Acute Histopathologic Findings Related to Needle Puncture Trauma during Subcutaneous Injection in the Sprague-Dawley Rat Model

Abstract

It is important to detect injection site reactions during the nonclinical phases of drug development. However, differentiating between normal changes following needle trauma and changes due to the toxicity of injected drugs can be challenging. Therefore, we used the Sprague-Dawley rat model to evaluate the pathological findings expected following a single subcutaneous injection of normal saline. Rats were subcutaneously administered with normal saline, and the injection sites were examined microscopically. Inflammation was evident in most of the injection sites, mostly in minimal severity. Parakeratosis/epithelial crust was also seen in several sites, and necrosis was observed in a minority of the cases. These findings indicate that needle puncture trauma can present with some degree of inflammation and necrosis. Although limited to a specific time point and strain, this study shows that inflammation following subcutaneous injection can be attributed in part to the needle trauma and not necessarily to the drug itself.

rVSV-ΔG-SARS-CoV-2-S vaccine: repeated intramuscular (IM) toxicity, local tolerance, immunogenicity and biodistribution study in NZW rabbits

“…The injection site lesions of minimal focal epidermal crust formation and epidermal hyperplasia, sporadically seen in control and treated animals, as well as multifocal mixed mononuclear cell infiltration seen in the underlying skeletal muscle of the control group, are considered to be related to the needle puncture trauma, as previously reported in similar circumstances (Ramot et al 2019 ).…”

Nasal Inflammation and Ulceration Secondary to Repeated Use of an Intranasal Delivery Device in Rabbits

“…9 Such anatomical differences can also lead to trauma-induced pathological changes related to the handling of the animal, and it is important that the toxicologic pathologist will not wrongly attribute such changes to the test drug or combination product. [10][11][12] Here, we report on nasal inflammation and ulceration in rabbits, secondary to the mechanical damage induced by the repeated insertion and removal of the intranasal device, which were not related to the tested drug.…”

“…The nature of the changes in the nose, being focal, unilateral, hemorrhagic, ulcerative, and localized to the mucosa and underlying submucosa, suggests a mechanical puncture/ scratch trauma, as was previously shown by our group in the case of subcutaneous injection of saline. 10 Knowledge of these changes that are induced by the traumatic application of the nasal device is important for the correct interpretation of future safety studies. This is especially true for studies performed in rabbits, where the nasal anatomy is more complex making rabbits more susceptible to nasolacrimal obstruction and infection, which may result in ocular infection.…”

“…9 Such anatomical differences can also lead to trauma-induced pathological changes related to the handling of the animal, and it is important that the toxicologic pathologist will not wrongly attribute such changes to the test drug or combination product. 10 –12…”

Local Tolerability and Performance Evaluation in Domestic Pigs of a Fractional Radiofrequency Device for Dermatologic Treatment

“…23 In accordance with the increasing number of medical devices being developed, information on preclinical animal trials with such devices is also growing. [24][25][26][27][28] Specifically for fractional RF devices, it is important to evaluate the consistency and lack of fractional RF effects in the tissue adjacent to the application site, and the lack of any inflammatory reaction at the surrounding tissue. Furthermore, it is essential to observe that normal wound healing process takes place in the application site, with formation of normal skin at this site.…”