National Toxicology Program Position Statement on Informed (“Nonblinded”) Analysis in Toxicologic Pathology Evaluation

Abstract

The National Toxicology Program (NTP) uses histopathological evaluation of animal tissues as a key element in its toxicity and carcinogenicity studies. The initial histopathological evaluations are subjected to a rigorous peer review process involving several steps. The NTP peer review process is conducted by multiple, highly trained, and experienced toxicological pathologists employing standardized terminology. In addition, ancillary data, such as body and organ weights and clinical pathology findings, are used to corroborate the diagnoses. The NTP does employ masked analysis to confirm subtle lesions or severity scores, as needed, and during its Pathology Working Groups. The use of masked analysis can have a negative effect on histopathological evaluation because it is important for the pathologist to compare treated groups to the concurrent controls, which would not be possible in a blinded evaluation. Therefore, the NTP supports an informed approach to histopathological evaluation in its toxicity and carcinogenicity studies.

Evaluation of Maternal, Embryo, and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid (PFOA) or Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX)

“…Diplomate American College of Veterinary Pathologists (DACVP). Pathology reviews were conducted as an informed approach analysis [e.g., nonblinded analysis; see Sills et al (2019)]. Select tissue slides were scanned using the AT2 Scanner (Aperio).…”

MRI Study of Jellyfish Collagen, Hyaluronic Acid, and Cadaveric Dermis for Injection Laryngoplasty

“…Finally, specimens were mounted with xylene media. Slides were analyzed in a nonblinded manner, consistent with the recommendations of the National Toxicology Position Statement on Informed ("Nonblinded") Analysis 14…”

High-fat Western diet consumption exacerbates silica-induced pulmonary inflammation and fibrosis

“…The left lung was paraffin-embedded and 5 µm sections were prepared for hematoxylin and eosin (H&E), Masson’s trichrome, and picrosirius red staining in order to examine sections for indicators of pulmonary injury, inflammation, and fibrosis by a board-certified veterinary pathologist (R.E.P.). An informed unblinded, semi-quantitative histopathologic assessment was used, as recommended by the Society of Pathology [27] and the National Toxicology Program [28] , to ascertain the distribution and severity of histopathological changes in the lungs at 0, 4 and 8 wk post-exposure in the four animal cohorts.…”