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Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Justification for type of information:
A read-across approach is applied between Reaction products of monoethanolamine and boric acid (1:1) and Reaction products of monoethanolamine and boric acid (1:3) for the human health endpoints due to the structural similarity of the two reaction products (Scenario 6 in ECHA’s RAAF document), both resulting from the same starting materials (only the ratio is different), and through the same manufacturing process.
Commercial MEA Polyborate products are commonly formulated at either 1:1 or 1:3 mole ratios of MEA to boric acid, or sometimes at ratios in between. All compositions in this range contain equilibrium mixtures of the exact same chemical species, but with somewhat different population distributions.
The existing physico-chemical, toxicological, environmental fate and ecotoxicological data already showed good correlation with no significant differences between the two ratios.

The results of the newly commissioned, additional anchoring studies (water solubility, vapour pressure and octanol-water coefficient, Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assays, acute toxicity studies via dermal route and oral route) showed good correlation between Reaction products of monoethanolamine and boric acid (1:1) and Reaction products of monoethanolamine and boric acid (1:3), and therefore further supported our category hypothesis.

Based on the lack of dermal irritation responses in the rabbit from dermal application of MEA Polyborate 1:3, no GHS classification for skin irritation is proposed for both 1:1 and 1:3 ratios. Three 0.5 ml doses of undiluted MEA Polyborate 1:3 were applied to the dorsum of a single New Zealand White rabbit. Each test site was covered by a gauze patch, which was removed after exposure periods of 3 minutes, one hour and four hours. Dermal reactions were assessed immediately after removal of each dressing. All dermal sites were re-assessed 24, 48 and 72 hours after removal of the last dressing. No dermal irritation was observed at any of the three sites or time periods (Covance 1998b). In addition, in vitro and in vivo eye irritation studies are available on both ratios, and show correlation with only slight difference, i.e. MEA Polyborate 1:1 is not irritating in an in vivo eye irritation study, whilst MEA Polyborate 1:3 is moderately irritating.
On this basis MEA Polyborate 1:1 is considered not to be an irritant to skin.
Category: MEA Polyborates
GLP compliance:
yes (incl. certificate)
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
0.3
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Irritant / corrosive response data:
1 hour observation
Rabbit number Erythema Oedema Comments
660 0 0 None
677 0 0 None
678 1 0 None
24 hour observation
Rabbit number Erythema Oedema Comments
660 0 0 None
677 0 0 None
678 1 0 None
48 hour observation
Rabbit number Erythema Oedema Comments
660 0 0 None
677 0 0 None
678 0 0 None
72 hour observation
Rabbit number Erythema Oedema Comments
660 0 0 None
677 0 0 None
678 0 0 None

Other effects:
none

Mean scores for erythema and oedema (calculated from the values recorded at the 24,48 and 72 hour readings) were used.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the criteria described in EEC Commission Directive 91/325/EEC of 1st March 1991, MEA Polyborate 1:1 is not classified for skin irritation/corrosion. Based on the justification in the field ' Justification for type of information', this results is applicable for MEA Polyborate 1:3.
Executive summary:

The purpose of this study was to assess the degree of irritation produced by the test article when applied to the skin of the albino rabbit. The procedures e used were in accordance with EEC Annex V guidelines.

A 0.5 aliquot of the test article was applied over a previously clipped area of about 6 sq cm of the dorsal skin of each of 3 albino rabbits. The test article was held in contact with the skin, under a semi-occlusive patch assembly, for a 4 hour period. The patches were then removed and skin reaction assessed after one, 24, 48 and 72 hours.

The treated site on 2 of the 3 rabbits remained free from apparent irritation throughout the 72 hour observation period. A barely perceptable erythema was noted at the treated site on the third animal one and 24 hours after patch removal but was no longer apparent at the 48 and 72 hour examinations.

The test article did not produce significant irritation in any animal.

According to the criteria described in EEC Commission Directive 91/325/EEC of 1st March 1991, MEA Polyborate 1:1 is not classified for skin irritation/corrosion. Based on the justification in the field ' Justification for type of information', this results is applicable for MEA Polyborate 1:3.

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

Eye irritation

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Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
other: Bovine corneal opacity and permeability test (BCOP test)
GLP compliance:
yes (incl. certificate)
Species:
other: bovine
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
750 microlitres
Duration of treatment / exposure:
10 minutes
Observation period (in vivo):
10 minutes
Number of animals or in vitro replicates:
not applicable
Irritation parameter:
cornea opacity score
Remarks:
mean
Value:
0
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Remarks:
mean
Value:
0
Negative controls validity:
valid
Positive controls validity:
valid

Table1            Summary of opacity, permeability andin vitroscores

 

Treatment

Mean

Opacity1

Mean

Permeability1

MeanIn vitroIrritation Score1, 2

Negative control

0

0.000

0

Positive control

(Benzalkonium Chloride)

82

4.144

144

MEA Polyborate 1:1

0

-0.001

0.0

 

1     Calculated using the negative control mean opacity and mean permeability values.

2     In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490value).

 

Interpretation of results:
other: not severe irritant or corrosive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
MEA Polyborate 1:3 is not severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report.
Executive summary:

Screening for the eye irritancy potential of MEA Polyborate 1:3 using the Bovine Corneal Opacity and Permeability test (BCOP test).

 

This summary describes the ocular irritation properties of MEA Polyborate 1:3 on an isolated bovine cornea. The possible ocular irritancy of MEA Polyborate 1:3 was tested through topical application for 10 ± 1 minutes.

 

Batch EU-01696 of MEA Polyborate 1:3 was a clear colourless liquid with a purity of 68% salt in water. The test substance was applied as it is (750 µl) directly on top of the corneas.

 

The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 144 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

 

MEA Polyborate 1:3 did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 0.0 after 10 minutes of treatment.

 

Finally, it is concluded that this test is valid and that MEA Polyborate 1:3 is not severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report.

 

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March - April 1998
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline followed
Principles of method if other than guideline:
To determine the irritancy or corrosive effect of the particular chemical by the single installation into the cinjunctival sac of a rabbit to permit the estimation of the hazard it presents to man in the event of inadvertant contamination of the eye.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Charle River Uk Ltd, Margate, U.K.
- Age at study initiation:
- Weight at study initiation: 3.63 kg
- Housing:Individually housed in floor pens
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):16-22 deg. C
- Humidity (%):40-80%
- Air changes (per hr):10
- Photoperiod (hrs dark / hrs light):12/12

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 ml
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Observation period (in vivo):
1,4,24,48,72 hours after treatment
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done
- Time after start of exposure: Not done

SCORING SYSTEM:
TOOL USED TO ASSESS SCORE: visual or by biomicroscope
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: not given
Score:
ca. 0
Reversibility:
fully reversible within: two days
Remarks on result:
other: Other data (time point, scoring)not available in the report
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
other: one animal only
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not documented
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Remarks on result:
other: not documented
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Single ocular administrations of MEA Polyborate 1:3 135 g/L resulted in only minor reversible irritation reactions of the conjunctivae. The cornea and iris remained overtly unaffected by installation of the test article.
Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit.

A single installation of the test material to the left conjunctival sac of one rabbit produced a moderate sting reaction.

Injection of the conjunctival blood vasculature, slight chemosis and a moderate ocular discharge. This conjunctival irritation persisted at examinations undertaken one half hour and one hour after dosing. Resolution of the conjunctival irritation had commenced four hours after dosing and was complete two days after.The cornea and iris remained overtly unaffected by installation of MEA Polyborate 1:3 135 g/L.

Applied fluoroscein was not absorbed into the cornea at either the 24 hour or 48 hour examinations.

Single ocular administrations of MEA Polyborate 1:3 135 g/L resulted in only minor reversible irritation reactions of the conjunctivae. The cornea and iris remained overtly unaffected by installation of the test article.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin irritation:

In a GLP study according to EEC Commission Directive 91/325/EEC of 1st March 1991, MEA Polyborate 1:1 is not irritating to New Zealand White rabbits. This result is considered applicable for MEA Polyborate 1:3 based on the justification elaborated in the endpoint study record and in the Category Justification Document.

Eye irritation:

Single ocular administrations of MEA Polyborate 1:3 135 g/L resulted in only minor reversible irritation reactions of the conjunctivae. The cornea and iris remained overtly unaffected by installation of the test article.

MEA Polyborate 1:3 is not severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report.