Registration Dossier

Skin Irritation:

The skin irritation potential of 2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

2-bromoethanaminium bromide was estimated to be not irritating to the skin of White Russian rabbits.

Based on the estimated result 2-bromoethanaminium bromide (CAS No: 2576-47-8) can be considered to be not irritating to skin and can be classified under the category ˋnot classified’ as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated to be not irritating to the eyes of New Zealand Whiterabbits.

Based on the estimated result, 2-bromoethanaminium bromide (CAS No: 2576-47-8) can be considered to be not irritating to eyes and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR Toolbox 3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-bromoethanaminium bromide
- Molecular formula: C2H6BrNBrH
- Molecular weight: 204.892 g/mol
- Smiles notation: C(C[NH3+])Br.[BrH-]
- Inchl : 1S/C2H6BrN.BrH/c3-1-2-4;/h1-2,4H2;1H
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

other: White russian

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

Amount(s) applied: 0.5 g moistened with 0.25 ml water

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation were observed.

Estimation method: Takes mode value from the 7 nearest neighbours
Domain logical expression:Result: In Domain

((((((((((((((((("a" or "b" or "c" ) and ("d" and ( not "e") ) ) and ("f" and ( not "g") ) ) and ("h" and ( not "i") ) ) and ("j" and ( not "k") ) ) and ("l" and ( not "m") ) ) and "n" ) and ("o" and ( not "p") ) ) and "q" ) and ("r" and ( not "s") ) ) and ("t" and ( not "u") ) ) and ("v" and ( not "w") ) ) and "x" ) and ("y" and ( not "z") ) ) and "aa" ) and "ab" ) and ("ac" and "ad" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium Ion Formation >> Mustards by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group OR SN2 >> Acylation involving a leaving group >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Organic disulfides OR Low reactive OR Low reactive >> Primary haloalkanes OR Moderate reactive OR Moderate reactive >> Mono-methacrylic acid esters by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Miscellaneous Alkyl 2-halo alkenoates (SN2) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-bromoalkanoates (SN2) by Protein binding potency

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Amine oxides (Less susceptible) No Rank by Repeated dose (HESS)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic ring opening on aziridinium ion intermediate of N-mustards OR SN2 >> Nucleophilic ring opening on aziridinium ion intermediate of N-mustards >> Nitrogen Mustard by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Discrete chemical AND Dissociating chemical by Substance Type ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) OR Nonionic Surfactants by US-EPA New Chemical Categories

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.86

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.65

Interpretation of results:

not irritating

Conclusions:

2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated to be not irritating to the skin of White Russian rabbits

Executive summary:

The skin irritation potential of 2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

2-bromoethanaminium bromide was estimated to be not irritating to the skin of White Russian rabbits.

Based on the estimated result 2-bromoethanaminium bromide (CAS No: 2576-47-8) can be considered to be not irritating to skin and can be classified under the category ˋnot classified’ as per CLP regulation

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR Toolbox 3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

ediction was done using OECD QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-bromoethylammonium bromide
- Molecular formula: C2H6BrN.BrH
- Molecular weight: 204.892 g/mol
- Substance type: Organic
- Physical state: Solid
-Smiles: C(C[NH3+])Br.[BrH-]
-InChI: 1S/C2H6BrN.BrH/c3-1-2-4;/h1-2,4H2;1H

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

Amount(s) applied (volume or weight with unit): 0.07 g

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1 h, 24 h, 48 h, 72 h

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irrirtating effcts were observed.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain

(((((((((((((((("a" or "b" or "c" ) and ("d" and ( not "e") ) ) and ("f" and ( not "g") ) ) and ("h" and ( not "i") ) ) and ("j" and ( not "k") ) ) and ("l" and ( not "m") ) ) and "n" ) and "o" ) and "p" ) and "q" ) and ("r" and ( not "s") ) ) and ("t" and ( not "u") ) ) and ("v" and ( not "w") ) ) and ("x" and ( not "y") ) ) and "z" ) and ("aa" and "ab" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium Ion Formation >> Mustards by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group OR SN2 >> Acylation involving a leaving group >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Organic disulfides OR Low reactive OR Low reactive >> Primary haloalkanes OR Moderate reactive OR Moderate reactive >> Mono-methacrylic acid esters by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Miscellaneous Alkyl 2-halo alkenoates (SN2) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-bromoalkanoates (SN2) by Protein binding potency

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Halogenated Cycloalkane Type Compounds by Oncologic Primary Classification

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Low gene expression OR Low gene expression >> Ethylenediamine by Keratinocyte gene expression

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Known precedent reproductive and developmental toxic potential OR Not covered by current version of the decision tree OR Organophosphorus compounds (1b) by DART scheme v.1.0

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.09

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= -2.08

Interpretation of results:

other: not irritating

Conclusions:

2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

2-bromoethanaminium bromide (CAS No: 2576-47-8) was estimated to be not irritating to the eyes ofNew Zealand White rabbits.

Based on the estimated result, 2-bromoethanaminium bromide (CAS No: 2576-47-8) can be considered to be not irritating to eyes and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation:

In different studies, 2-bromoethanaminium bromide has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its closely related read across substances, Ethylenediaminetetraacetic acid [CAS: 60-00-4] and Trimethylamine hydrochloride [CAS: 593-81-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for2 -bromoethanaminium bromide. 2-bromoethanaminium bromidewas not irritating to the skin of White Russianrabbits.

This result is supported by the experimental study summarized in GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017; for the closely related substance, Ethylenediaminetetraacetic acid [CAS: 60-00-4]. The skins of rabbits were exposed to the test chemical at concentration of 50% in aqueous solution and skin reactions were observed up to 20 days. No known signs of irritation were observed after 20 days. Hence, Ethylenediaminetetraacetic acid (CAS No: -60-00-4) was considered to be not irritating to the rabbits skin.

In an another study summarized in IUCLID dataset, 2000 for the closely related substance, Ethylenediaminetetraacetic acid [CAS: 60-00-4], 50% of test chemical in aqueous solution was applied on the back skin of rabbits. The reaction time was 1; 5 and 15 minutes and 20 hours. Observations were made 24 hours and 8 days after application. Ethylenediaminetetraacetic acid [EDTA] failed to elicit any skin reactions after 8 days. Thus, ethylenediaminetetraacetic acid(CAS No: -60-00-4) was considered to be not irritating to the rabbits skin.

The above results are further supported by experimental study summarized in IUCLID dataset, 2000; for the closely related substance, Trimethylamine hydrochloride[CAS: 593-81-7].The study was performed according to BASF test. Trimethylamine hydrochloride was applied to the skin of rabbits and signs of irritation were observed (duration and dose not mentioned).No known signs of irritation were observed. Hence, Trimethylamine hydrochloride (CAS No:- 593-81-7) was considered to be not irritating to the skin of rabbits.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 2-bromoethanaminium bromide can be considered to be not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, 2-bromoethanaminium bromide has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its closely related read across substances, Arginine [CAS: 74-79-3]and Trimethylamine hydrochloride [CAS: 593-81-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for2 -bromoethanaminium bromide. 2-bromoethanaminium bromidewas not irritating to the eyes of New Zealand Whiterabbits.

This result is supported by the experimental study summarized in EFSA Journal 05 January 2016; 14(1):4345, for the closely related substance, Arginine [CAS: 74-79-3]. The study was performed in accordance with OECD guideline 405. Arginine was installed (single installation) in the conjunctival sac of Himalayan rabbits at concentration of 100mg/animal for1 h exposure or subsequently. Arginine did not cause any changes in the rabbit eyes after 1 hour. Hence, Arginine(CAS No: - 74-79 -3) was considered to be not irritating to the rabbits’ eye.

The above results are further supported by experimental study summarized in IUCLID dataset, 2000; for the closely related substance, Trimethylamine hydrochloride[CAS: 593-81-7].The study was performed according to BASF test. Trimethylamine hydrochloride was instilled in to the eyes of rabbits and signs of irritation were observed (duration and dose not mentioned).No known signs of irritation were observed. Hence, Trimethylamine hydrochloride (CAS No:- 593-81-7) was considered to be not irritating to the eyes of rabbits.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 2-bromoethanaminium bromide can be considered to be not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Available studies for 2-bromoethanaminium bromide indicate that it is not likely to any cause irritation to skin and eyes.

Hence, 2-bromoethanaminium bromide can be classified under the category “Not Classified” for eyes and skin as per CLP regulation.