Den Bosch, The Netherlands: Safety Assessment

Satisfy the safety assessment requirements for the global registration of your chemical, biocide, agrochemical, or pharmaceutical at our site in Den Bosch, the Netherlands. Here, you’ll find fully integrated toxicology and laboratory support in addition to specialized expertise in environmental toxicology, bioanalysis, and REACH to meet all your testing needs.

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Charles River offers a full-service portfolio in environmental toxicology, toxicology and bioanalysis services in Den Bosch, The Netherlands.

Safety Assessment Services

Featuring 58 animal rooms and 12,000+ square metres of laboratory space, our full-service safety assessment facility in Den Bosch is staffed by more than 400 scientists. Together with diverse support staff, the team delivers comprehensive range of services for the development of human and veterinary pharmaceuticals, as well as agrochemicals and industrial chemicals.

The facility has been GLP compliant since 22 Sep 1987 (1e GLP endorsement), AAALAC-accredited since 2012.

Acute to Chronic Toxicology

Access a comprehensive range of standard and specialty toxicity studies, from acute inhalation studies to 104-week carcinogenicity, in all recognized laboratory animal species. Administration routes include oral, subcutaneous, intramuscular, dermal and ocular.

 

Developmental and Reproductive Toxicology (DART)

From program planning and individual study design to execution per internationally recognized guidelines like ICH and OECD, our skilled team can help you satisfy complex developmental and reproductive toxicology (DART) requirements. Our multigenerational study portfolio includes the Extended One-Generation Reproductive Toxicity Study, required to satisfy OECD Guideline 443.

Available study designs include:

    •     OECD 414 Prenatal Developmental Toxicity Study
    •     OECD 416 Two-Generation Reproduction Toxicity
    •     OECD 421 (Screening) or OCED 422 (Combined) Reproductive Toxicology Study
    •     OECD 443 Extended One Generation Reproductive Toxicity Study
    •     OECD 426 Developmental Neurotoxicity Study
    •     Developmental Immunotoxicology & Immunotoxicity (OPPTS 870-7800)
    •     Fish Embryo Acute Toxicity Test (OECD 236)

 

Drug Metabolism & Pharmacokinetics

The scientists at our Den Bosch facility can help you design and execute a definitive DMPK/ADME program to support your drug discovery and development needs:

    •     In vitro metabolism
    •     In vivo ADME
    •     Pharmacokinetics
    •     Mass balance
    •     QWBA (tissue distribution)
    •     Biotransformation
    •     Metabolite profiling and transformation

 

In Vitro Toxicology

Access our team’s expertise in dermal absorption, sensitization, and phototoxicity, as well as both dermal and ocular corrosion and irritation with a comprehensive range of available studies. As required, our scientists also use bespoke and innovative technologies to design and evaluate new in vitro assays.

Sensitization

•    Kinetic DPRA (OECD 442C)
•    KeratinoSens (OECD 442D)
•    uSENS (OECD 442E)

Absorption

•    Selection of lead formulation
•    In vitro dermal absorption (OECD 428)

Phototoxicity

•    3T3 Neutral Red Uptake NTU) (OECD 432)
•    Photo EpiDerm®

Corrosion

•    MatTek Epiderm (OECD 431)
•    Corrositex® (OECD 435)
•    Bovine Cornea and Opacity Permeability (OECD 437)

Irritation

•    SkinEthic EpiSkin® (OECD 439)
•    MatTek Epiderm (OECD 439)
•    MatTek EpiOcular® (OECD 492)
•    HET (Hen’s Egg Test)-CAM

 

Genetic Toxicology

Meet the unique requirements of your chemicals and drugs with help from our genetic toxicologists. In addition to the regulatory core battery studies, the site also offers custom testing strategies, discovery screening, and specialty assays such as unscheduled DNA synthesis and in silico support through Quantitative Structure Analysis (QSAR) - DEREK, SARAH and Leadscope.

 

Endocrine disruptors

Charles River offers custom endocrine disruptor testing services and consultancy, combining excellent project communication and support from our dedicated team of experts. With rapid turnaround times, we are also able to shorten timelines with our testing program.

A comprehensive portfolio of in vitro and in vivo study designs is offered, including amphibian metamorphosis and fish assays.

 

Environmental Risk Assessment (ERA)

Combining our expertise on technical aspects of testing and regulatory context enables us to build the most efficient and suitable dataset for your product. Our team of experts includes study directors with many years of experience in physico-chemical properties, analytical methods, environmental fate, and ecotoxicology testing, as well as regulatory consultants with a high level of scientific expertise and know-how on regulatory aspects. Leveraging our vast experience in conducting risk assessments for a variety of legal frameworks, we can find the best solution for your drug. By following both emerging guidelines and changes in existing guidelines, we know what will be required and how to meet regulator’s expectations.

Bioanalytical Chemistry

From rapid PK screening to support drug candidate selection to the analysis of samples from nonclinical studies, the expert analysts leverage state-of-the-art technology, which includes but not limited to LC/GC and ICP-MS, to ensure a streamlined bioanalytical service that helps you make confident research decisions.

Trust our team to develop or transfer, optimize, validate, and apply quantitative bioanalytical methods to measure drug and metabolite concentrations for samples of most any biological fluid, including both standard whole blood, plasma, serum, cerebrospinal fluid (CSF), urine, and more unconventional matrices such as liver, brain, kidney, lung, muscle and skin.

 

Analytical Chemistry

Experienced analytical scientists at the Den Bosch site provide support for toxicology, metabolite ID, and environmental studies as well as substance or impurity identification, and extractables and leachables from packaging.

 

Formulation Analysis

The laboratory performs formulation/dietary analytical support for more than 200 studies annually, as well as dose confirmation analysis for more than 300 ecotoxicology studies per year.

 

Physicochemical Analysis

A dedicated team of chemists can help you understand the properties of your agrochemicals and pesticides, including insecticides, herbicides, fungicides and biocides. We have also worked with a wide variety of industrial chemicals, including dyes, flavor and fragrance substances, monomers, fluorinated chemicals, and inorganics.

 

Anatomic and Clinical Pathology

A comprehensive range of specialty, pathology-based services are available at the Den Bosch site:

    •     Necropsy
    •     Histology
    •     Histopathology
    •     Peer review
    •     Hematology
    •     Biochemistry
    •     Urinalysis
    •     Immunohistochemistry

Environmental fate & biodegredation

Charles River, Den Bosch can support the environmental fate (eFate) testing needs of your pharmaceutical, industrial and agrochemicals development program in our modern, open-plan, flexible laboratories using soils, sediments and natural waters sourced from sites worldwide. The viability (biomass) of each test system is verified (if applicable) prior to study initiation.

Study designs include:

    •     Aerobic and anaerobic degradation in soils and sediment waters (OECD 307 & OECD 308)
    •     Aerobic mineralization in surface waters (OECD 309)
    •     Ready and inherent biodegradation (OECD 301 A-F & OECD 302B)
    •     Soil or sludge adsorption, desorption and mobility investigations (OECD 106)
    •     Hydrolytic stability and accelerated hydrolysis studies (OECD 111)
    •     Photolytic degradation – moist and dry soil surfaces, aqueous systems (OECD 316)
    •     Studies may be conducted using either radiolabeled or non-radiolabeled test item

 

Aquatic Ecotoxicology

Assess the toxicity, in vitro and in vivo, of your test article to a range of species including fish and frogs with our portfolio of Aquatic Ecotoxicology studies. All aquatic ecotoxicology testing is fully supported by our integrated analytical services for the method validation and routine analysis.

    •     Activated sludge respiration inhibition (OECD 209)
    •     Algal growth inhibition (freshwater and marine) (OECD 201)
    •     Acute and prolonged toxicity to Daphnia magna (OECD 202, OECD 211)
    •     Acute (96-hour) and prolonged toxicity to cold- and warm-water fish (e.g., rainbow trout, bluegill sunfish, carp, fathead minnow, and zebrafish) (OECD 203)
    •     Fish embryo toxicity test (FET test) (OECD 236)
    •     Fish, toxicity test on egg and sac-fry stage (OECD 212)
    •     Fish early life stage (OECD 210)
    •     Radiolabeled (or cold) bioaccumulation and/or metabolism in fish (OECD 305)
    •     Lemna sp. growth inhibition (OECD 221)
    •     Acute and prolonged sediment water toxicity test to Chironomus riparius (OECD 235, OECD 218, OECD 219)
    •     Sediment-water toxicity test with Lumbriculus (OECD 225)

Our in-house regulatory team of 25+ experts has completed hundreds of registration dossiers over several decades. Take advantage of their diverse scientific background, experience with European regulatory bodies, and knowledge of global industrial chemical, biocide, agrochemical and pharmaceutical requirements.

    •     Full registration package or parts thereof, e.g., data gap analysis, testing/regulatory strategy
    •     Substance and product registrations/authorizations
    •     IUCLID and OECD summaries, CADDY
    •     QSARs (DEREK, SARAH, Leadscope), ICH M7, Read across, grouping
    •     Hazard, (higher tier) exposure and risk assessments for human and/or environment
    •     Classification and labeling, CLH dossiers
    •     Project Coordination, Consortia support
    •     Contacts with authorities, e.g., ECHA, EC, and working for national authorities
    •     Expert statements incl. literature search, justifications on decisions/comments from authorities
    •     Consultancy: Regulatory and scientific knowledge and experience
    •     Pre- and post-submission support
    •     Study monitoring