Reproductive Toxicity

The study of reproductive toxicity is an important step in the clinical research and marketing authorization of pharmaceuticals. Aimed at revealing the impact of drugs on mammalian reproductive functions, and embryonic and fetal development, these studies constitute a vital aspect of non-clinical safety assessment of drugs. The main purpose is to reflect the impact of the test substance on the reproductive function and development process of mammals through animal testing, and to predict its possible adverse effects on reproductive cells, fertility, pregnancy, delivery, lactation and other parental reproductive functions, as well as the adverse effects on the embryo-fetal development of the offspring and post-natal development.

Based on the research and development strategy and timeline, combined with the structural characteristics, physical and chemical properties, pharmacological and toxicological information, indications, applicable populations, clinical medication plans, etc., Medicilon will provide clients with flexible solutions design and execution for stage I, II and III reproductive studies to help to conduct the clinical studies smoothly.

Service Content:

For drugs intended for human use, reproductive toxicity testing should be conducted based on factors such as the intended indications and pharmacological characteristics of the test substance. Medicilon’s reproductive toxicity test includes:
(1) Segment I reproductive toxicity test:
Fertility and early embryonic development toxicity test, also known as general reproductive toxicity test. Administration period starts from pre-mating to implantation, evaluating the impact of the drug on fertility and early embryo development.
Fertility and early embryonic development toxicity test, also known as general reproductive toxicity test. Administration period starts from pre-mating to implantation, evaluating the impact of the drug on fertility and early embryo development.
The content of toxicity assessment: general paternal and maternal toxicity, fertility, early embryonic development toxicity (death)
(2) Segment II reproductive toxicity test:
Embryo-fetal development toxicity test (segment II), also known as teratogenic sensitive period toxicity test. Administration of test article during organogenesis, the study aims to reveal potential embryo-fetal toxicity and teratogenicity of the drug.
Evaluation parameters include: toxicity to pregnant animals, embryonic fetal death, changes in fetal appearance, changes in internal organs and soft tissues, and changes in bone quantity and morphology.
Toxicity assessment content: general maternal toxicity, embryo-fetal developmental toxicity (death, malformation, developmental abnormalities)
(3) Segment III reproductive toxicity test:
Pre-natal and post-natal reproductive toxicity test, in which drugs are administered during the perinatal and lactation periods to observe the effects of the drug on the growth and development of the fetus after birth.
This test is to assess toxicity in pregnant animals, pre- and post-natal survival of offspring, changes in the growth and development of offspring, and functional defects, including sensory function, spontaneous activity, learning and memory, sexual maturity, and reproductive capacity at maturity.
Toxicity assessment: general maternal toxicity, delivery, lactation, offspring developmental toxicity (death, malformation, developmental abnormalities, functional toxicity)

Dose description indicators for reproductive/developmental toxicity

Typically, a NOAEL or LOAEL can be obtained from reproductive/developmental toxicity studies. NOAEL/LOAEL can further be used for quantitative risk assessment.
No Observed Adverse Effect Level (NOAEL): The highest dose or concentration of a test article that does not cause a detectable harmful change in body shape, function, growth, development, or lifespan under specified exposure conditions.
Lowest Observed Adverse Effect Level (LOAEL): The lowest dose or concentration of a test article that will cause an adverse change in body shape, function, growth, development, or lifespan under specified exposure conditions.
The unit of NOAEL or LOAEL: mg/kg/day.

Guidance for reproductive toxicity

Reproductive/developmental toxicity screening test (OECD TG 421) Prenatal developmental toxicity testing (OECD TG 414) Two-generation reproductive toxicity study (OECD TG 416) Extended Generation Reproductive Toxicity Study (EOGRTS; OECD TG 443)ICH S5(R3)ICH M3(R2)

Animal species

SD rats, New Zealand rabbits and cynomolgus monkeys

Research content

Type of test	Animal species	Type of drug	Route of drug Administration	Research content
Reproductive toxicity	Rat	Small molecules, biological products, natural products, vaccines, traditional Chinese medicine	Oral administration, intravenous injection, intramuscular injection, intradermal injection, subcutaneous injection, continuous infusion,	Segment I, II, III reproductive toxicity tests,
	Rabbit			Stage II Reproductive Toxicity Test
	Cynomolgus monkeys			Segment II, ePPND

Advantage

Medicilon’s reproductive toxicity research service platform is led by senior reproductive toxicity experts, comprising a professional technical team.
The animal laboratory was jointly established by Medicilon and the American MPI Research Company (American Toxicology Research Company) in 2007 which passed the International Laboratory Animal Assessment and Recognition (AAALAC) and reached the GLP double standard of FDA and NMPA/CFDA;
Experimental instruments such as HamiltonThorne-TOX IVOS fully automatic sperm analyzer, imaging stereoscope, Leica microscope, etc. all meet high-precision experimental requirements; the complete equipment with rich resources gives Medicilon's reproductive toxicity research service platform a great advantage in the industry, and can ensure the quality and efficiency of services.

Relevant articles

Reproductive Toxicity Genotoxicity Study General Toxicology