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Description of key information

Bis[(2-hydroxyethyl)ammonium] sulfite is a skin irritant but no eye irritant based on reliable in vivo study results available for the target chemical.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable non-GLP study, comparable to guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not applicable
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Before OECD Guideline 404 was first adopted in 1981, skin irritation was tested using a BASF test.
The methods were based on Draize (Federal Register 38, No. 187, § 1500.41, p. 27019 (1973-09-27)).
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
occlusive
Preparation of test site:
other: intact abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: approximately 1 mL (not indicated in the report; standard volume used in the BASF test)
Duration of treatment / exposure:
5 minutes, 2 hours
20 hours
Observation period:
8 days
Number of animals:
2 rabbits (5 minutes, 2 hours)
3 rabbits (20 hours)
Details on study design:
TEST SITE
- Area of exposure: back (2.5 cm × 2.5 cm)

SCORING SYSTEM:
BASF scheme
Irritation parameter:
erythema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: superficial necrosis after 8 days; tested on intact skin
Irritation parameter:
erythema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/72 hours
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: scaling after 8 days; tested on intact skin
Irritation parameter:
erythema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/72 hours
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: scaling after 8 days; tested on intact skin
Irritation parameter:
edema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/72 hours
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: tested on intact skin
Irritation parameter:
edema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: tested on intact skin
Irritation parameter:
edema score
Remarks:
(20-hour exposure)
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/72 hours
Score:
2.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: tested on intact skin
Irritant / corrosive response data:
Test on intact skin, 20-hour application (key information):
The key results are summarised in the irritation/corrosion results table (see above).
The mean erythema score (24/72 hours) was ≥ 2.5 in 3/3 rabbits. Findings were not fully reversibe in 3/3 rabbits within the observation period of 8 days. At the end of the observation period, superficial necrosis, which in contrast to full thickness necrosis represents an indicator for strong irritancy, was noted in 1/3 rabbits and scaling was observed in 2/3 rabbits.
The mean edema score (24/72 hours) was 2.5 in 2/3 rabbits. Findings were not fully reversible in 1/3 rabbits.

Test on abraded (scarified skin), 20-hour application (supporting information):
The mean erythema score (24/72 hours) was 4 in 3/3 rabbits. Necroses indicative of strong irritancy were seen at the 24- and 72-hour readings and at the end of the 8-day observation period in all rabbits.
The mean edema score (24/72 hours) was ≥ 2.5 in 3/3 rabbits. The findings were not reversible within 8 days.

Short-term test (supporting information):
No findings were noted in 2/2 rabbits (24/48 hours) following exposure for 5 min. Exposure for 2 hours resulted in a mean erythema score of 0.5 and no edema in one rabbit, and in a mean erythema score of 2 and a mean edema score of 0.5 in the remaining rabbit. These findings were fully reversible within 8 days.
Other effects:
None

A primary irritation score of 5.8 was calculated (under consideration of the test results for intact plus abraded skin). The test item was considered to be a moderate irritant based on this score.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable non-GLP study, comparable to guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not applicable
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Principles of method if other than guideline:
Before OECD Guideline 405 was first adopted in 1981, eye irritation was tested using a BASF test.
The methods were based on Draize (Federal Register 38, No. 187, § 1500.42, p. 27019 (1973-09-27)).
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 50 µL (not indicated in the report; standard volume used in the BASF test)
Duration of treatment / exposure:
single treatment
Observation period (in vivo):
not reported (the standard duration of the observation period in the BASF test on eye irritation was 7 or 8 days)
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
SCORING SYSTEM:
Draize scoring system
Based on the Draize scores, a primary irritation index was calculated (max. score: 110/9).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/48/72 hours
Score:
1
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: scores: 1/1/1
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/48/72 hours
Score:
1
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: scores: 1/1/1
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/48/72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: scores: 1/1/0
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(animal #1)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(animal #2)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(animal #3)
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Slight conjunctival redness was the only test item-related finding noted. The mean scores (24/48/72 hours) for this endpoint were 1 in 2/3 rabbits and 0.7 in the remaining rabbit. Reversibility was not reported; however, 1/3 rabbits showed no signs of conjunctival redness at the 72-hour reading.
The primary irritation index was calculated to be 1.8.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

In a primary skin irritation study (BASF AG, 1980; 78/823), Vienna White rabbits were dermally exposed to approximately 1 mL of undiluted Kauraminhärter CE 5196 flüssig, i.e. Bis[(2 -hydroxyethyl)ammonium] sulfite, for 5 minutes or 2 hours (short-term test, supporting information) and for 20 hours using abraded skin (supporting information) or intact skin (key information, irritation scored at 24/72 hours). Animals then were observed for 8 days.

In the key study, i.e. after 20 -hour exposure of intact skin, the mean erythema score (24/72 hours) was ≥ 2.5 in 3/3 rabbits. Findings were not fully reversibe in 3/3 rabbits within the observation period. At the end of the observation period, superficial necrosis, which in contrast to full thickness necrosis represents an indicator for strong irritancy, was noted in 1/3 rabbits and scaling was observed in the 2 remaining rabbits. The mean edema score (24/72 hours) was 2.5 in 2/3 rabbits. Edema were not fully reversible in 1/3 rabbits. No or less severe findings were noted following short-tem exposure (supporting data): There were no findings in 2/2 rabbits (24/48 hours) following exposure for 5 min, while exposure for 2 hours resulted in a mean erythema score of 0.5 and no edema in one rabbit, and in a mean erythema score of 2 and a mean edema score of 0.5 in the remaining rabbit with full reversibility. Under the conditions of this study, and with special regard to the long exposure duration of 20 hours in association with the use of occlusive dressings, the test item was considered to be a skin irritant.

A direct read-across assessment is not considered applicable for the endpoint skin irritation/corrosion. Supporting studies in Vienna White rabbits conducted by means of the same method (similar to OECD 404) with 2 -Aminoethanol and Methylethanolamin revealed corrosive properties (BASF AG, 1966; XV/305; BASF AG, 1981; 79/561). These corrosive properties of them might trigger the irritant response observed for Bis[(2 -hydroxyethyl)ammonium] sulfite. As evidenced by reliable supporting data the source chemical Sodium sulfite (BASF AG, 1981; 81/311) showed no skin irritating/corrosive properties.

Eye irritation

In a primary eye irritation study (BASF AG, 1980; 78/823), 50 µL of undiluted Kauraminhärter CE 5196 flüssig, i.e. Bis[(2 -hydroxyethyl)ammonium] sulfite, was instilled into the conjunctival sac of each one eye of 3 Vienna White rabbits. Irritation was scored by the method of Draize at 24, 48 and 72 hours. Slight conjunctival redness was the only test item-related finding noted. The mean scores (24/48/72 hours) for this endpoint were 1 in 2/3 rabbits and 0.7 in the remaining rabbit. Reversibility was not addressed in the study; however, 1/3 rabbits showed no signs of conjunctival redness at the 72 -hour reading indicating reversibility. Under the conditions of this study, the test item was no eye irritant.

A direct read-across assessment is not considered applicable for the endpoint eye irritation. Supporting study data indicated that 2 -Aminoethanol (BASF AG, 1966; XV/305) with a pH value of 12, Methyaminoethanol with a pH value of 13.6, and Disodium disulfite (BASF AG, 1984; 84/200) with a pH value range of 3.5 -5 have the potential to damage rabbit eyes seriously and irreversibly. This finding is considered largely related to acid/alkaline properties of these substances and thus not applicable for Bis[(2 -hydroxyethyl)ammonium] sulfite, as evidenced by the key study results.

Respiratory irritation

No experimental data are available on respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
The key study was selected for the assessment of the skin irritation / corrosion hazard since it provides reliable data on the target chemical.

Justification for selection of eye irritation endpoint:
The key study was selected for the assessment of the eye irritation hazard since it provides reliable data on the target chemical.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The key study results obtained for the test item Bis[(2 -hydroxyethyl)ammonium] sulfite in reliable in vivo studies are relevant for classification. Based on these studies, Bis[(2 -hydroxyethyl)ammonium] sulfite is subject to classification as a skin irritant with Xi; R38 and Category 2; H315 according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (GHS/CLP), respectively.

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