Pre-Market Testing

Solstice yf

Assessing Product Safety

Honeywell takes safety very seriously. During product development the company submits new substances to extensive testing to determine if and under what conditions a substance can be used safely.

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The goal of toxicity testing is to evaluate the potential hazards of a compound and determine the acceptable exposure levels that will have no lasting adverse or irreversible impact on humans and the environment. This often involves and sometimes requires animal testing. The general approach is to use exposure levels that are sufficiently high to detect any adverse effects. These levels provide guidance on acceptable exposure concentrations using generally accepted safety margins. So it is not surprising when not all test animals survive certain toxicity tests. A comparison between the toxicity end-points for the refrigerant currently in use in automobiles, R-134a, and the new R-1234yf shows no substantial difference between the two products. These tests have followed internationally accepted OECD guidelines. Based on the results of these studies, HFO-1234yf is not toxic.

It is important to make a distinction between acute and chronic (long-term) toxicity. Acute toxicity evaluates the hazard following a one-time exposure to high levels of a compound. It is relevant in cases of incidental or accidental exposure to a substance. This could involve people who have not been trained or are not expected to be exposed to the substance under normally foreseeable conditions of use. The most common reference value used under these instances is the Emergency Response Planning Guidelines (ERPG) which focuses on the acceptable levels that do not result in irreversible or lasting damage. The ERP is also used in Europe. The ERPG-2 for HFO-1234yf is 24,000 parts per million (ppm), which equals 2.4 percent of the substance. For HFO-1234yf, there was no acute toxicity observed, even at concentrations as high as 40 percent.
Chronic toxicity focuses on evaluating the hazard of a compound following repeated exposure to it. These data are used to determine levels, which would not result in irreversible or lasting injury to people who have been trained in handling the substance under foreseeable conditions of use. This is usually expressed as the 8-hour Time Weighted Average (TWA) concentration. The TWA for HFO-1234yf is currently set at 500 ppm, which is a factor 25 times above the generally observed maximum concentration in manufacturing plants, which has been measured at less than 20 ppm, and typically less than 1 ppm.

Honeywell has contracted toxicology studies with leading institutes that follow Good Laboratory Practices (GLP). These institutes are based in the US, Europe, Japan and China and provide specific expertise and world class capabilities.

All the contracted institutes have performed the requested tests under GLP and internationally recognized protocols, in particular the OECD guidelines. The test results have been submitted for review to the national competent authorities.

Most countries have adopted legislation that identifies and controls the hazards of the use of chemical substances. The European Union has the REACH regulation (Registration, Evaluation and Authorisation of Chemical Substances, EU Regulation 1907/2006) and the CLP Regulation (Classification, Labeling and Packaging of chemical substances, EU Regulation 1272/2008). The USA has its Toxic Substances Control Act (TSCA). These laws require producers and importers to prove if and under what circumstances chemical substances can be used safely. They also require them to provide adequate information to users to prevent unsafe use conditions. Under these laws, companies must conduct tests to determine the potential hazards associated with the substances they produce and sell. Companies also need to assess the risks associated with the intended use of their products. They are also required to communicate the risks to the intended users, both via the product labels on the packaging and via Material Safety Data Sheets (MSDSs). These MSDSs summarize the hazards and the risk control measures, especially for professional users and emergency responders such as fire-fighters, physicians and other rescue organizations. The MSDS can be compared to the package insert in any pharmaceutical product sold to consumers. It lists all possible risks and provides guidance to avoid complications or unwanted side effects.

Interpreting Toxicology Results

The interpretation of toxicity test reports requires very specific expertise. Toxicologists undertake comprehensive university-level training, usually with advanced degrees, as well as on-going, on-the-job training that enables them to design and interpret the tests assessing the hazards associated with a specific substance. Usually the results of studies that have a significant relevance for society are published in peer-reviewed authoritative publications. One critical element in the assessment of results is the existence of generally accepted protocols and the availability of reliable reference data and results. Especially in the case of chronic, long-term exposure, it is often very difficult to attribute a certain observed effect to a particular substance. This is the reason why Honeywell appealed the decision of the European Chemicals Agency (EChA) requiring a 90-day test in rabbits because results of such a study, in the absence of a generally accepted protocol and the lack of a body of reference material, (such tests have not been conducted in 20 years) would be meaningless. This view is shared and supported by leading toxicologists. Since rabbits are extremely sensitive to stressful situations, especially to conditions encountered in a 90-day exposure test, any observed effect could be the result of many factors, including those unrelated to the exposure to a test substance. In this context, it must be noted that Honeywell did conduct a 90-day repeated inhalation study in rats, which are much more stress resistant, and for which generally accepted protocols and methodologies exist.

Status of the 28-day Test

The purpose of the 28-day test in rabbits was to evaluate the toxicity in rabbits following repeated exposure. Analysis of tissue samples from the study subjects is still on-going. A final report is expected during the fourth quarter of 2012. Honeywell will continue to update regulators and customers as the information warrants. Once we have conclusive results, we will also communicate to the user communities affected – namely repair and service personnel, OEMs and supply chain — and update our REACH registration.

The results of the toxicity testing are summarized in the MSDS. As noted above, making the body of test reports available to the general public would be an extraordinary step which would not necessarily lead to clarification for the consumer. It would be similar to an individual patient requesting a pharmaceutical company to disclose the full battery of pharmacological test reports for products offered for sale – a demand that is both uncommon and unnecessary. Today, in the vast majority of countries around the world, governments, through their regulatory agencies, assume the responsibility for permitting the sale of safe and effective products. To that end, Honeywell has submitted the full test reports and the expert assessment to the regulatory authorities, including EChA, Japan, Korea and the US EPA, as well as specialist third parties –SAE-CRP, ASHRAE and WEEL Committees, German MAK Committee, and others — and the automotive OEM community –members of ACEA, VDA, JAMA, etc. As noted above, there are regulatory requirements to summarize critical data points in a Chemical Material Safety Data Sheet.

Conducting toxicity tests with reputable external specialized laboratories constitute a substantial investment and the resulting test reports are considered proprietary information. Existing legislation recognizes that such information represents a substantial value and should be protected to prevent free-riders from taking advantage of it for securing their own regulatory approvals. In general, summaries of the study results are available on the websites of the regulatory agencies.