Sodium salicylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

data is from study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Acute dermal toxicity test was carried out to study the effects of test chemical on rats.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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 (IUPAC name): Sodium salicylate
- Common name: Monosodium salicylate
- Molecular formula: C7H6O3.Na
- Molecular weight: 160.1035 g/mol
- Smiles notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- InChl: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1
- Substance type: Organic

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-House Bred
- Age at study initiation: Healthy young adult were used.Females were nulliparous and non pregnant.
- Weight at study initiation: Male: Minimum: 218 g and Maximum: 261 g
(Prior to Treatment) Female:Minimum: 210 g and Maximum: 221 g
- Housing: Bedding : All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 25/2014
Husbandry : The animals were housed individually in polycarbonate cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum): animals were provided conventional laboratory rodent diet ad libitum
- Water : Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: All animals were acclimatized to the test conditions for 6 days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.90 °C Maximum: 23.30 °C
- Humidity (%): Minimum: 52.30% Maximum: 66.50%
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: Approx. 10% of body surface area of rat
- Type of wrap if used: porous gauze dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by using distilled water
- Time after start of exposure: 24-hour exposure period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 ml

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

total:10 animals
2000 mg/kg bw:male 5 and female:5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period for clinical signs, teice daily for mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

no data available

Results and discussion

Preliminary study:

no data available

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period

Clinical signs:

other: All the animals were observed with normal clinical signs throughout the experimental period

Gross pathology:

The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Other findings:

no data available

Any other information on results incl. tables

Individual Animal Body Weight (g) andBody Weight Changes(%)

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.	Sex	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	Male	222	232	248	4.50	11.71
2		237	243	256	2.53	8.02
3		261	279	314	6.90	20.31
4		255	276	297	8.24	16.47
5		218	229	232	5.05	6.42
6	Female	214	231	244	7.94	14.02
7		212	222	228	4.72	7.55
8		221	237	253	7.24	14.48
9		210	222	241	5.71	14.76
10		213	220	232	3.29	8.92

Individual Animal Clinical Signs and Symptoms

Dose:2000 mg/kg body weight

Animal No.	Sex	Hour(s) - Day 0				Day
		1	2	3	4	1	2	3	4	5	6	7
1	Male	1	1	1	1	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1	1	1	1	1
3		1	1	1	1	1	1	1	1	1	1	1
4		1	1	1	1	1	1	1	1	1	1	1
5		1	1	1	1	1	1	1	1	1	1	1
6	Female	1	1	1	1	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1	1	1	1	1
8		1	1	1	1	1	1	1	1	1	1	1
9		1	1	1	1	1	1	1	1	1	1	1
10		1	1	1	1	1	1	1	1	1	1	1

 

Animal No.	Sex	Day
		8	9	10	11	12	13	14
1	Male	1	1	1	1	1	1	1
2		1	1	1	1	1	1	1
3		1	1	1	1	1	1	1
4		1	1	1	1	1	1	1
5		1	1	1	1	1	1	1
6	Female	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1
8		1	1	1	1	1	1	1
9		1	1	1	1	1	1	1
10		1	1	1	1	1	1	1

Key: 1 = Normal

Individual Animal Mortality Record

 Dose:2000 mg/kg body weight

Animal No.	Sex	Days of Observation (0 to 14)
		Morning Observations	Evening Observations
1	Male	No mortality and morbidity	No mortality and morbidity
2		No mortality and morbidity	No mortality and morbidity
3		No mortality and morbidity	No mortality and morbidity
4		No mortality and morbidity	No mortality and morbidity
5		No mortality and morbidity	No mortality and morbidity
6	Female	No mortality and morbidity	No mortality and morbidity
7		No mortality and morbidity	No mortality and morbidity
8		No mortality and morbidity	No mortality and morbidity
9		No mortality and morbidity	No mortality and morbidity
10		No mortality and morbidity	No mortality and morbidity

Summaryof Animal Body Weight (g) and Body Weight Changes (%)

Dose:2000 mg/kg body weight

Sex		Body Weight (gram)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
Male	Mean	238.60	251.80	269.40	5.44	12.59
	SD	19.19	24.06	34.59	2.20	5.80
	n	5	5	5	5	5
Female	Mean	214.00	226.40	239.60	5.78	11.95
	SD	4.18	7.30	9.91	1.88	3.43
	n	5	5	5	5	5

Keys:SD= Standard deviation, n = Number of animals

GrossNecropsyObservation

 Dose:2000 mg/kg body weight                                               Mode of Death:Terminal Sacrifice

Animal No.	Sex	Gross Observation
		External	Internal
1	Male	No abnormality detected	No abnormality detected
2		No abnormality detected	No abnormality detected
3		No abnormality detected	No abnormality detected
4		No abnormality detected	No abnormality detected
5		No abnormality detected	No abnormality detected
6	Female	No abnormality detected	No abnormality detected
7		No abnormality detected	No abnormality detected
8		No abnormality detected	No abnormality detected
9		No abnormality detected	No abnormality detected
10		No abnormality detected	No abnormality detected

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Executive summary:

Acute dermal toxicity study was conducted as per OECD No.402 by using the given test chemical in Wistar Rats. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test chemical moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1 - 14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were recorded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. All the animals were observed with normal clinical signs throughout the experimental period. In males and females, mean body weight was observed with gain on day 7 and 14, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Under the conditions of this, the LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).