The Guinea Pig: An Effective Solution in Reproductive Toxicology Studies
February 14. 2012 - According to Rocca and Wehner1, the guinea pig may be a viable option for evaluating drugs that are pharmacologically inactive in traditional DART animal models. As a more cost-effective solution to studies in large animals, Charles River has experience using this model in reproductive assessments with a modified ICH 4.1.1 study design. Contact us to learn more.
Developmental and Reproductive Toxicology Studies: Rats, Mice, and Rabbits
Regulatory guidelines for developmental and reproductive toxicology studies call for "relevant" animal models, as determined by kinetic, pharmacological and toxicological data2,3. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. Using such models offers well-established experimental designs, short gestation periods, large litter sizes, good fertility and well-established historical control data. Below is an example of a 4.1.1 Study (Fertility and Early Embryonic Development).
ICH 4.1.1 (Fertility and Early Embryonic Development)
•Life cycle: Premating to conception (Stage A) and conception to implantation (Stage B)
•Species:
•Preferably rat (mouse, good alternate)
•Males and females may be combined in a single fertility
study or separate studies
•Typical treatment period:
•Males: 4 weeks before mating until euthanasia
•Females: 2 weeks before mating until implantation
•Main components:
•Estrous cycling
•Mating and fertility
•Ovarian and uterine contents
•Reproductive organ weights
•Sperm count, motility and concentration
The Guinea Pig in Reproductive Toxicology Studies: An Effective Alternative
Evaluating drugs that are pharmacologically inactive in traditional animal models may call for an alternate species that more closely mimics the metabolic profile of the drug in humans. As described by Rocca and Wehner1, the guinea pig may be a viable option for evaluating test articles that are pharmacologically inactive in the traditional DART animal models. Reproductive toxicology studies in guinea pigs present a cost-effective alternative to studies in large animals.
In addition, guinea pigs can evaluate immunology, infectious disease and spontaneous diabetes mellitus. Guinea pigs also have a longer gestation period compared to other rodent models (~65 to 70 days), which allows one to evaluate the effects of test agents such as abortifacients.
Charles River’s Reproductive and Developmental Toxicologists have experience with guinea pigs in reproductive assessments–with a modified ICH 4.1.1 study design. One modification to the standard fertility study design is the use of timed-mated females, which facilitates synchronization of mating and gestation, delivery and postpartum estrus/mating. In addition, reproductive assessments in treated males and treated females are performed in separate studies. Standard end points are evaluated in each study design, including viability, clinical observations, body weights, mating and terminal procedures (i.e., ovarian and uterine examinations, organ weights, tissue retention and/or sperm evaluations).
Contact Us
Subject matter experts are available to answer any questions you may have regarding the use of guinea pigs in reproductive toxicology studies. Click here to submit your specific question and our scientists will get back to you shortly.
Charles River is a world leader in reproductive and developmental toxicology testing, and is uniquely qualified to address the challenges of biologics testing. Our highly experienced scientists provide the scientific expertise to ensure sound and effective strategies when developing and implementing rationally designed protocols that fulfill all testing requirements.
References
1. Rocca, M.S. and Wehner, N.G. (2009). The guinea pig as an animal model for developmental and reproductive toxicology studies. Birth Defects Research Part B 86 (2): 92-97.
2. Guideline for Industry: detection of toxicity to reproduction for medicinal products & toxicity to male fertility, (ICH) S5(R2), last update November, 2005. Rockville (MD): U.S. Dept of Health and Human Services Food and Drug Administration.
3. ICH Harmonised Tripartite Guideline S6 (R1). Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals; June 2011.
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