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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation, other
Remarks:
in silico
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 adequate and reliable documentation / justification
Remarks:
QSAR toolbox
Justification for type of information:
1. SOFTWARE
QSAR Toolbox 3.3.0.152, Databse version: 3.8.3/3.1.2.

2. MODEL (incl. version number)
Human Health, Skin Sensitisation II (ECETOC)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Target chemical: CAS no. 80-70-6, 1.1.3.3.-tetramethylguanidine, SMILES: CN(C)C(=N)N(C)C
Source chemicals:
- CAS no. 15894-70-9, guanidine, n,n’’’-1,6-hexanediylbis[n’-cyano, SMILES: N=C(NCCCCCCNC(=N)NC#N)NC#N
- CAS no. 461-58-5, 2-cyanoguanidine, SMILES: NC(N)=NC#N
- CAS no. 102-06-7, 1,3-diphenylguanidine, SMILES: NC(Nc1ccccc1)=Nc1ccccc1
- CAS no. 97-39-2, guanidine, n,n'-bis(2-methylphenyl)-, SMILES: Cc1ccccc1NC(=N)Nc1ccccc1C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Human Health Hazards, Sensitisation: Skin Sensitisation II (ECETOC) - SWAN; Skin sensitisation in vivo, Guinea pig (OECD Principle 1)
- Unambiguous algorithm: Read-across from category members. Takes highest mode value from the 5 nearest neighbours. (OECD Principle 2) --> predicted value: Negative.
- Defined domain of applicability: The target chemical FALLS within applicability domain (OECD Principle 3).
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 5 neighbours' values, 5 of them equal to prediction: "Negative". Prediction confidence is measured by the p-value = 0.0312 (moderate confidence) (OECD Principle 4)
- Mechanistic interpretation: Chemical and biological mechanisms (OECD Principle 5): DNA binding by OECD, Estrogen Receptor Binding, OECD HPV Chemical Categories, Protein binding by OECD, Protein binding potency, Superfragments, Toxic hazard classification by Cramer (original), US-EPA New Chemical Categories.

5. APPLICABILITY DOMAIN
The target chemical should be classified as Guanidine by Organic Functional groups (nested)
The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N by Chemical elements
The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements
The target chemical should have a value of log Kow which is >= -1.34
The target chemical should have a value of log Kow which is <= 2.89

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
no guideline available
Version / remarks:
The template of the report is based on "GUIDANCE DOCUMENT ON THE VALIDATION OF (QUANTITATIVE) STRUCTURE-ACTIVITY RELATIONSHIPS MODELS" published by OECD (September, 2007) and "GUIDANCE ON INFORMATION REQUIREMENTS AND CHEMICAL SAFETY ASSESSMENT / CHAPTER R.6: QSARS AND GROUPING OF CHEMICALS" published by ECHA (May, 2008).
Principles of method if other than guideline:
see field 'Justification for type of information'
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,3,3-tetramethylguanidine
EC Number:
201-302-7
EC Name:
1,1,3,3-tetramethylguanidine
Cas Number:
80-70-6
Molecular formula:
C5H13N3
IUPAC Name:
N,N,N',N'-tetramethylguanidine

Results and discussion

In vivo (LLNA)

Results
Parameter:
other: predicted skin sensitisation
Remarks on result:
no indication of skin sensitisation based on QSAR/QSPR prediction

Any other information on results incl. tables

Prediction of S W A N; Skin Sensitisation for 1,1,3,3-tetramethylguanidine

Toxicity of the target chemical (Negative) is predicted from category members using read-across based on 5 values (Negative x5) from 5 nearest neighbours compared by prediction descriptors. Category members are single chemicals or mixtures and are selected based on the profile of the target chemical. Only chemicals having experimental data are listed in the category.

The target chemical FALLS within applicability domain of the prediction ( see field 'Justification for type of information').

The data used for calculating the current prediction is taken from 9 experimental values selected from the following database(s): 1. ECHA CHEM, 2. Skin Sensitization

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met