Estimating Properties Of New Chemicals

Physical and chemical properties of a compound are keys to understanding how it may move through the environment. These properties inform the Environmental Protection Agency as it reviews notices about new chemicals that companies plan to commercialize.

But what does EPA do when it has little or no information on the physical or chemical properties of a new compound? By law, the agency has 90 days after receiving paperwork, called a premanufacture notice, to examine information provided and, if deemed necessary, take regulatory action controlling the chemical to protect human health and the environment.

EPA does this by using specialized software that predicts physical-chemical properties, such as water solubility and melting and boiling points, based on the structure of a compound. EPA uses this cluster of programs, dubbed the Estimation Program Interface (EPI) Suite, to help determine whether and how people and the environment will be exposed to the substance.

EPA recently asked a group of scientists from outside the agency, convened under the aegis of the agency's Science Advisory Board (SAB), to scrutinize the effectiveness of EPI Suite. At a meeting on March 7-9, the reviewers generally gave the software good marks and offered some recommendations for improving it, especially so it can be used to evaluate the growing number of new nanomaterials. The software can't currently be used for nanomaterials.

EPI Suite is essential to the agency's review of new chemicals before they go on the market. EPA relies on data about a chemical's properties, whether measured or estimated, to evaluate whether the substance will dissolve in water or exist as a vapor at indoor temperatures. For instance, EPA uses the vapor pressure of a compound to estimate workers' and consumers' exposure to the chemical during manufacturing and use.

Meanwhile, the rates of a chemical's degradation in water, air, and anaerobic conditions, as well as its Henry's law constant and organic carbon sorption coefficient, all factor into predictions of how well wastewater treatment plants can remove the chemical from effluent. Degradation rates also give EPA an idea of how long the substance may persist in the environment. The agency uses these data to estimate exposure of people and the environment to the chemical, and to help it determine other properties about the substance's interaction with the environment, such as its potential to deplete stratospheric ozone or act as a greenhouse gas.

Using both the results of EPI Suite and the compound's hazard potential, which is commonly calculated from structure-activity relationships, EPA regulators determine whether to delay a company from starting commercial production of a new chemical by requiring the firm to conduct additional laboratory tests on the substance.

Separate from this decision, the agency may require workers handling the chemical to don protective equipment, which can range from gloves for a compound that potentially could irritate the skin to air-supplied respirators for an acutely toxic substance. In addition, EPA can restrict the uses of the new chemical. This restriction provides an avenue for a company to make a new compound that, for example, can be used safely in a controlled industrial setting but may persist in the environment or could pose a health risk if blended into a consumer product.

EPA places some regulatory restrictions on 5 to 10% of the approximately 2,000 new commercial chemicals for which it receives premanufacture notices each year, Cathy Fehrenbacher, chief of the Exposure Assessment Branch in EPA's Office of Pollution Prevention & Toxics, told the review panel. She stressed, however, that EPA does not base these decisions solely on the results generated by EPI Suite. The agency also includes other factors such as chemical hazard information, she said.

If EPA restricts human exposure to a chemical on the basis of physical-chemical property estimates of EPI Suite, the manufacturer of the substance does have some recourse. The company can provide the agency with laboratory data for properties such as the chemical's octanol-water partition coefficient or Henry's law constant. If the submitted values indicate that the agency's estimates led to overly protective controls, EPA is likely to lift the restrictions.

EPI Suite was developed by a private company, Syracuse Research Corp., for EPA in the 1990s. EPA now has sole ownership of the software and makes it publicly available. It is used widely outside of EPA, especially by industry and academic researchers around the world, according to the agency.

Robert Boethling, an EPA scientist who works with EPI Suite, told the review panel that data being submitted by industry as part of the voluntary effort to provide basic information on high-production-volume substances sometimes include physical-chemical property information that companies have derived through the use of EPI Suite.

The review committee praised EPA for making this unique tool available to the public and noted that it is easily used. The panel members agreed that EPA uses EPI Suite appropriately and broadly to screen new chemicals to determine the potential exposure of people or the environment when measured data are not available.

"EPI Suite is a very valuable tool," said Michael J. McFarland, chairman of the SAB panel reviewing the software. McFarland is associate professor of civil and environmental engineering at Utah State University.

The results produced by EPI Suite are usually accurate within an order of magnitude, the committee said. Because it is used as a screening tool that flags chemicals for further investigation, EPI Suite does not need—and is not expected—to be more accurate, the panel said.

The panel said, however, that EPA needs to upgrade the software as necessary to maintain state-of-the-art methods for estimating chemical properties. In addition, EPA should incorporate more data into EPI Suite so the software can be used for polymers, organometallics, and nanomaterials.

Nanoparticles are "an important class of emerging contaminants," and EPA needs tools to screen them, McFarland said.

The review committee members said they would urge EPA Administrator Stephen L. Johnson to provide additional funds and personnel to maintain and improve the software. The slice of the agency's budget for EPI Suite efforts has been steady or declining over the past several years, according to agency officials, while the workload has increased. Allocation of EPA resources for maintaining, updating, and improving EPI Suite is not commensurate to the value of the tool inside and outside of the agency, said panel member Thomas F. Parkerton of ExxonMobil Biomedical Sciences.

Though EPI Suite's home is within EPA, the software has regulatory implications beyond the agency's scrutiny of new chemicals. Pollution control programs at the agency sometimes use EPI Suite. And regulators outside of EPA use it, too.

On the federal level, the Food & Drug Administration employs EPI Suite to a limited degree. "We use it to see if it raises any flag, if actual testing of a food additive is needed," said Layla Batarseh, supervisor of the environmental review group at FDA's Office of Food Additive Safety, in a letter to SAB. Meanwhile, some state and local governments in the U.S. use EPI Suite, as do regulators in some other countries.

The review panel also suggested expanding the universe of EPI Suite users.

Developing countries could use the software as part of their implementation of the new global agreement on chemicals management, said review panel member Hans Sanderson, director of environmental safety, international, and regulatory affairs at the Soap & Detergent Association. That new accord, the Strategic Approach to International Chemicals Management, was adopted by governments in February.

The EPI Suite review panel is expected to issue its final report to the EPA administrator later this month.