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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Repeated dose oral toxicity study of the test chemical
Author:
Wooles et al
Year:
1967
Bibliographic source:
Toxicology And Applied Pharmacology

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Repeated dose oral toxicity study was performed to determine the toxic nature of sodium salt of salicylic acid
GLP compliance:
not specified
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
Specific details on test material used for the study:
- Name of test material :sodium salicylate
- Molecular formula : C7H6O3.Na
- Molecular weight : 160.1035 g/mol
- Substance type: organic
- Physical state: solid
- Smilies notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- Inchi: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1

Test animals

Species:
rat
Strain:
other: Albino
Details on species / strain selection:
No data
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Holtzman Company, Madison, Wisconsin.
- Age at study initiation: No data
- Weight at study initiation: 160-200 g
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): Ground laboratory diet
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
No data
Vehicle:
physiological saline
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test chemical was dissolved in saline at dose level of 0 or 300 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Saline
- Concentration in vehicle: 0 or 300 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
7 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
0 or 300 mg/Kg/day
No. of animals per sex per dose:
Total: 11
0 mg/kg/day: 5 males
300 mg/Kg/day: 6 males
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: After 7 days treatment
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Plasma free fatty acid levels and liver and plasma triglyceride levels were determined.

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: 16 hrs prior to termination
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, liver weight was measured
HISTOPATHOLOGY: No data
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
No change in plasma FFA levels was observed 90 minutes after the last of 7 daily administrations of salicylate. Similarly, liver and plasma triglyceride levels of salicylate-treated animals were comparable to those of the saline-treated control group.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Liver weight was unaffected was
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No significant effects were noted at the mentioned dose level

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table: Effect Of Seven Successive Daily Oral Doses Of 300 Mg/Kg Of Salicylic Acid (As Sodium Salicylite) On Plasma Free Fatty Acids And Liver And Plasma Triglyceride Concentrations

Treatment

No. of rats

Liver weight (%)

Triglyceride concentration

Plasma FFA (µeq/L)

Liver (mg/g)

Plasma (mg/100 mL)

Control

5

3.64 ± 0.10

8.8 ± 1.3

28 ± 1

463 ± 62

Saline

6

385 ± 0.12

10.6 ± 1.0

26 ± 4

316 ± 33

 

Applicant's summary and conclusion

Conclusions:
The no observed adverse effect level (NOAEL) for male rats is considered to be 300 mg/Kg/day when they were treated orally and repeatedly for 7 days with sodium salicylate.
Executive summary:

Repeated dose oral toxicity study was performed to determine the toxic nature of sodium salt of salicylic acid. The test chemical was dissolved in saline at dose level of 0 or 300 mg/kg/day and fed by the oral intubation route of exposure fr 7 days to male albino rats. The rats were killed 1 hrs after the last of 7 daily administrations. The animals were observed for clinical chemistry parameters including liver and plasma lipids and triglyceride and free fatty acid. No change in plasma FFA levels was observed 90 minutes after the last of 7 daily administrations of salicylate. Similarly, liver and plasma triglyceride levels of salicylate-treated animals were comparable to those of the saline-treated control group. Based on the observations made, no observed adverse effect level (NOAEL) for male rats is considered to be 300 mg/Kg/day when they were treated orally and repeatedly for 7 days with sodium salicylate.