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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Description of key information

For skin irritation, a GLP guideline study (RCC, 2008) has been chosen as key study. Results show that salicylic acid does not elicit any skin reactions at the application site at any of the observation times. A study of lower reliability (Bio-fax, 1971) has been chosen as supporting study. These studies show that salicylic acid is not a primary skin irritant. A human patch test (Berner, 1989) showed slight irritation.
For eye irritation, a publication by Sugai et al. (1991) has been chosen as key study. Salicylic acid induced severe irritation not recovering within 21 days of treatment. A similar result was obtained in a supporting study (Bio-Fax, 1971) These studies indicate that salicylic acid is a severe eye irritant.
No specific study has been carried out on respiratory irritation. Data from an acute toxicity study and worker experience suggest that high dust levels cause slight irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 AVRIL 2008 to 28 MAY 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study, without any deviation from the guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan france SARL
- Age at study initiation: 12 weeks (male) / 12-13 weeks (females)
- Weight at study initiation: 2452 g (male), 2287 and 2295 g (females)
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): pelleted standard rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): community tap water ad libitum
- Acclimation period: 4 or 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23°C
- Humidity: 30-70% (above 70% during cleaning process)
- Air changes (per hr): 10-15
- Photoperiod: 12 hours light and 12 hours dark

IN-LIFE DATES: From: 07/04/2008 To: 22/04/2008
Type of coverage:
semiocclusive
Preparation of test site:
other: electric clipped
Vehicle:
other: moistened with purified water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test substance applied, with 0.5 mL purified water
Duration of treatment / exposure:
4 hours
Observation period:
skin reaction assessed at 1, 24, 48 and 72 hours, and 7, 10, 14 days after exposure (after the removal of the patch)
Number of animals:
a single animal first (to assess the irritancy of the substance) and then 2 remaining animals
Details on study design:
TEST SITE
- Area of exposure: left flank of the animal
- % coverage: ca. 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch held in contact with the skin with an adhesive hypoallergenic aerated semi occlusive dressing and restrainer bandage wrapped around the abdomen

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm tap water
- Time after start of exposure: just after 4 hours exposure

SCORING SYSTEM: according to the Directive 2004/73/EC
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
no skin reaction at any of the observation times, for the 3 animals
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, salicylic acid is not irritating according to the Directive 2004/73/EC and to the GHS, second Revised Edition, 2007.
Executive summary:

In a primary dermal irritation study, young adult New Zealand White rabbits (1 male and 2 females) were dermally exposed to 0.5 g of salicylic acid moistened with 0.5 mL purified water. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 14 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately.
The test item did not elicit any skin reactions at the application site at any of the observation times, all scores = 0. The individual mean score for erythema/ eschar and oedema for each of the 3 animals was 0.
Based upon the directive 2004/73/EC and the GHS classification, acid salicylic is considered as not irritating to the rabbit skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The method is in accordance with recognized test guideline. The test conditions and the results are detailed, but there is no information about the purity of the test substance.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Draize Test
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Takeo breeder (Shizuka, Japan)
- Age at study initiation: no data
- Weight at study initiation: 2.0-2.2 kg
- Housing: in metal cages (39x40x44 cm)
- Diet: RC4 diet (Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum.
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25+/-1 °C
- Humidity (%): 55 +/- 5 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: right eye
Amount / concentration applied:
Amount applied: 100 mg
Duration of treatment / exposure:
unwashed
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize method (Maximum value of Draize score for cornea, conjunctiva and iris was 80, 20 and 5, respectively)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: not applicable
Score:
ca. 54.1
Max. score:
80
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Draize score : The sum of value recorded for cornea was divided by the number of observation times
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: not applicable
Score:
10.3
Max. score:
20
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Draize score: The sum of values was divided by the number of observation times.
Irritation parameter:
iris score
Remarks on result:
not determinable
Remarks:
could not be determined because of the corneal opacity
Irritation parameter:
chemosis score
Remarks on result:
other: no data available
Irritant / corrosive response data:
The raw data for each individual animal at each observation time up to removal of each animal from the test were not available.
Iris score was not evaluted due to corneal opacity.
Other effects:
Nothing was reported.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Salicylic acid induced severe irritation not recovering within 21 days of  treatment. Salicylic acid is therefore classified irritant for the
eyes, with R41: risk of serious damage to eyes, according to EU criteria and is classified category 1 (irreversible effects on the eye) according to the GHS (EU).
Executive summary:

In an eye irritation study (Sugai et al., 1991), 100 mg of salicylic acid were placed into the conjunctival sac of the left eye of female white rabbits, the right one being kept as control. The eyes were examined and the grade of ocular reaction was recorded at 1, 4, 24, 48, 72, 96 hr and 7, 14 and 21 days after administration. Corneal opacity, erythema, chemosis, secreta and iritis were classified according to the Draize method. The sum of values, recorded for cornea, conjunctiva and iris, was divided by the number of observation times and the average scores were used as the grade of eye irritation potential. Results showed that salicylic acid induced severe irritation not recovering within 21 days of treatment.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation:

Two valid unpublished study reports in rabbits are available for evaluation of this endpoint. The GLP study (RCC, 2008) following the OECD guideline 404, classified 1 (valid without restriction), has been chosen as key study. Results show that salicylic acid does not elicit any skin reactions at the application site at any of the observation times. The other study report (Bio-fax, 1971), classified 2 (valid with restriction) has been chosen as supporting study. This study consists of a Draize test, not following current guidelines. Results indicate that salicylic acid under the conditions of this test is also not considered to be a skin irritant. A human patch test (Berner, 1989) showed SA to cause slight irritation.Taken together these results show that salicylic acid is not a significant skin irritant.

Eye irritation:

Three in vivo studies (Rel 2) are available for evaluation of this endpoint. The publication by Sugai et al. (1991) has been chosen as key study.The primary eye irritation potential of salicylic acid was evaluated according to Draize method. Under the conditions of this study, salicylic acid induced severe irritation not recovering within 21 days of treatment. Draize scores for cornea and conjunctivae were 54.1 and 10.3 respectively. In the study report (Bio-fax, 1971), chosen as supporting study, the primary eye irritation potential of salicylic acid was evaluated with a method similar to a Draize test. In this study, salicylic acid induced also severe irritation. Mean scores for cornea, iris and conjunctivae were 51.5, 40.3 and 38.7 at 24 hr, 48 hr and 72 hr respectively. A publication by Ohno et al (1999), a draize eye irritation test was conducted with sodium salicylate. Average scores at 24 hr after application for cornea, iris and conjunctiva were 21.7, 3.3 and 12.7 respectively. This study is also considered acceptable as a supporting study.

An in vitro BCOP test evaluated SA as part of a program to develop alternatives for in vivo eye irritation tests (Gautheron, 1992). Results for opacity but not permeability were reported for SA tested at up to 10%. With opacity readings: 0.1%: 7.2 +/- 1.7; 1%: 70.2 +/- 8.4; 5%: 88.2 +/- 5.1; 10%: 98.7 +/- 7.4, SA was considered a severe irritant.

Taken together the in vitro and in vivo results indicate that salicylic acid is a severe eye irritant.

Respiratory Irritation:

No specific study has been carried out on respiratory irritation. Data from an acute toxicity study suggest that very high dust levels may cause slight irritation. Human worker experience also indicates slight irritant effects.


Justification for selection of skin irritation / corrosion endpoint:
Key reliability 1 study

Justification for selection of eye irritation endpoint:
Key reliability 2 study

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation:

Not classified, Non-irritant according to EU DSD and GHS EU/UN criteria

Based on GLP study (RCC, 2008), OECD 404, Rel 1

Eye irritation:

Irritant (Xi) with R41 (risk of serious damage to eyes) according to EU DSD criteria. Category 1 (irreversible effects on the eye) according to GHS EU/UN. Based on threein vivostudies and oneinvitro study Rel. 2

Respiratory irritation:

Not classified, Non-irritant according to EU DSD and GHS EU/UN criteria

Based on only slight irritant effects in an acute inhalation toxicity study and from human experience.