Lymphoid depletion (spleen, thymus, Peyer's patches, BALT) in all three species, at toxic doses
“Signs of immunotoxicity were seen in most of the repeat-dose toxicity studies and in all three species, such as lymphoid depletion in the spleen, thymus, Peyer’s patches and bronchial-associated lymphoid tissue in the lungs, and alterations in lymphoid organ weights.”
Rat: highest in Harderian gland, liver, kidney, adrenal, lacrimal gland and spinal cord
“In a study of radiolabeled PA-824 in rats, the highest tissue concentrations were measured in the Harderian gland, liver, renal medulla, adrenal gland, kidney, renal cortex, exorbital lacrimal gland, and spinal cord.”
✓ VerifiedFDA multi-discipline review, p. 39Source ↗
Modality-specific risk
Male reproductive (testicular) toxicity in rodents without safety margin
“Pretomanid shows clear signs of toxicological effects on male rodent reproductive organs without any safety margin.”