N,N-dimethylglycinium chloride

Endpoint summary

Description of key information

The skin sensitization potential of 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material : 2-(dimethylamino)acetic acid hydrochloride; N,N-dimethylglycinium chloride
- Molecular formula : C4H10ClNO2
- Molecular weight : 139.581 g/mol
- Smiles notation : OC(=O)CN(C)C.Cl
- InChl : 1S/C4H9NO2.ClH/c1-5(2)3-4(6)7;/h3H2,1-2H3,(H,6,7);1H
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary OR Carboxylic acid OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary OR Carboxylic acid OR No functional group found OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Amino, aliphatic attach [-N<] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic acid derivative OR No functional group found OR Tertiary aliphatic amine OR Tertiary amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD ONLY

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 Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, NH2 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 OASIS v1.3 ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Amino, aliphatic attach [-N<] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND No functional group found AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "n"

Similarity boundary:Target: Cl_CN(C)CC(O)=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Cl_CN(C)CC(O)=O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Cl_CN(C)CC(O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Carboxylic acids (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "s"

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: "t"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= -6.2

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.236

Interpretation of results:

other: Not sensitizing

Conclusions:

 The substance 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) and its structurally similar read across substancesAdipic acid (CAS no: 124-04-9)andGlycine (CAS no: 56-40-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

The Cosmetic Ingredient Review Expert Panel {International Journal of Toxicology; 2012 Jul-Aug;31(4 Suppl):5S-76S} conductedskin sensitization study for read across substanceAdipic acid (CAS no: 124-04-9) in group of ten guinea pigs that supports the above mentioned result. For induction, 0.1ml of 1% aqueous solution of adipic cid was given as a sacral intradermal injection, once a week for 4 weeks. After a rest period of 2 weeks, animals were challenged with 0.05ml of 5% of adipic acid in propylene glycol. None of the treated guinea pig induced skin sensitization reaction. Hence the chemical Adipic acid (CAS no: 124-04-9)was considered to be not sensitizing to the skin of guinea pigs.

 

The above results were further supported by the Human Repeated Insult Patch Test of read across chemical Glycine (CAS no: 56-40-6) conducted in 104 patients under occlusive condition by Cosmetic Ingredient Review Expert Panel {International Journal of Toxicology; 2013 Nov-Dec;32(6 Suppl):41S-64S}. When the chemical was tested at a dose of 2% in moisturizer under occlusive condition, no skin sensitization effects were observed. Hence the chemical Glycine (CAS no: 56-40-6)was considered to the skin of 104 patients in aHuman Repeated Insult Patch Test.

 

Thus on the basis of available data for thetarget chemical2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) and its structurally similar read across substancesAdipic acid (CAS no: 124-04-9)andGlycine (CAS no: 56-40-6),it can be concluded thatchemical 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) is unable to cause skin sensitization and considered as non-skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) and its structurally similar read across substancesAdipic acid (CAS no: 124-04-9)andGlycine (CAS no: 56-40-6) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-(dimethylamino)acetic acid hydrochloride (CAS NO: 2491-06-7) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.