Benzoic acid, 4-hydroxy-, C18-22-alkyl esters

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

yes

Remarks:

(study report with limited information; rechallenge was conducted sytemically)

GLP compliance:

no

Type of study:

Buehler test

Justification for non-LLNA method:

A valid Buehler test was available before REACh came into force, therefore no additional LLNA test was performed.

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 260-352 g
No further information is given in the study report.

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

10% (w/w) in aqueous suspension

Route:

other: topical and systemic (not further specified)

Vehicle:

water

Concentration / amount:

10% (w/w) in aqueous suspension

No. of animals per dose:

12

Details on study design:

RANGE FINDING TESTS:
No information provided in the study report.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 6 h
- Test groups: test substance
- Control group: no data
- Site: no data
- Frequency of applications: not specified
- Duration: Days 0-21 days
- Concentrations: 10% (w/w) aqueous suspensio)

B. CHALLENGE EXPOSURE
- No. of exposures: 2 (topical and systemic)
- Day(s) of challenge: 14 days after induction (not further specified)
- Exposure period: no data
- Test groups: test substance
- Control group: no data
- Site: no data
- Concentrations: 10% (w/w) aqueous suspensio)
- Evaluation (hr after challenge): no data

Reading:

other: after topical challenge

Group:

test chemical

Dose level:

10% aqueous suspension

No. with + reactions:

0

Total no. in group:

12

Remarks on result:

other: Reading: other: after topical challenge. Group: test group. Dose level: 10% aqueous suspension. No with. + reactions: 0.0. Total no. in groups: 12.0.

Reading:

other: after systemic challenge

Group:

test chemical

Dose level:

10 % aqueous suspension

No. with + reactions:

0

Total no. in group:

12

Remarks on result:

other: Reading: other: after systemic challenge. Group: test group. Dose level: 10 % aqueous suspension. No with. + reactions: 0.0. Total no. in groups: 12.0.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Justification for grouping of substances and read-across

No data are available on the skin sensitisation potential of Benzoic acid, 4-hydroxy-, C18-22-alkyl esters (CAS 201305-16-0). In order to fulfil the standard information requirements set out in Annex VII in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, the substances depicted in the table below are selected as source substances for assessment.

The read-across is based on the identified structural similarities and the likelihood of common breakdown products by biological processes (metabolism). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

CAS	201305-16-0	68411-27-8	94-13-3
Chemical Name	Benzoic acid, 4-hydroxy-, C18-22-alkyl esters	Benzoic acid,C12-15-alkyl esters	Propyl 4-hydroxybenzoate
MW	390.60-446.71 g/mol	311 g/mol	180.2 g/mol
Skin sensitisation	RA: CAS 68411-27-8, CAS 94-26-8	Experimental result: Not sensitising (OECD 406) Not sensitising (RIPT)	Experimental result: Not sensitising (secondary source information)

 

Skin sensitisation

CAS 68411-27-8

A Buehler test is available which was conducted similar to OECD guideline 406, where twelve male guinea pigs, weighing 260-352 g were tested. The animals were treated with 9 topical, occluded applications (duration of treatment 6 hours/day) over a 21 day period. Two challenge applications were performed 14 days later, to determine local and systemic effects. Non-irritating concentrations (10 % (w/w)) were used. No positive reactions were observed, neither after topical challenge, nor after systemic challenge. Therefore the authors of the study report concluded that the test material was not a potential sensitizer in guinea pigs under the experimental conditions chosen.

A Repeated Insult Patch Test (RIPT) was conducted in humans, based on the Draize - Shelanski Test Method. A panel of minimum 200 volunteers was tested for primary or cumulative irritation and/or sensitisation after repeated dermal contact with the test item. The test material was applied at a concentration of 10 % (w/w) in mineral oil.The volar forearm or upper back between the scapulae served as the treatment area. Approximately 0.15 mL of the test material was applied to the gauze portion of a Coverlet adhesive dressing. This was then applied to the treatment site to form an occlusive patch. This procedure was followed three times per week for a total of ten applications. Each site was marked to ensure the continuity of patch application. The participants were instructed to remove these patches after 24 hours. The evaluation of each site was made just prior to re-application. Rest periods consisted of 24 hours following the Tuesday and Thursday removal, and 48 hours following the Saturday removal.At the conclusion of a fourteen day rest period following the –tenth application, a challenge patch was applied to the original site and to a virgin site following the previously described procedure. Each site was then evaluated at 24 and 48 hours after application.No positive reactions were observed, neither for irritation, nor for sensitisation. Thus, the test item is not sensitising or irritating to humans after repeated dermal application of 10% solution in mineral oil.

CAS 94-13-3

In a maximization test with a multiple dosedesign in guinea pigs, Andersen et al. (1995) did not find any significant sensitization potential withPropyl 4-hydroxybenzoate.The concentration ranges used for induction and challenge in the multiple dose GPMT were based on a preliminary pilot study using FCS-treated naive guinea pigs. 5 female albino guinea pigs per test group, weighing between 350 and 450 g at receipt were treated according to the procedure described by Magnussen and Kligman, comprising an intracutaneous induction (0.1, 0.3, 1, 3 and 10%)with FCA on day 0, a topical induction on day 7 (0.3 and 30%)and a subsequent challenge (10%)on day 21 by closed patch tests to the flank of the animal. No pretreatment of the topical induction area with sodium lauryl sulphate was performed. The challenge reactions were blindly read after 48 h and 72 h. No positive reactions were observed for sensitisation. The test item was not sensitising in the GPMT under the experimental conditions chosen. Considering the results of all induction groups, the concurrently tested substances formaldehyde, mercaptobenzothiazole and chlormethylisothiazolinone/ methylisothiazolinone induced each positive reactions in at least 13/25 and up to 24/25 animals (52-96%), thus meeting the reliability criteria for the GPMT (≥ 30% positive response).

Additional experimental data on skin sensitisation for Propyl 4-hydroxybenzoate is available as secondary source only, and reviews. No details on the study designs or raw data are given.In a murine local lymph node assay (LLNA), Basketter et al. (2001) studied several chemicals that can act as contact allergens. In this study,Propyl 4-hydroxybenzoatewas reported as non-sensitizing. In another study, Basketter et al. (1999) determined the threshold of 134 chemicals, includingPropyl 4-hydroxybenzoate, for classification as skin sensitizer.Propyl 4-hydroxybenzoatewas reported negative in the LLNA assay and the guinea pig maximization test (GMPT).

Migrated from Short description of key information:
Skin: not sensitising

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues/surrogates. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substances and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read-across from the structurally similar substances, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available for respiratory sensitisation.