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Case Study

October 11, 2016

Repeated dose toxicity study

6-week repeated dose toxicity study by intranodal administration of a cat dander allergen in the beagle dog, followed by an 8-week recovery period

The aim of this study was to obtain information about toxicity, local tolerance at the injection sites as well as tolerability and immunogenicity of the test item after intranodal injections.
The intranodal route of administration corresponded to the intended therapeutic use in humans.

The test item was injected intranodally into the popliteal lymph node at a volume of 50 μl/lymph node in conscious dogs.

An intranodal injection in dogs can be performed into the popliteal lymph nodes fixed with palpation. With a suitable size of needle and an administration volume, the injection is well controlled. However, the histopathological confirmation of the successful treatments is desirable.

Monitoring of standard parameters of a repeated dose toxicity study (including lymphoid organs) lead to identification of toxicological targets and assessement of NOAEL and MTD. Additionally, histopathologic alterations of the popliteal lymph nodes (and the surrounding tissues) were investigated and the serum levels of cat allergen extract-specific IgG (ADA) were determined.

Intranodal injection in most cases induced inflammation (lymphadenitis) of different grades in popliteal lymph nodes without affecting their physiological structure. In this study, histiocytosis, epitheloid cell formation, and a sporadically recorded slight necrosis have been considered secondary reactions to the inflammation. The histiocytes (phagocytes) often were loaded with foamy material that most probably consisted of persisting aluminum hydroxide. All these findings demonstrated also the successful intranodal injections.

Intranodal injections of the adjuvanted test item lead to high drug-specific IgG titers in each test item-treated groups.
In this study, no treatment-related findings were observed in any other investigated parameters and no macroscopical or microscopical alterations were detected in any tissues (including lymphoid organs).

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