no-effect level (DNEL) has been established for cadmium of 1 µg/kg for non-carcinogenic effects; however, there is some questions raised about the sufficiency of the DNEL with regard to potential leaching exposures. The EU has established a REACH concentration limit of 0.01% by weight in plastic material.

Mercury

Mercury is available in three forms, inorganic, organic mercury and elemental mercury. Mercury, a classic neurotoxicant, has been known to induce toxic effects in the central nervous system, peripheral nervous system, skin and renal systems. Mercury’s target organ for toxicity is dependent on its physical form with inorganic mercury primarily affecting the kidney, digestive system and the skin; organic mercury affecting the nervous system with increased susceptibility for fetuses; and elemental mercury which can adversely affect the lungs, kidneys and skin.

Mercury is prohibited for use in EU in such products as fever thermometers, barometers, hygrometers and other types of measuring devices. Sources of mercury include methylmercury ingested from sea food, which has an increased hazard as it passes through the placenta and can induce developmental abnormalities to the developing fetus (CDC, 2009)[15]. Elemental mercury can be absorbed from novelty jewelry and older thermometers. Inorganic mercury exposure is generally limited to people who work with inorganic mercury compounds or from burning of fossil fuels.

Arsenic

Arsenic (a metalloid) is present in diet and drinking water, from activities including volcanic eruptions, contamination due to mining and smelting ore, and used in pesticides and medicines (Sattar, 2016)[26]. Typical environmental arsenic exposure occurs from arsenic-contaminated drinking water (Jie Lu, 2011)[19]. Arsenic toxicity is dependent upon its oxidation state and its mobility within the body with inorganic arsenite (As+3), arsenate (As+5), and arsenide (As-3) more hazardous than organo-arsenic (e.g., methylarsonate and dimethylarsinate) forms (Sattar, 2016)[27].

Safety limits for arsenic in work places have been set by the U.S Occupational Safety and Health Administration (OSHA) at less than 10 micrograms per cubic meter of air over any eight hour period per week. Arsenic regulations have been established by the U.S. Environmental Protection Agency (EPA) for drinking water (10 ppb) and U.S. Food and Drug Administration (FDA) for food (0.5-2 ppm), respectively. In 2016, the FDA proposed a lower limit of 100 ppb for inorganic arsenic in infant rice cereal. Many countries have adopted the ASTM F963 or EN71-3 standards for arsenic in toys which are 25 ppm or 3.8 ppm, respectively.

Polybrominated Flame Retardants

The use of brominated flame retardants (BFR) to prevent fire hazards had been increasing since the 1970s as a result of its usage in electronic devices such as computers and televisions and its use in epoxy resins, polycarbonate polyesters, and carpets and textiles (Fromme, Becher, Hilger, & Volkel, 2016) (Prevedouros, Jones, & Sweetman, 2004)[17][25]. Beginning in 2004, restrictions on the by weight presence of specific BFRs (i.e., penta-, octa-, and decabrominated diphenyl esters) had been enacted across the EU. Another BFR of concern, hexabromocyclododecane (HBCD), is under increased scrutiny by the EU under REACH. The U.S. has also supported this restriction with 10 states banning both penta- and octa- brominated diphenyl esters, and with U.S. companies phasing out the use and production of BFRs with a stated goal of complete cessation as of 2012 (Fromme, Becher, Hilger, & Volkel, 2016)[17]. The concern with BFRs (and PBDEs) is associated with persistence, bioaccumulation and global distribution in the environment and in human tissues.

Phthalates

Phthalates, diesters of 1,2-benezendicarboxylic acid (phthalic acid), are a widely used family of industrial chemicals which plasticize material. Well-known phthalates including Di(2-ethylhexyl)phthalate (DEHP), have been detected ubiquitously in the environment and at low concentrations in human tissues (Kay, Bloom, & Foster, 2014)[22]. Phthalates are able to migrate from plastic products depending on temperature and pH changes (Katsikantami, et al., 2016)[21]. Urinary levels of phthalates metabolites have been detected in adult populations in Europe (209 µg/L), U.S. (199.70 µg/L), and Asia (125.25 µg/L) (Katsikantami, et al., 2016)[21]. In utero exposure has also been documented by detection of phthalate monoesters in the amniotic fluid, suggesting movement through the placenta, which can affect the fetus (Katsikantami, et al., 2016)[21]. In addition, exposure in human milk has been detected, though at lower levels than observed in the urine.

The full risk remains unclear. However, correlations between early life phthalate exposure and pediatric health outcomes as well as negative human reproductive effects have been suggested (Braun, Sathyanarayana, & Hauser, 2013; Martine-Arguelles, D.B.; Campiolo, ; Culty, M.; Zirkin, B.R.; Papadopoulos, V., 2013)[14][11]. Evidence in animal studies suggests that fetal exposure to DEHP can lead to endocrine disruption. These reports have also stirred media and public attention, leading to regulations and recommendation for the reduction and banning of the use of specific phthalates. In the U.S., the Consumer Product Safety Improvement Act of 2008, banned the use of DEHP and other phthalates in children’s toys and child care products (Braun, Sathyanarayana, & Hauser, 2013)[14]. Phthalates have also been classified as CMRs under REACH due to the suspicion that they disrupt hormones and alter normal reproductive function..

PAHs

Polycyclic aromatic hydrocarbons (PAHs) are a large group (>100) of structurally similar compounds that are known to cause cancer. The main source of PAHs is combustion of biomass and fossil fuels through the incomplete burning of carbon-containing materials (Singh, Gadi, Mandal, Saud, Saxena, & Sharma, 2013)[28]. PAHs are found in consumer products such as rubber and plastic components of toys, child care articles, clothing, sports equipment and household utensils, etc.

The European Commission has set safety limits for PAHs at 0.5 ppm for toys and child care articles and 1.0 ppm for all other articles as of 2015. The maximum contaminant level set by the U.S. EPA for contamination in drinking water is 0.2 ppb. These limits have been set to protect human health against the CMR effects of PAHs. Associated tumors have been noted in the lung, skin, and bladder associated with occupational exposure to PAHs, with both IARC and the U.S. EPA classifying many PAHs as possibly or probably carcinogenic.

Chlorinated Paraffins

Chlorinated paraffins (CPs) are complex mixtures of polychlorinated n-alkanes. CPs are often grouped according to the length of the carbon chain present in their structure. Those with average carbon chain lengths of 10–13 carbons (C10–13) are referred to as short-chain chlorinated paraffins (SCCPs). C14–20 chlorinated paraffins are categorized as medium-chain paraffins, while C20–30 chlorinated paraffins are referred to as long-chain paraffins[28]. Chlorinated paraffins are named according to their paraffin chain length and degree to which they are chlorinated.

The percent chlorination found in commercial CPs lies between 10 to 72 percent[28]. These compounds have been used as lubricant additives in the metal working industry, as flame retardants in commercial furniture, and also have found particular use in automotive upholstery. CPs can contain contaminants – some which unavoidably occur through the manufacturing process, like alkenes and isoparaffins and others that are added as stabilizers, like epoxidated soybean oils, pentaerythritol, organometallic tin compounds, lead oxide and cadmium compounds[28][29]. Since chlorinated paraffins can differ in their chlorine content, size and trace contaminants, ideally each specific chlorinated paraffin should be assessed for its individual risk[28].

CPs are categorized as International Agency for Research on Cancer (IARC) category 2B – possibly carcinogenic to humans. SCCPs are categorized as persistent and also have a high bioaccumulation potential[30]. Aside from SCCPs, there are environmental persistence concerns for all size chlorinated paraffins. Environmental concerns appear to drive regulation for CPs, not necessarily human health concerns. Due to qualities that can have an impact on the environment, there have been efforts to reduce the use of chlorinated paraffins

Tris(2-chloroethylene)phosphate

Tris(2-chloroethyl)phosphate (TCEP) is an alkyl phosphate ester compound. TCEP has been used as a flame-retardant plasticizer and viscosity regulator in polymers such as polyurethanes, polyester resins, and polyacrylates. It has been used in roofing insulation in the building industry as well as a in furniture and textiles[30]. The brain, kidney and liver have been shown to be the main target organs of toxicity in short and long-term toxicological studies in experimental animals. TCEP has been shown to be carcinogenic in animals; however the relevance to humans is unclear. The Scientific Committee on Environmental and Health Risks (SHER) opinion stated that, due to the lack of knowledge of the possible mode of action but considering all available data, the relevance to humans of renal and hepatic tumors cannot be excluded. TCEP also has been shown to be a reproductive toxicant to animals. In the toy industry, there have been concerns of exposure of TCEP to children – with special concerns for children below 3 due to the mouthing behavior of this age group. Regulations have been enacted to prohibit or limit this substance from toys in various geographies.

Conclusion

Determining substance limits based on toxicological effects is a complex process and may go well beyond regulatory limits. The requirements for substance restrictions are influenced by the toxicology, product use, end of life handling and consumer perception.

Many product compliance engineers, designers and managers are only aware of the regulatory limits on substances and do not have toxicologists available to explain the reasons why certain substances are restricted. Understanding the effect of these substances on the human body and environment, and the dose at which these effects occur, can help in determining a margin of safety for many types of products.

Acknowledgement

The authors deeply appreciate the contributions of Kristian Fried. His thorough review and comments have helped strengthen the paper.

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Dan Roman is a product compliance manager and iNARTE Certified Product Safety Engineer engaged in design and certification aspects of international safety, EMC, telecom, wireless, and product ecology, and can be reached at dan.roman@ieee.org. Craig Harvey is a Board-Certified Toxicologist registered in the USA and Europe who works on process corrections and In Silico Toxicology. He can be reached at craig_harvey@colpal.com. Lauren Hutchison is an experienced Board-Certified Toxicologist with 10 years in the Consumer Products Industry, and can be reached at lauren_hutchison@colpal.com.