3'-nitroacetophenone

Endpoint summary

Description of key information

The skin sensitization potential of 3'-nitroacetophenone (121-89-1) 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'-nitroacetophenone (121-89-1) was predicted to be non sensitizing to the skin of male and female-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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: Prediction was done using OECD QSAR toolbox v3.3

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Remarks:

data submitter is the owner of the prediction report

Type of study:

Draize test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

Name of test material (as cited in study report): 3 nitro acetophenone
Molecular formula : C8H7NO3
Molecular weight: 165.147 g/mol
Smiles notation : c1(cc(ccc1)[N+](=O)[O])C(C)=O
InChl : 1S/C8H7NO3/c16(10)73248(57)9(11)12/h25H,1H3
Substance type: Organic
Physical state: Solid

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 350 g
- Housing: wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): pelleted guinea pig diet, cabbage, hay.
- Water (e.g. ad libitum): water ad libitum

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data

Day(s)/duration:

No data

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

Intradermal injection challenge concentration (ICC): 0.25 %
Topical application challenge concentration (ACC): 20 %

No. of animals per dose:

10 animals
Either 4 males and 6 females or visa versa

Details on study design:

Details on study design
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: 14 days
- Test groups: 1
- Control group: no data
- Site: intradermally and topically on the shaved flanks
- Frequency of applications: 2.5 times
- Duration: 24 hrs
- Concentrations: 0.1 ml

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 7 days
- Exposure period: 21 days
- Test groups:1
- Control group: no data
- Site: 4 sites (2 auxillary and 2
inguinal lymph nodes.)
- Concentrations: 0.1 ml
- Evaluation (hr after challenge): 24 hrs

OTHER: RECHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: 14 days
- Exposure period: 35 days
- Test groups: 1
- Control group: no data
- Site: 4 sites (2 auxillary and 2
inguinal lymph nodes.)
- Concentrations: 0.1 ml
- Evaluation (hr after challenge): 24 hrs

Challenge controls:

Yes

Positive control substance(s):

not specified

Statistics:

No data available

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No sensitization reaction 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 highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" or "d" or "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 ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Ketone AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Ketone AND Nitrobenzene AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitro, aromatic attach [-NO2] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonyl compound AND Ketone AND Nitro compound by Organic functional groups, Norbert Haider (checkmol)

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones 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 by ROS formation OR Radical >> Radical mechanism by ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives 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) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH 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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates  OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitro, aromatic attach [-NO2] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Acyclic carbonyl, two aromatic attach OR Carbonyl, non-cyclic, two aromatic attach [-C(=O)-] OR Cyano, aliphatic attach [-C#N] OR Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.627

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.07

Interpretation of results:

other: Negative

Conclusions:

The skin sensitization potential of 3'-nitroacetophenone (121-89-1) 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'-nitroacetophenone (121-89-1) was predicted to be non sensitizing to the skin of male and female-Hartley guinea pig.

Executive summary:

The skin sensitization potential of 3'-nitroacetophenone (121-89-1) 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'-nitroacetophenone (121-89-1) was predicted to be non sensitizing to the skin of male and female-Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 3'-nitroacetophenone (121-89-1) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea for target chemical 3'-nitroacetophenone (121-89-1) and its structurally similar read across substances Acetophenone (98 -86-2) and 4-phenylbutan-2-one (2550-26-7). The predicted data using the OECD QSAR toolbox and DANISH QSAR have also been compared with the experimental data of read across.

The skin sensitization potential of 3'-nitroacetophenone (121-89-1) 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'-nitroacetophenone (121-89-1) was predicted to be non sensitizing to the skin of male and female-Hartley guinea pig.

In other prediction done by Danish QSAR (2017) , to evaluate the skin sensitization potentialof 3'-nitroacetophenone (121-89-1) .Using Battery algorithm model of Danish QSAR,Allergic Contact Dermatitis for 3'-nitroacetophenone estimated to be not sensitizing when applied to human and guinea pig skin.

This is further supported by experimental data conducted by D.W. SHARP (Toxicology,1978) )on structurally similar read across substance Acetophenone (98 -86-2) on male and female Hartley 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. Acetophenone (98 -86-2) was tested in modified Draize test with groups of 10 male and female Hartley guinea pigs. For induction treatment, 0.1 ml aliquots of the test substance at 2.5 times the injection challenge concentration (ICC) were administered on one occasion as 4 intradermal injections at 4 sites which overlied the 2 auxilary and 2 inguinal lymph nodes. After an induction time of 14 days, the challenge treatment consisted of an intradermal injection in one flank and topical application (uncovered) on the other flank with an application challenge concentration (ACC) of 20 %. Reactions were scored 24 hrs later. In the absence of sensitization reactions at first challenge, the induction and challenge procedures were repeated, but this time a confirmatory challenge with controls was included. At each challenge 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC, respectively.No sensitization reaction were observed,Acetophenone (98 -86-2) was assessed as non-sensitizing.

It is further supported by Opdyke, D. L. J.; Letizia, C.( Food and Chemical Toxicology ,1983)on structurally similar read across substance 4-phenylbutan-2-one (2550-26-7)on human.A maximization test was carried out on 35 human volunteers. The 4-phenylbutan-2-onewas tested at a concentration of 2% in petrolatum in 35 humans. 4-phenylbutan-2-one produced no sensitization reactions. Therefore 4-phenylbutan-2-one was considered to be non sensitizing in human .

Thus based on the above predictions on 3'-nitroacetophenone (121-89-1) as well as its read across substances and applying weight of evidence, it can be concluded that 3'-nitroacetophenoneis not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3'-nitroacetophenone (121-89-1) 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'-nitroacetophenone (121-89-1) can be considered as not classified for skin sensitization effects.