3'-hydroxyacetophenone

Endpoint summary

Description of key information

OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical 3'-Hydroxyacetophenone (CAS No: 121-71-1) by Buehler test on Hartley guinea pigs. According to this prediction model, the test chemical failed to induce skin sensitization in guinea pigs. Thus the test compound 3'-Hydroxyacetophenone (CAS No: 121-71-1) is estimated to be non-sensitizing to skin of Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from Prediction is done using QSAR Toolbox version 3.4

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4.

GLP compliance:

not specified

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

no data

Route:

epicutaneous, occlusive

Vehicle:

propylene glycol

Concentration / amount:

no data

Route:

epicutaneous, occlusive

Vehicle:

propylene glycol

Concentration / amount:

no data

No. of animals per dose:

5 male, 5 female

Details on study design:

no data

Challenge controls:

no data

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

28

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

not sensitising

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 28.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: not sensitising.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 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 ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND 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 Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] 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 Hydroxy compound AND Ketone AND Phenol 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.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0559

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.12

Interpretation of results:

not sensitising

Conclusions:

The substance 3'-Hydroxyacetophenone is estimated to be not sensitising to skin of Hartley guinea pigs.

Executive summary:

The skin sensitization potential for 3'-Hydroxyacetophenone is estimated using OECD QSAR toolbox version 3.4

The test substance 3'-Hydroxyacetophenone is estimated to be not sensitising to skin of Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

Skin sensitization behaviour of test compound3'-Hydroxyacetophenone(CAS No: 121-71-1)have been summarized below by using data from prediction model based estimation and its read across substances.

OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical3'-Hydroxyacetophenone(CAS No: 121-71-1) by Buehler test on Hartley guinea pigs. According to this prediction model, the test chemical failed to induce skin sensitization in guinea pigs. Thus the test compound3'-Hydroxyacetophenone(CAS No: 121-71-1) is estimated to be non-sensitizing to skin of Hartley guinea pigs.

Skin sensitization effects were reported by MAK Value Documentation, 1991 for similar read across substance p-Chloro-m-cresol (PCMC) (CAS No: 59-50-7)on 671 patients with eczema in 6 Danish out-patient clinics to assess its skin sensitization potential. In this testthe patients (men) were treated with 1% of PCMC and observed for skin reactions.In spite of the fact that the selected patient collective included cases with severe irritation and skin lesions, no positive reactions were observed. Hence the test substancep-Chloro-m-cresol (PCMC) (CAS No: 59-50-7)was considered to be non-sensitizing on humans.

Another skin sensitization study was carried out byMAK Value Documentation, 1991on albino guinea pigs (Pirbright White) using the open epicutaneous test (OET) of Klecak for same read across chemicalChlorocresol(CAS No: 59-50-7).The induction treatment consisted in once daily application of 0.1 ml of a 1%, 3%, 10% or 30% PCMC-Lutrol mixture (5 days/week for 4 weeks) to a skin area of 8 cm2 on the clipped left flank of groups of 7 animals (♀). With one exception in the 30 % group, no skin reactions developed during the induction period. 4 and 6 weeks after the start of the induction treatment provocation doses of 0.025 ml of 3%, 10%, 30% and 100% PCMC were applied to 4 clipped sites, about 2 cm2 in area, on the right flanks of the guinea pigs. The undiluted substance produced red spots on the pretreated skin areas in some animals after 24 and 48 hours; no skin reactions were observed with the dilutions up to 30% PCMC. The authors considered the skin redness caused by the undiluted substance to be primary irritation and not to be due to sensitization and concluded that with induction concentrations up to 30% and challenge concentrations up to 100% there is no sensitization of the guinea pig skin in the OET. Therefore the test chemicalChlorocresol(CAS No: 59-50-7) was considered as non- sensitizing to guinea pigs.

OECD SIDS in 1999 reportedMouse local lymph node assay (LLNA) in 4 female CBA/Ca mice to assess the skin sensitization potential of test chemical 4-Hydroxybenzoic acid (CAS No: 99-96-7).In this assay, 4 animals were inducted by daily topical application of 2.5 – 15.0 % for three consecutive days. Five days after the initiation of exposure, [3H] methyl thymidine was injected and the labelling in lymph node cells was measured. The ratio of labelling incorporation by tested lymph node cells to that recorded for control lymph node cells, (T/C) ratio was 0.6 – 1.5 (more than 3.0 is positive).Since the (T/C) ratio was less than 3, the test chemical 4-Hydroxybenzoic acid (CAS No: 99-96-7) was considered to be non-sensitizing in Mouse local lymph node assay (LLNA).

Thus the available data estimated by prediction model for target substance3'-Hydroxyacetophenone(CAS No: 121-71-1) as well as available data for read across substances Chlorocresol(CAS No: 59-50-7) and4-Hydroxybenzoic acid (CAS No: 99-96-7)and applying weight of evidence approach suggests that the test chemical substance3'-Hydroxyacetophenone(CAS No: 121-71-1)  is not likely to cause skin sensitization and thus can be classified as non-skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test chemical substance3'-Hydroxyacetophenone(CAS No: 121-71-1)and its read acrosssubstances Chlorocresol(CAS No: 59-50-7) and4-Hydroxybenzoic acid (CAS No: 99-96-7)were observed in various studies. From the results obtained from these studies it is concluded that the chemical substance3'-Hydroxyacetophenone(CAS No: 121-71-1) was unable to cause skin sensitization and hence can be classified as non-skin sensitizing.