Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

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

Constituent 1
Chemical structure
Reference substance name:
Sodium salicylate
EC Number:
200-198-0
EC Name:
Sodium salicylate
Cas Number:
54-21-7
Molecular formula:
C7H6O3.Na
IUPAC Name:
sodium salicylate
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:
behaviour (functional findings)
body weight and weight gain
mortality
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:
behaviour (functional findings)
body weight and weight gain
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