Carcinogenicity Testing

Carcinogenicity studies involve exposing rodents to your product for a maximum of two years. We collect extensive in-life, survival, and histopathology data, and perform full statistical data analysis to evaluate tumor parameters. Our board-certified pathologists use comprehensive historical control data that incorporates the highest standards of husbandry. 

Carcinogenicity studies at Charles River comply with EU (CPMP), ICH, FDA, EPA, JMHW, JMAFF, and OECD regulations. Requirements are similar for all studies, though the testing of agrochemicals and industrial chemicals can combine carcinogenicity studies with a long-term chronic toxicity study.

Routine carcinogenicity species include:

Transgenic Models

Under ICH S1, regulatory authorities (e.g., FDA, EMA CHMP, and PMDA) accept that carcinogenic potential can be evaluated from data collected in a two-year rat bioassay, plus a short-term mouse study using a transgenic model. We’ve evaluated these alternative models as part of The International Life Sciences Institute (ILSI) program. A 26-week study in the transgenic Tg.rasH2 mouse model is commonly selected as a replacement for the standard two-year mouse study.

Historical transgenic alternatives to two-year mouse carcinogenicity studies include:

  • Tg.rasH2 mouse for genotoxic/non-genotoxic compounds
  • p53 +/- mouse for known genotoxic compounds
  • Tg.AC mouse for dermal drugs

These carcinogenicity models were initially accepted by regulatory agencies as the result of a multinational effort by The ILSI/Health and Environmental Sciences Institute’s Alternatives to Carcinogenicity Testing Project in conjunction with the directives of ICH S1B, from 1996 to 2001. However, the TG.AC and p53 +/- models have not been actively used for some time and the lines are currently cryopreserved. Accordingly, the rasH2 model has become the model of choice most often used as a replacement for a traditional two-year mouse carcinogenicity studies.

We’ve conducted more than 60 carcinogenicity studies with the transgenic rasH2 mouse model since 2013, and are happy to offer this alternative to the full two-year carcinogenicity study.


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Looking for a mouse or rat model? Learn more about our transgenic mouse and rat model creation services

 

Frequently Asked Questions (FAQs) about Carcinogenicity Studies

  • What are carcinogenicity studies?

    Carcinogenicity studies are used to evaluate the carcinogenic potential of products where there is prolonged exposure.

  • What are transgenic carcinogenicity study models?

    Transgenic mice are used as models for carcinogenicity studies as they have an activated/overexpressed oncogene and are much more susceptible to carcinogens than normal mice. This results in a more rapid induction of tumorigenesis, saving valuable time and resources. Learn more

  • Can I use CD-1 mice for range-finding studies, such as a six-month transgenic carcinogenicity study?

    While previous data in other mouse strains may inform dose level selection, the actual range-finding studies should be conducted in the wild-type background mouse strain used for the transgenic model. We have observed dramatic strain differences in pharmacokinetics and test article toxicity between CByB6F1 wild-type littermates and common mouse strains such as CD-1 mice.

  • Is there a transgenic model available for dermal programs?

    Not at this time. The Tg.AC model was previously accepted as a transgenic alternative to a two-year mouse carcinogenicity study, specifically for dermal programs. However, this model had a high incidence of false positives and there were concerns by certain regulatory agencies about the stability of the transgene. Consequently, the model has not been used for years and the line is currently cryopreserved.

    While there are publications that indicate that the rasH2 model provides a good response to carcinogens when applied dermally, regulatory agencies (particularly the FDA) do not consider the model validated for dermal administration. Therefore, for dermal programs, a two-year mouse carcinogenicity study is warranted.