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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Repeated dose toxicity study of the test chemical
Author:
Pryor GT et al
Year:
1983
Bibliographic source:
Neurobehav Toxicol Teratol
Reference Type:
review article or handbook
Title:
Review article of the test chemical
Author:
Cosmetic Ingredient Review Expert Panel
Year:
2003
Bibliographic source:
Int J Toxicol

Materials and methods

Principles of method if other than guideline:
The neurotoxic potential of the test chemical given by oral gavage at 0 (vehicle control), 138, 218, 346 and 550 mg/kg for 5 days per week, for 15 weeks in total, was evaluated in male rats using a battery of neurobehavioral tests.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Sodium salicylate
- Molecular formula: C7H6O3.Na
- Molecular weight: 160.1035 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): No data
- SMILES: C1=CC=C(C(=C1)C(=O)[O-])O.[Na+]

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
15 weeks
Frequency of treatment:
5 times per week
Doses / concentrations
Remarks:
0, 138, 218, 346 and 550 mg/kg bw/day
No. of animals per sex per dose:
9 to 10 male rats per dose level
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
Prior to dosing, at 3-week intervals, and at 3 and 6 weeks after cessation of dosing, the rats were subjected to a battery of neurobehavioral tests including undifferentiated motor activity, forelimb and hindlimb grip strengths, rotation orientation, thermal sensitivity, startle responsiveness to acoustic and air-puff stimuli, and performance of a multisensory conditioned pole-climb avoidance response task. Body weight and rectal temperatures were also recorded.

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
One animal at 218 mg/kg, two animals at 346 mg/kg and one animal at 550 mg/kg died during 2 to 9 weeks of study. The deaths were not dose-related and were not directly attributed to the test chemicals.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significant body weight reductions were observed at ≥218 mg/kg compared to control data.
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
After 15 weeks of dosing, the only neurobehavioral change was a dose-related decrease in hindlimb strength at ≥218 mg/kg. This effect persisted after 6 weeks of recovery.
Neuropathological findings:
effects observed, treatment-related
Description (incidence and severity):
After 15 weeks of dosing, the only neurobehavioral change was a dose-related decrease in hindlimb strength at ≥218 mg/kg. This effect persisted after 6 weeks of recovery.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 138 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
mortality
body weight and weight gain
behaviour (functional findings)
other: Neurobehavior
Remarks on result:
other: not specified
Dose descriptor:
LOAEL
Effect level:
<= 218 mg/kg bw/day (nominal)
Based on:
test mat. (total fraction)
Sex:
male
Basis for effect level:
body weight and weight gain
behaviour (functional findings)
Remarks on result:
other: not specified

Target system / organ toxicity

Critical effects observed:
not specified
System:
other: not specified

Applicant's summary and conclusion

Conclusions:
NOAEL for the test chemical was established at 138 mg/kg bw/day following five days of exposure per week, for 15 weeks in total, in male rats based on body weight changes and decrease hindlimb strength at ≥218 mg/kg
Executive summary:

The chemical was given to 9 to 10 male rats per dose level at 0 (vehicle control), 138, 218, 346 and 550 mg/kg by oral gavage, five days per week, for a total of 15 weeks. Prior to dosing, at 3-week intervals, and at 3 and 6 weeks after cessation of dosing, the rats were subjected to a battery of neurobehavioral tests including undifferentiated motor activity, forelimb and hindlimb grip strengths, rotation orientation, thermal sensitivity, startle responsiveness to acoustic and air-puff stimuli, and performance of a multisensory conditioned pole-climb avoidance response task. Body weight and rectal temperatures were also recorded. One animal at 218 mg/kg, two animals at 346 mg/kg and one animal at 550 mg/kg died during 2 to 9 weeks of study. The deaths were not dose-related and were not directly attributed to the test chemicals. Significant body weight reductions were observed at ≥218 mg/kg compared to control data.After 15 weeks of dosing, the only neurobehavioral change was a dose-related decrease in hindlimb strength at ≥218 mg/kg. This effect persisted after 6 weeks of recovery. NOAEL for the test chemical was established at 138 mg/kg bw/day following five days of exposure per week, for 15 weeks in total, in male rats based on body weight changes and decrease hindlimb strength at ≥218 mg/kg