Freeze-dried equine-derived redback spider antivenom: a local irritation study by intramuscular injection in rabbits and a repeated-dose toxicity study in rats

The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Toxicologic Pathology 2018, Vol.31(2), pp.105-112
Main Authors: Yamamoto, Akihiko, Harano, Satomi, Shinya, Noriko, Nagano, Ayataka, Miyatsu, Yoshinobu, Sawabe, Kyouko, Matsumura, Takayuki, Ato, Manabu, Takahashi, Motohide, Taki, Hisashi, Hifumi, Toru
Format: Article
Language:English
Subjects:
Animal bites
Antivenom
Diphtheria
equine polyclonal antibody
Freeze drying
freeze-dried redback spider antivenom
Immunization
Infectious diseases
Insect bites
Intravenous administration
Irritation
local irritation study
Medical research
Original
R&D
Rabbits
Rats
repeated-dose toxicity study
Research & development
Rodents
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom’s irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverse-effect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development.
ISSN:0914-9198
1881-915X
1347-7404
DOI:10.1293/tox.2017-0053