Green chemistry, polymers of low concern, and animal testing and welfare

Regulatory agencies place some types of polymeric compounds (i.e. polymers of low concern, PLCs) in an exempt category for specific types of product registration testing. Though the time and cost benefits of reduced regulatory requirements for PLCs are clear, an equally important aspect for PLCs relates to animal testing and welfare. PLCs are recognized as presenting a de minimis risk to human health and the environment and significantly reduce, or even eliminate, the number of experimental animals needed for evaluating a substance’s safety. Therefore, it is clear that industries should be encouraged to focus their research and development activities on developing polymeric replacement molecules, whenever possible, which meet the regulatory requirements of PLCs.

In June 1997, the U.S. Environmental Protection Agency (EPA) issued its Polymer Exemption Guidance Manual, which modified the original 1984 polymer exemption rule under the U.S. Toxic Substances Control Act (TSCA) (EPA 1997). After the U.S. EPA had reviewed 10,000 polymers under the standard pre-manufacturing notification and 2000 polymer exemption notices, the Agency identified specific molecular weight and fraction criteria for polymers that “… were most unlikely to present an unreasonable risk of injury to human health or the environment” (EPA 1997). Additional criteria exist in order to meet the U.S. EPA’s polymer exemption, including, for example, that the polymer must not contain >0.2 wt% of specific elements (e.g. iron, nickel, copper, etc.) or degrade, decompose, or depolymerize (EPA 1995).

For polymers that meet the U.S. EPA’s exemption criteria, no experimental testing on animals is required. This approach is not, however, unique to the United States. For example, Australia, Canada, China, the European Union, New Zealand, the Philippines, and South Korea have similar exemptions for PLCs.

Some researchers have noted that a global registration for non-polymeric molecules takes ~2 years to complete (Louwen and Stedeford 2011). This statement fails, however, to appreciate the number of animals used during that time period, along with additional testing that may be required. For example, the general animal testing requirements in the European Union for non-polymeric molecules manufactured or imported in quantities of 10 tons, but <100 tons, per year include:

1. Repeated dose 28-day oral toxicity study in rodents (40 animals; five males and five females per group, with at least three treatment groups and a control) (OECD 2008); and

2. Reproductive/developmental toxicity screening test (~192 animals; 10 males and 10 females per group, with at least three treatment groups and a control. Total animals assumes eight pregnant females per group with an average litter size of 14 pups) (OECD 1995; Parker 2006); or

3. Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (192 animals; 10 males and 10 females per group, with at least three treatment groups and a control. Total animals assume eight pregnant females per group with an average litter size of 14 pups) (OECD 1996; Parker 2006).

Therefore, registering a non-polymeric molecule requires, at a minimum, the use of over 200 animals in a lower tonnage ban. For higher volume molecules, the number of animals required may easily exceed 1000.

In 2007, the U.S. National Research Council’s Committee on Toxicity Testing and Assessment of Environmental Agents published a document titled “Toxicity Testing in the 21st Century: A Vision and a Strategy” (NRC 2007). The committee envisioned an ultimate testing strategy that would eliminate the need for using animals in toxicology studies; however, they noted that a more realistic testing paradigm over the next 10 to 20 years would require some animal testing. Due to the various limitations with implementing non-animal testing strategies, it seems appropriate that industries should focus their research activities on developing polymeric replacement molecules, whenever possible. Such a strategy would not only align their interests with the U.S. NRC’s ultimate vision for non-animal toxicity testing, but also result in the development of safer molecules.

Notwithstanding the above statements, it would be remiss to overlook the importance of the technical challenges that manufacturers face when developing newer and safer chemistries. Though the safety of chemicals is a fundamental concern, manufacturers are also required to ensure that specific technical and performance standards are met when developing new chemicals. In many instances, it might not be possible to develop PLCs, which meet or exceed these standards when compared with existing or new small molecules.

In conclusion, the global movement to develop “greener,” “safer” molecules and to reduce the need for using animals in experimental safety evaluations may be achieved with polymeric replacement molecules. Specific types of polymers are recognized internationally as substances that do not present an appreciable risk of injury to human health or the environment. Therefore, industries should evaluate their portfolios to determine those substances with human health or environmental concerns, which could eventually be replaced with PLCs. A decision in this direction will aid with developing safer molecules and eliminating the use of experimental animals in product development and registration.

Declaration of interest

None to declare.