Covance was approached by a client about an older substance originally registered under Notification of New Substances (NONS), but assessed under Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. The client approached Covance after the European Chemicals Agency (ECHA) had issued a draft decision, which requested extensive additional studies. Covance was asked to plan a strategy to address the draft decision, as well as to support the client, as a nominated representative, at a Member State Committee (MSC) meeting to discuss the draft decision.

1. Chemical Services Case Study
REPRESENTING CLIENTS IN FRONT
OF ECHA
Background
Covance was approached by a client about an older substance originally registered under Notification
of New Substances (NONS), but assessed under Registration, Evaluation, Authorization, and Restriction
of Chemicals (REACH) regulation. The client approached Covance after the European Chemicals Agency
(ECHA) had issued a draft decision, which requested extensive additional studies. Covance was asked to plan
a strategy to address the draft decision, as well as to support the client, as a nominated representative, at a
Member State Committee (MSC) meeting to discuss the draft decision.
The Challenges
This situation had multiple challenges, some of which could have been prevented if Covance had been involved
earlier in the process:
▶ Old substance with limited study data and no prior risk assessment data:
The data dossier for the substance had been compiled under previous legislation and, therefore, had some gaps
in the information that was required under REACH. One of the significant gaps related to risk assessment data,
as limited information was available on supply scenarios, use patterns, and potential exposure for the volume of
material being supplied.
▶ ECHA requested additional complex long-term studies:
Given the amount of missing data, especially related to exposure, ECHA requested data on endpoints for prenatal
developmental toxicity, repeated-dose toxicity and environmental toxicity, including long-term aquatic toxicity and
fish bioaccumulation, which were additional to the endpoints submitted in the original testing proposal.
▶ Limited time for a response:
The client had missed the opportunity to engage with ECHA earlier in the decision-making process and only
approached Covance after the draft decision on the testing proposal had been published. This left limited time to
review the data and plan a response.
The Solutions
Covance supported the client through a comprehensive review of the data in the context of the regulatory
requirements and provided technical expertise in front of ECHA.
Covance’s technical experts unpicked the scientific issues at the heart of the problem
Covance took a science-focused view of the problem, exploring the physicochemical properties of the substance
in the context of likely exposure scenarios. Key to this was understanding the hydrolysis profile of the substance;

2. Covance assessed existing data to make a weight-of-evidence argument, which suggested that the substance
would hydrolyze rapidly in water. In this scenario, it was, therefore, important to assess the toxicity of the
hydrolysis products, rather than just the toxicity of the parent test substance.
Covance’s insight into regulatory decision-making supported the creation of an alternative testing
plan to satisfy ECHA
Covance understands that the need to consider animal usage and welfare is inherent in REACH legislation
and, therefore, developed an alternative testing proposal that used a tiered approach to examine the
toxicity of the hydrolysis products. The first step proposed was measuring the n-octanol/water partition
coefficient (log Pow) for each hydrolysis product to predict its potential to bioaccumulate. Higher-tier
testing would only be triggered if a hydrolysis product showed a high potential for bioaccumulation.
This proposal addresses the ECHA concern on toxicity while taking into account the legislative drive to
reduce animal testing.
Covance presented a convincing technical and regulatory case to ECHA
Covance scientists presented their alternative testing proposal and the scientific rationale behind it at a
meeting of the ECHA MSC in Helsinki. The Covance advocacy was judged sound from both a scientific
and regulatory viewpoint, and the MSC accepted the alternative proposal.
Conclusions
Covance saved the client a considerable amount of money and time by devising and advocating a tiered
testing approach built on the science of the substance and aligned with the REACH regulation and ECHA
goals. Covance also took due consideration to minimize animal usage by thoroughly assessing the need for
each endpoint requested by ECHA as part of the decision-making process.
Visit www.covance.com/chemical to find out more.
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