Photo: E. Hill, IIVS.

InVitro+Jobs: How realistic is it to definitely end animal testing by 2035?

Dr. Hill: I believe that ending animal testing by 2035 is an ambitious plan – but sometimes an ambitious goal is what is needed to create significant change. In order to achieve their goal, the EPA will necessarily have to move away from a 1 to 1 validation and replacement of animal models and embrace the mechanistic information provided by NAMs. As long as we compare the new methods to inherently variable animal tests we will never move forward. We have experienced this even for the “simple” endpoints of eye and skin irritation. In addition, without the program being led (or with heavy involvement from EPA) then companies don’t have the assurance that NAMs will be accepted.

For the American Environmental Protection Agency (EPA), the reduction of animal experiments in toxicology has priority: According to a new guideline, all involved parties must ensure that animal experiments with mammals for the safety assessment of chemicals are first reduced by 30% by 2025 and then ended by 2035. Applications for authorisation for chemicals must be rejected if they are related to mammalian studies, exceptions require the explicit permission of the EPA administration as from 2035.
The original memorandum can be found here: https://www.epa.gov/sites/production/files/2019-09/image2019-09-09-231249.txt

InVitro+Jobs: How do you assess the situation?

Dr. Hill: It is important to point out that, from my understanding, the EPA is not banning the submission of animal studies by industry. It is not always the case that NAMs are less expensive – especially when you have to run several in vitro tests to arrive at a conclusion. A good example is the 3 validated tests for skin sensitization – when all 3 tests have to be conducted it can be nearly double the cost of the animal (LLNA) test.  Therefore industry may choose to keep submitting the animal tests to the EPA – especially if they have to submit those data to countries that don’t accept data from NAMs.

In addition, it is difficult for me to judge the magnitude of the reduction in testing. The memo states that by 2035 the EPA will completely stop “supporting” such studies on mammals which indicates a reduction in their own testing.  I do not know how many animal tests the EPA runs itself each year.   I also don’t know how many of the tests are conducted in fish, birds or amphibians which are exempt from this memo. Even with the commitment to completely stop the studies conducted by the EPA, they have included the caveat that those studies can still be carried out with administrator approval.

With all of the challenges, we at IIVS welcome the opportunity to work with industry, the EPA and NGOs to develop appropriate non-animal testing schemes. It also allows the agency to take a step back and decide what information they really need and use – great reductions are already underway by waiving some animal tests under certain conditions.


InVitro+Jobs: According to our information, there are no procedures in the field of reproductive toxicology: Is it foreseeable that these missing methods will have been developed by then? What indications exist for this supposition?

Dr. Hill: We are struggling to identify robust tests or testing strategies that meet EPA needs even for acute measures of eye irritation and skin irritation. Obviously it will be much harder to meet their needs for chronic exposures or systemic effects. I think if the EPA can clearly define what information they require it may be possible to provide them with mechanistic information without the use of live animals, however, it takes time to develop these complex systems and build confidence in their results.
We might see a period of time when data from in vivo tests and NAMs are submitted in parallel to initially evaluate whether the new methods provide adequate scientific information for decision making, prior to the implementation of promising NAMs.

InVitro+Jobs: For other endpoints such as long-term toxicology or inhalation toxicity, there are already replacement procedures that have not been recognized. Are there new developments that there is recognition after all, or are there new, meaningful developments?

Dr. Hill: There is a lot of work going on in the area of inhalation toxicology especially for other agencies such as the US FDA’s Center for Tobacco Products. Here we see the same issues where the regulatory community is more familiar, and therefore more comfortable, with the traditional animal models. It takes time to understand their data requirements and develop suitable models.

InVitro+Jobs: Thank you for the interview.