2-bromoethylammonium bromide

Endpoint summary

Description of key information

The skin sensitization potential of 2-bromoethanaminium bromide(2576-47-8) estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances 2-bromoethanaminium bromide(2576-47-8) was predicted to be not sensitizing to the skin of Dunkin-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 v3.4 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No data avaliable

Specific details on test material used for the study:

Name of test material (as cited in study report): 2-bromoethanaminium bromide
Molecular Formula: C2H6BrN.BrH
Molecular Weight: 204.892 g/mole
Smiles notation: C(C [NH3+]) Br. [BrH-]
Substance type: Organic
Physical state: not specified

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:Harlan Winkelmann, Gartenstrasse 27, D-33178 Borchen
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known:no data avaliable
- Age at study initiation:Approx. 4 - 7 weeks at the first application.
- Weight at study initiation:211 g to 389 g.
- Housing:Makrolon cages type III (23 cm x 39 cm bottom area, 18 cm height) with wire mesh lids, single caging. From Day 0: group caging in plastic containers (46 cm x 105 cm x 36 cm), partly shaded, 1 group per container.
- Diet (e.g. ad libitum):Altromin Maintenance Diet No. 3122, rich in crude fibers, ad libitum, offered in stainless steel containers.
- Water (e.g. ad libitum):Tap water offered in Makrolon bottles with stainless steel canules ad libitum.
- Acclimation period:4 days
- Indication of any skin lesions:no data avaliable

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Average of 22 °C, continuous control and recording
- Humidity (%): Average of 50.8 % in step 1, of 63.2 % in step 2; continuous control and recording.
- Air changes (per hr): Approx. 12/h.
- Photoperiod (hrs dark / hrs light):Only artificial light from 6.00 a.m. to 6.00 p.m.
- IN-LIFE DATES: From: To:

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50 % (w/w) in white petrolatum

Day(s)/duration:

Induction 1: 24hr and induction 2 :48hr

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

50 % (w/w) in white petrolatum

Day(s)/duration:

24 hr

No. of animals per dose:

Total:30
Test group:20
Control group:10

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Induction 1:24hr and induction 2 :48hr
- Test groups: 20
- Control group: 10
- Site: an area of approx. 2 cm x 4 cm in the interscapular region.
- Frequency of applications: on day1 and day 8
- Duration: Induction 1:24hr and induction 2 :48hr
- Concentrations: 50 % (w/w) in white petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 22
- Exposure period: 24hr
- Test groups: 20
- Control group: 10
- Site: the left flanks
- Concentrations: 50 % (w/w) in white petrolatum
- Evaluation (hr after challenge): 24hr and 48hr

OTHER:First induction exposure on Day 0: intradermal injections of FCA (to enhance a possible sensitisation)

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

periodic check with hexylcinnamic aldehyde

Statistics:

No data avaliable

Positive control results:

80 % of the positive control animals were sensitized.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no skin sensitisation was observed in test group

Remarks on result:

no indication of skin sensitisation

Remarks:

Not sensitizing in guinea pig

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no skin sensitisation was observed in test group

Remarks on result:

no indication of skin sensitisation

Remarks:

no skin sensitisation was observed in test group

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 5 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 ( not "r") )  )  and "s" )  and "t" )  and ("u" and "v" )  )

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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain 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 >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 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, 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 >> 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 by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters 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: "j"

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: "k"

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

Domain logical expression index: "l"

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: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) OR Nonionic Surfactants OR Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "s"

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: "t"

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

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.32

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.156

Interpretation of results:

other: Not sensitizing

Conclusions:

The skin sensitization potential of 2-bromoethanaminium bromide (2576-47-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances 2-bromoethanaminium bromide (2576-47-8) was predicted to be not sensitizing to the skin of Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 2-bromoethanaminium bromide(2576-47-8) estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances 2-bromoethanaminium bromide(2576-47-8) was predicted to be not sensitizing to the skin of Dunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 2-bromoethanaminium bromide (2576-47-8) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guineapig for target chemical 2-bromoethanaminium bromide (2576-47-8) and its structurally similar read across substances11-aminoundecanoic acid(2432-99-7)andGlutamic acid (56-86-0). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across.

The skin sensitization potential of 2-bromoethanaminium bromide(2576-47-8) estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances 2-bromoethanaminium bromide(2576-47-8) was predicted to be not sensitizing to the skin of Dunkin-Hartley guinea pig.

Supported by experimental data conducted by OECD SIDS-SIAM 15 (SIDS Initial Assessment Report for SIAM 15, 2002.) on structurally similar read across substance11-aminoundecanoic acid (2432-99-7)in guinea pig.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Group of 30 animals were observed for sensitization test. During the induction period, the reference substance DNCB was applied at the concentrations of 0.1 % (w/w) (day 1) and I % (w/w) (day 8) in corn oil. For the challenge application, the reference substance DNCB was applied at the concentration of 1% (w/w) in corn oil. On day 22, after a rest period of 12 days, all animals of the treated and control groups were challenged by a cutaneous application of the test Substance in concentration 40% w/w in corn oil to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing. No skin sensitization was observed after the challenge application and no deaths were noted during the study. Hence11-aminoundecanoic acid was considered as not skin sensitizing in guinea pig.

It is further supported by an experimental study conducted  by European Chemical Agency (ECHA) (OECD HPV Chemical Programme, SIDS Dossier,2013)on structurally similar read across substance Glutamic acid (56-86-0) on guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance.

Thus based on the above predictions on 2-bromoethanaminium bromide (2576-47-8) as well as its read across substances and applying weight of evidence, it can be concluded that 2-bromoethanaminium bromide (2576-47-8) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2-bromoethanaminium bromide (2576-47-8) can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, 2-bromoethanaminium bromide (2576-47-8) can be considered as not classified for skin sensitization effects