Cassandra Taylor
Regulatory Specialist,
Nexreg Compliance Inc.
Regulatory International
Influences
ECHA and animal testing
Regulatory utility of non-animal test methods for chemical safety assessments in the EU
More than 100,000 people have signed an open letter to
the European Commission and the European Chemicals
Agency (ECHA) demanding an end to animal testing1.
The Registration, Evaluation, Authorization & Restriction of
Chemicals (REACH) regulation mandates that specific information
requirements must be fulfilled in order to place new chemicals
on the market in Europe. If there are gaps in the existing
information for a chemical, testing must be performed. Many
of the higher tier hazard endpoints, such as mutagenicity and
repeated dose toxicity, require testing to be performed on vertebrate
animals. Due to the strict information requirements under
REACH, the EU has established itself in the forefront of testing
for the assessment of chemical hazards.
In November 2017, ECHA published a report on the regulatory
applicability of non-animal approaches under REACH, the Classification,
Labeling & Packaging regulations (CLP) and Biocidal
Products Regulation (BPR)2. The report includes a detailed summary
of the presently available alternatives to animal testing as well
as methods that are currently under development. Some important
aspects that should be considered in the application of non-animal
test methods are described in the report, including the combination
of data for regulatory adaptations. ECHA claims that while
significant progress has been made toward alternatives to animal
testing on lower-tier endpoints such as skin sensitization, the full
replacement of vertebrate testing with non-animal approaches is
not yet foreseeable.
ECHA asserts that they are committed to promoting the development
and use of non-animal approaches. However, they also
maintain that the primary objective of REACH is to assure a high
level of protection to human health and the environment and that
this objective must not be compromised.
For those substances that are produced or imported into Europe
in quantities of less than 100 tonnes per year, the toxicological
information required under REACH is less complex and there are
appropriate in-vitro methods and existing experimental data available.
The primary focus then, are the methods in place for testing
substances produced or imported in quantities greater than 100
tonnes per year, which require more complex data endpoints. New
methodologies that have the potential to provide cruelty-free human
relevant data, such as high throughput assessment methods
that can support alternative approaches, are under development.
Current landscape and test methods
used under REACH
EU chemical legislation authorizes animal testing only as a last
resort; existing data and alternative methods should be used to
fulfill requirements when available. Registrants may only carry out
new vertebrate tests when all other relevant data sources have been
exhausted. The use of non-animal approaches is promoted according
to the 3Rs principle of animal use: “Replacement, Reduction
and Refinement.” Animal tests may be replaced with tests that
use non-animal systems, invertebrate
or early-stage vertebrate species or
other non-animal approaches. Effort
should be made to reduce the number
of animals required to achieve an
objective by maximizing the information
obtained per animal, reducing
the number of animals used in each
test and limiting subsequent testing.
Also, test methods may be refined to
enhance animal wellbeing and cause
minimal pain or distress.
Data sharing is one way that
REACH minimizes the number of
animal tests performed. Companies
that register hazardous chemicals are obliged to jointly submit
information about their hazardous properties to ECHA. In this
way, test results for the same substance can be shared to prevent
the repetition of animal studies. Additionally, there are alternative
methods and approaches that may be applied; existing data from
animal studies can be used to fulfill requirements and the properties
of untested substances may be predicted by comparing them to
chemically similar substances in a technique called read-across.
Under the REACH regulation, requirements for in-vivo studies
(performed in a living organism) have now been replaced by invitro
methods (performed in a controlled environment outside a
living organism, such as in a test tube) for endpoints including serious
eye damage/eye irritation, skin corrosion/irritation and skin
sensitization. Unfortunately, the availability of in-vitro methods for
higher-tier endpoints such as carcinogenicity is still limited. The
information requirements for higher-tier endpoints are more complex,
making the development of direct replacements a challenge.
A more practical solution may be the combination and integration
of various humane test methods into assessment strategies for the
evaluation of complex endpoints.
40 SPRAY March 2018