02102nas a2200181   4500000000100000000000100001008004100002260001500043100001600058700002300074700001600097245012700113856004600240300001200286490000700298520160100305022001401906       2025                            d  c2025-05-011 aKaty Taylor1 aLaura Rego Alvarez1 aEmma Grange00aThe Prevalence of Reported Gavage Incidents in Repeated Dose Toxicity Studies Involving Rats Conducted Between 2004–2023  uhttps://doi.org/10.1177/02611929251334721  a154-1670 v533 aIn animal-based toxicology studies, oral gavage is the predominant technique for administering compounds directly into the stomach. Recognised as a stressful procedure for animals, gavage is associated with accidents and ‘gavage-related reflux’ (GRR), which may lead to respiratory distress and/or death. This paper estimates the prevalence of incidents (deaths and/or non-fatal clinical signs) attributed to the gavage procedure in a representative sample of repeated dose toxicity test reports from the last 20 years, sourced from the ECHA CHEM database of REACH-registered chemicals. In 21% of the 300 reviewed studies, at least one death or clinical sign in rats was attributed to the gavage procedure in the study report. An additional 16% of these studies reported clinical signs associated with GRR in the animals, with no other adverse effects, but without attribution to the gavage procedure. Among those studies with incidents attributed to the gavage procedure, incidents were three times more common in 90-day studies than they were in 28-day studies. Incidents were also more likely to have occurred with the test substance rather than with the control, with highly viscous substances, and in more recently conducted studies. There was no association between the number of studies with a gavage-attributed incident and the strain, size or age of the rats, the dose volume or the testing of irritant substances. The current study suggests that incidents attributed to gavage are more prevalent than previously thought, and that a review of the gavage procedure is urgently needed.  a0261-1929