2019.05.07_CCO.p14_NCDEQResponsesToLaboratoryQuestions-CharlesRiver

251 Ballardvale Street, Wilmington, MA 01887 • 781.222.6000 • Fax [phone] • www.criver.com

May 7, 2019

Shawn Gannon, Ph.D., DABT
Senior Toxicologist, Toxicology and Risk Assessment (TRAC),
Product Support and Sustainability Center
The Chemours Company
1007 Market Street
Wilmington, DE 19899

To Whom It May Concern:

Charles River Laboratories is pleased to submit input corresponding to the State of North
Carolina’s inquiries as follows:
1) Provide a narrative descriptions of each lab’s experience in the type of toxicity assays to
be provided to Chemours

Charles River Ashland (formerly known as WIL Research) is located in Ashland, OH and
has been performing nonclinical safety testing for Sponsors for over 40 years. These
tests cover a wide variety of endpoints including, but not limited to, general toxicology,
immunotoxicology, developmental and reproductive toxicology, neurotoxicology, genetic
toxicology, and safety pharmacology, and have been performed through many routes of
administration (intravenous, oral gavage, dietary, subcutaneous, inhalation, etc.). The
table below illustrates some of the studies we have performed in the last 5 years via the
oral route (gavage and dietary). For each of these studies, appropriate range-finding
studies of various lengths (5-day, 7-day, 2-week, etc.) would also have been performed.
Selected Study Experience
Test System Number of
1-month Studies
Number of
3-month Studies
Mouse 32 18
Rat 86 76

2) Provide a list of references for similar contract work that generated toxicity study data
and what chemicals or classes of chemicals were tested for these applications, including
whether such contract work was provided for Federal or state regulatory or research
agencies;

Unfortunately, we cannot provide detailed information on chemicals, classes of
chemicals, or customers due to nondisclosure agreements with our clients.
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251 Ballardvale Street, Wilmington, MA 01887 • 781.222.6000 • Fax [phone] • www.criver.com
3) Provide a list of certifications for the specified bioassays;

There is no certification program from either the EPA or the FDA for toxicity testing in
animals. However, we do have extensive experience in multiple different study types (as
noted previously).
Approximately half of the 3-month studies performed were performed for clients
submitting to the EPA, or would have been run in general accordance with appropriate
EPA/OECD guidelines, such as the OECD 408 (Repeated Dose 90-Day Oral Toxicity
Study in Rodents).
In recent past, the EPA was commonly requiring the OPPTS 870.7800 (Immunotoxicity)
be performed for compounds, but more recently these requests are targeted based on the
chemical class, rather than for all compounds. While we have not run any OPPTS
870.7800 guideline studies recently, we have conducted the following immunotox studies
in that timeframe:
 1 mouse AFC assay
 sRBC IgM ELISA for 2 rat studies (2 additional studies scheduled this year)
 rat splenic immunophenotyping assay on 7 studies (3 additional studies scheduled
this year)
 rat peripheral blood immunophenotyping assay on 23 studies (4 additional studies
scheduled this year)
 mouse peripheral blood immunophenotyping assay on 2 studies
4) Source of the testing animals

Rats and mice used for toxicology studies at Charles River Ashland are primarily
received from the Charles River breeding facility in North Carolina.
5) Source of the testing material and how will it be characterized chemically for dosing

The test substance is often supplied by the Sponsor. The Sponsor typically provides
documentation of the identity, strength, purity, composition, and stability for the test
substance, often in the form of a Certificate of Analysis and/or other accompanying
documentation.
For analysis of dose formulations, an appropriate analytical method is developed and
validated for determination of the concentration of test substance in the appropriate
vehicle (or matrix). For each in vivo study, samples of the dose formulations (including
vehicle) are collected for subsequent chemical analysis to determine the
presence/quantity of the test substance.
6) List any affiliation with DuPont, Chemours or any of their associated companies

Charles River is a publicly traded company whose customers include pharmaceutical,
biotechnology, agrochemical companies from around the world. We support basic
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251 Ballardvale Street, Wilmington, MA 01887 • 781.222.6000 • Fax [phone] • www.criver.com
research, discovery, safety and efficacy, clinical support and manufacturing. We are not
affiliates of Chemours, DuPont or or any of their associated companies.
For more information, please visit https://www.criver.com/about-us.

We are appreciative for the opportunity to submit this input and look forward to supporting the
State of North Carolina and Chemours in their future mammalian toxicology efforts. Please don’t
hesitate to let us know if you need additional details.

Sincerely,

Erica L. Lashley, MBA, BS, LAT
Site Director – Safety Assessment Ashland
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