Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
other information
Study period:
data not available
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-standard study

Data source

Reference
Reference Type:
publication
Title:
Effects of chronic salicylate on GABAergic activity in rat inferior colliculus
Author:
Bauer CA Brozoski TJ, Holder TM, Caspary DM
Year:
2000
Bibliographic source:
Hearing Research, 147, 175-182.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
"Salicylate"

Test animals

Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: between 7 and 12 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: individually in cage
- Diet : no data
- Water : no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: no data


Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 months (animals behaviorally tested for evidence of tinnitus)
4 weeks (animals not behaviorally tested for evidence of tinnitus)
Frequency of treatment:
daily
Post exposure period:
no
Doses / concentrations
Remarks:
Doses / Concentrations:
8 mg/ml
Basis:
nominal in water
No. of animals per sex per dose:
10 males per dose (behaviorally tested for evidence of tinnitus)
5 males per dose (no behaviorally tested for evidence of tinnitus)
Control animals:
yes, concurrent no treatment

Examinations

Examinations:
The following parameters were observed: daily fluid consumption, weekly weights, serum salicylate levels, auditory brainstem response thresholds,
GAD (Glutamic Acid Decarboxylase) levels in the inferior colliculus and GABA receptor binding characteristics.
Positive control:
no

Results and discussion

Details on results:
The serum salicylate level ranged from 9.89 to 38.2 mg/dL. No detectable levels of salicylate were present in control sera. The total mean daily dose of salicylic acid ingested by the subjects that were not behoviorally tested was 563.2-661 mg/kg/d. The weight of the subject was stable throughout the duration of the study. Auditory brainstem response testing revealed a 3.8 dB difference in the
mean threshold. Western blotting revealed a significant 63% (p < 0.008) elevation of GAD levels in the inferior colliculus (IC) ofsalicylate-treated
subjects. GAD expression and GABAa receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.

Applicant's summary and conclusion