3-methyl-1-phenylpyrazol-5-ylamine

Endpoint summary

Description of key information

The skin sensitization potential of 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6)was predicted to be non sensitizing to the skin of male Dunkin-Hartley guinea pig.

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 v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3.

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 :3-methyl-1-phenyl-1H-pyrazol-5-amine
- Molecular formula: C10H11N3
- Molecular weight : 173.2179 g/mol
- Smiles notation : Cc1cc(n(n1)c2ccccc2)N
- InChl:1S/C10H11N3/c1-8-7-10(11)13(12-8)9-5-3-2-4-6-9/h2-7H,11H2,1H3
- Substance type:Organic
- Physical state:Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

No data available.

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Route:

epicutaneous, semiocclusive

Vehicle:

propylene glycol

Day(s)/duration:

24hour

No. of animals per dose:

20 Test group

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Statistics:

No data available.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization effect were observed.

Remarks on result:

no indication of skin sensitisation

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Aryl OR Pyrazole by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Aryl OR Overlapping groups OR Pyrazole by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as 1,1-Diaminoalkene derivative [C=C(N)N]  OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Aromatic Nitrogen, five-member ring OR Azomethine, aliphatic attach [-N=C] OR Hydrazine [>N-N<] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound OR CO2 derivative (general) OR Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

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: "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 >> Vinyl pyridines by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

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: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

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 Group 14 - Carbon C AND Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 4 - Trans.Metals Ti,Zr,Hf by Chemical elements

Domain logical expression index: "o"

Similarity boundary:Target: CC1C=C(N)N(c2ccccc2)N=1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.263

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.78

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6)was predicted to be non sensitizing to the skin of male Dunkin-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6)was predicted to be non sensitizing to the skin of male Dunkin-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) has been investigated for potential dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea pig for target chemical 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) and its structurally similar read across substancesSodium dodecylbenzenesulfonate (25155-30-0) and sodium 2-methylprop-2-ene-1-sulfonate(CAS No:-1561-92-8). The predicted data using the OECD QSAR toolbox and DANISH QSAR have also been compared with the experimental data.

The skin sensitization potential of 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6)was predicted to be non sensitizing to the skin of maleDunkin-Hartley guinea pig.

 Supportedby an experimental study conducted  by U.S. Environmental Protection Agency (U.S. Environmental Protection Agency Risk-Based Prioritization Document, 2009,)on structurally similar read across substance 1, 3-Diphenylguanidine( 102-06-7)on guinea pigs.The skin sensitization study of 1, 3-Diphenylguanidine (102 -06 -7) was performed in 15 guinea pigs by using Guinea pig maximization test. In induction phase, on 1stday intradermal injection of 0.1ml of 1.0%w/w1, 3-Diphenylguanidine in paraffin oil in presence of Freund’s complete adjuvant was given .on day 8, occlusive dressing of0.5 ml of 25%w/w1, 3-Diphenylguanidine in paraffin oil was applied for 48hr.In challenge phase, after 12 days 0.5 ml of 25%w/w1, 3-Diphenylguanidine in paraffin oil was applied for 24hr, as occlusive patch. The evolution done 24hr and 48hr after removal of challenge application. No sensitization reaction was observed at application site .Hence it is considered that 1, 3-Diphenylguanidine (102 -06 -7) was not skin sensitizing in guinea pig.

It is further Supported by experimental data conducted by Majka K (UNEP)( Med P ,1979) )on structurally similar read across substance Nicotinonitrile (100-54-9) in rabbit . 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. Skin sensitizing test was conducted for Pyridine-3-carbonitrile in rabbit. Allergic effect was not observed. Therefore Nicotinonitrile (100-54-9) was considered to be non sensitizing to rabbit skin.

Thus based on the above predictions on 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6)  as well as its read across substances and applying weight of evidence, it can be concluded that 3-methyl-1-phenylpyrazol-5-ylamine is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) 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, 3-methyl-1-phenylpyrazol-5-ylamine (1131-18-6) can be considered as not classified for skin sensitization effects.