NTP has gathered a significant database of results collected on chronic toxicity and carcinogenicity studies, as well as developmental and reproductive studies. To evaluate study results and follow changes in the biology of our test species, we maintain a historical summary of the observations made on the untreated or control groups from individual studies. These data are divided into categories depending on the study type. Due to a variety of factors that can influence response, historical control data may be identified by:
- Route of administration
- Study type
History of Rat Models Used by NTP
Commentary: Update on Animal Models for NTP Studies contains a thorough discussion on rat strain selection considerations. The following history summarizes part of the discussion.
For more than 30 years, NTP used the inbred F344/N rat for toxicity and carcinogenicity studies. Over time, this substrain developed decreased fecundity, sporadic seizures, and idiopathic chylothorax. The F344/N possessed other health issues inherent to the strain including high rates of mononuclear cell leukemia and testicular neoplasia.
In 2005, NTP held the NTP Workshop: Animal Models for the NTP Rodent Cancer Bioassay: Stocks and Strains—Should we Switch? Workshop participants recommended three options to NTP:
- Establish another colony of the F344 rat from another source
- Use a F1 hybrid
- Use an outbred stock of rat such as the Wistar Han or the Sprague Dawley
NTP temporarily switched to the F344/NTac rat and then selected the Wistar Han rat [Crl:WI (Han)]. However, in several studies with perinatal exposure, the average litter sizes were smaller than expected, the litters had a high variability in sex distribution, and pregnancy rates in time mated Wistar Han rats were not acceptable.
Consequently, NTP adopted the Sprague Dawley (Hsd:Sprague Dawley SD) rat as the default NTP rat strain. NTP's decision came after much deliberation including consideration of historical data from eight previous NTP cancer studies using the female Sprague Dawley rat, and very favorable data on litter size, sex ratio, and body weight.
Chronic Toxicity & Carcinogenicity Studies
Chronic toxicity and carcinogenicity studies are labeled in the NTP Historical Controls database under study type as "Chronic." Specific information, including pathology tables, body weights, survival curves, and chemicals by sex/species may be viewed from the database. The data for control animals are compiled from the most recent five-year window.
- Within the pathology tables, tumor incidence is defined as the number of animals exhibiting a tumor type divided by the number of animals examined and is expressed as both raw counts and percent.
- The pathology tables present the mean and standard deviation of tumor incidence among studies, along with the number of studies summarized.
- The growth and survival curves present the mean for each route, species, and sex group of control animals along with the 5th and 95th percentile.
Note: The historical controls data for genetically modified models are displayed separately.
Developmental & Reproductive Toxicity Studies
Users can search data related to developmental and reproductive toxicity (DART) studies within the NTP Historical Controls database. The database includes information on fetal defects from stand-alone prenatal development (i.e., teratology) studies or modified one-generation studies (MOG). Files presenting data on fetal findings can be found in the database under "All Routes and Vehicles."
In the fetal findings file, under the "Summary" tab, fetal findings (Column C) are further delineated by exam type (Column A), followed by body area (Column B). Data are presented as the number of fetuses or litters with a finding and the percentage calculations are in parentheses.
- Rows in bold reflect the total number of fetuses or litters per finding. Columns labeled "TOTAL_FETUS" and "TOTAL_LITTER" indicate the total number of findings per fetus and per litter in all studies presented here.
- Columns labeled "MIN_FETUS," "MIN_LITTER," "MAX_FETUS," and "MAX_LITTER" indicate the minimum and maximum number of fetuses or litters with that finding.
NTP Historical Controls Database
How to search with filtering and sorting
Search for particular tables by filtering or sorting the table. As you begin to type your search entry, the page will filter the table results by text. For example, type "F344" to see Fischer F344/N Rats rows.
To sort the table by a specific column, click the up/down filter arrow in the table header for that column. When clicked, the column headers will sort the table by ascending or descending order. If only one arrow is displayed, that column is sorted in the direction of the arrow. To sort more than one column, click the first column header, and then hold the shift key and click on additional column headers.
Download Earlier Historical Controls
||Species: Strain||Diet||Years Study Started||All Routes/
||Growth Curves By Route/
||Survival By Route/
||Rats: Harlan Sprague-Dawley||NTP-2000||1998-2004||Pathology Tables for All Routes/
Note: These reports cover more than five years so that all
the Toxic Equivalency Factor studies would be included.