National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterJune 2016

Kleinstreuer highlights groundbreaking approaches to safety testing

By Catherine Sprankle
Reprinted from Environmental Factor

NIEHS scientist Nicole Kleinstreuer, Ph.D., highlighted groundbreaking advances in chemical safety testing in an April 26 presentation to about 40 science enthusiasts at The Frontier in Research Triangle Park, North Carolina. Her talk, “Using Computing to Advance Toxicology,” was part of the American Scientist magazine Pizza Lunch lecture and podcast series.

According to Kleinstreuer, deputy director of the National Toxicology Program Interagency Center for the Evaluation of Toxicological Methods (NICEATM), traditional testing methods that use animals to assess potential health effects of chemicals are too slow and expensive to meet current testing needs. She focused on three projects to illustrate methods that can help address the problem of too many chemicals, not enough data.

“Traditional approaches assume you need a whole animal to model the complexity of human toxicity,” explained Kleinstreuer. “But once we understand the biological pathways that lead to toxicity, data from cell-based or biochemical assays can be combined and analyzed using computing methods, to give us models of human toxicity that are better than animals.”

Eliminating animal testing for skin sensitizers

Such an approach can identify skin sensitizers, which are substances that can cause allergic skin reactions. The biochemical processes that lead to such reactions are well understood, so Kleinstreuer and colleagues developed computing methods that make predictions based on measurements of those processes.

She emphasized the practical importance of this advance, saying “In Europe, animal testing was banned several years ago for cosmetics and cosmetics ingredients. The lack of a regulatory nonanimal test to identify skin sensitizers has caused stagnation in new cosmetics product development.” Kleinstreuer and international regulators will meet this fall to develop a plan to put these nonanimal methods into use.

Making an impossible goal achievable

Kleinstreuer and colleagues at the U.S. Environmental Protection Agency (EPA) developed a similar approach for the EPA Endocrine Disruptor Screening Program. The laws that created the program require EPA to screen thousands of chemicals for their potential to interfere with endocrine systems and possibly cause health problems.

Using current methods, testing the chemical universe mandated by the program would require thousands of years and billions of dollars. So Kleinstreuer and colleagues helped develop and validate a faster and cheaper approach, combining data from 18 cell-based or biochemical assays.

The acceptance of this approach by EPA in 2015 was the first time a regulatory agency approved a nonanimal test as an alternative to an animal-based method. “This is groundbreaking,” Kleinstreuer said. “This is where you cheer.”

The Virtual Embryo Project

She described her postdoctoral work at EPA on the Virtual Embryo project as more forward-thinking and speculative. Kleinstreuer developed computer programs to create visual models of normal blood vessel development in human embryos that show disruptions from chemical exposure. The model’s predictions of effects from specific chemicals were confirmed by independent laboratory tests.

Kleinstreuer’s presentation was warmly received by the Frontier audience. Questions addressed practical applications of the new methods. Other comments expressed enthusiasm about the approaches. “It’s so nice to know that the government is actually doing true cutting-edge science,” remarked one attendee.

(Catherine Sprankle is a communications specialist for ILS, the contractor supporting NICEATM.)


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