Laboratory of Developmental and

Reproductive Toxicology

Developmental Toxicology Studies

Extensive experience and expertise in development of protocols, performance of studies and interpretation of results in rats, mice and rabbits with in-house historical control databases. All studies performed according to Good Laboratory Practice (GLP) and governmental study guidelines for FDA (Segment II), EPA (FIFRA/TSCA), OECD, or ICH (International Conference on Harmonization) Guidelines, and U.S. EPA OPPTS Prenatal Developmental Toxicity Study Testing Guideline (OPPTS 870.3700 Final, August 1998, Public Draft February 1996; U.S. EPA TSCA version 799.9370, August 15, 1997), with Standard Operating Procedures (SOPs) in place and RTI Quality Assurance Monitoring of all critical phases. Client confidentiality strictly maintained. Studies performed on time and within budget. Study designs can include multiple replicates and double staining of fetal skeletons (for ossified and cartilaginous elements) and can be customized. Routes of administration include gavage, dosed feed, dosed water, cutaneous application, injection (iv, sc), and subcutaneous implants (inhalation in collaboration with CIIT).

Range-Finding Developmental Toxicity Studies

Extensive experience and expertise in design, conduct and interpretation of range-finding studies to establish appropriate doses for definitive studies. Performed under appropriate GLPs.

Reproductive Toxicity Studies

Extensive experience and expertise in development of protocols, performance of studies and interpretation of results in rats with in-house historical control data base. All studies performed according to GLPs and governmental study guidelines for FDA (Segment I and III), EPA (FIFRA/TSCA), OECD, or ICH one- and multi-generation studies, with gavage, dosed water, or dosed feed routes of administration (inhalation in collaboration with CIIT), and U.S. EPA OPPTS Reproduction and Fertility Effects Testing Guideline (OPPTS 870.3800 Final, August 1998, Public Draft February 1996; U.S. EPA TSCA version 799.9380, August 15, 1997). EDSTAC recommended Tier 1 screening assays and Tier 2 tests in mammals (Dr. Tyl was an invited member of EDSTAC, 1996-1998). NTP Reproductive Assessment by Continuous Breeding (RACB) studies in rats or mice with routes and oversight as above.

In-house Capabilities Support capabilities include hematology, clinical chemistry, histopathology, blood and organ enzyme assays, chemical characterization of test matrices, analyses of dosing formulations for homogeneity, stability and test chemical content, analysis of parent compound and/or metabolite(s) in various biological materials (e.g., blood, milk, urine, feces, organs, embryos, fetal tissues, amniotic fluid, etc.), developmental and adult neurotoxicology, toxicokinetics, detailed male and/or female reproductive toxicity assessments, including endocrine, andrologic, behavioral and specialized histologic assays.

Range-Finding Reproductive Toxicity Studies

An abbreviated flexible protocol is available to assess effects of test materials on mating, gestation, parturition, lactation, and on self-feeding periweanling animals to establish appropriate doses for definitive studies. Performed under appropriate GLPs.

Other Study Paradigms

Chernoff-Kavlock Assay in rats or mice, as originally validated or modified to provide additional dose levels, and ancillary evaluations of dams and offspring, including evaluation of ossification in perinatal offspring. OECD Guidelines protocols

OECD Guidelines protocols "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (Repro Tox)" (OECD 422); "Reproduction/Developmental Toxicity Screening Test " (OECD 421); "90-day study " (OECD 408); "One-generation study " (OECD 415); "Two-generation study " (OECD 416); "Dominant lethal study " (OECD 478), etc.

International Harmonization Guidelines protocol "Screening Information Data Set" (SIDS) for Reproductive and Developmental Toxicity. International Conference on Harmonization (ICH) Guidelines on Detection of Toxicity to Reproduction for Medicinal Products (4.1.1, 4.1.2, 4.1.3, 4.2 and 4.3). Dominant Lethal Assay in rats or mice after acute or long-term exposure. Alternate study protocols are available or can be designed at the request of the client.