3-methyl-1-phenylpyrazol-5-ylamine

Endpoint summary

Description of key information

Acute toxicity: oral

The acute oral median lethal dose (LD50) of 3-methyl-1-phenylpyrazol-5-ylamine, when administered to rat was found to be 2500 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimation

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: 5-Amino-3-methyl-1-phenyl-pyrazol
- IUPAC name: 3-methyl-1-phenylpyrazol-5-ylamine
- Molecular Formula: C10H11N3
- Molecular weight: 173.2179 g/mole
- Substance type: Organic

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

No data available

Doses:

2012 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 012 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data available

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 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 ( not "m") )  )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

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 - alkenyl pyridines, pyrazines, pyrimidines or triazines  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic Amines OR Benzotriazoles (Acute toxicity) OR Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as > 100 days OR 1 to 10 days OR 10 to 100 days by Ultimate biodeg

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor AND Hydrazine AND Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Heterocyclic Polycyclic Aromatic Hydrocarbons OR No alert found OR Polycyclic Aromatic Hydrocarbons by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.959

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.64

Interpretation of results:

other: not classified

Conclusions:

LD50 was estimated to be 2844 mg/kg bw for Wistar male and female rats.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3-methyl-1-phenyl-1H-pyrazol-5-amine. The LD50 was estimated to be 2844 mg/kg bw for Wistar male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Data is K4 level as the data has been obtained from the study report of ' LONZA Ltd.'

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

In different studies, 3-methyl-1-phenyl-1H-pyrazol-5-amine has been reviewed for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in mice and rats for 3-methyl-1-phenyl-1H-pyrazol-5-amine. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3-methyl-1-phenyl-1H-pyrazol-5-amine. The LD50 was estimated to be 2844 mg/kg bw for Wistar male and female rats.

In another study given by RTECS (Registry of Toxic Effects of Chemical Substances, 2012), rat were treated with 3-methyl-1-phenyl-1H-pyrazol-5-amine in the concentration of 2500 mg/kg bw orally. 50 % mortality was observed in treated rats at 2500 mg/kg bw. Changes in motor activity were observed. Therefore, LD50 was considered to be 2500 mg/kg bw when rat were treated with 3-methyl-1-phenyl-1H-pyrazol-5-amine orally.

Thus, based on the above studies and predictions on 3-methyl-1-phenyl-1H-pyrazol-5-amine, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3-methyl-1-phenyl-1H-pyrazol-5-amine can be Not classified as acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 3-methyl-1-phenyl-1H-pyrazol-5-amine, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3-methyl-1-phenyl-1H-pyrazol-5-amine can be not classified as acute oral toxicity.