Sodium salicylate

Repeated dose toxicity: oral

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

Reference

Reference 1

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 2

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

Test material information

Constituent 1

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

1

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

2

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