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

Endpoint summary

Description of key information

Skin: not irritating
Eye: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

(study report with limited information)

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.8-2.4 kg
No further details are given in the study report.

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye remained untreated and served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): neat

Duration of treatment / exposure:

Single administration without washing

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 (mixed sex)

Details on study design:

SCORING SYSTEM: Draize Scoring System

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over all 6 animals

Time point:

other: mean over 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

over all 6 animals

Time point:

other: mean over 24, 48, and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

over all 6 animals

Time point:

other: mean over 24, 48, and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over all 6 animals

Time point:

other: mean over 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Interpretation of results:

not irritating

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 irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

No data are available on the acute toxicity 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 VIII 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 TARGET SUBSTANCE	68411-27-8
Chemical Name	Benzoic acid, 4-hydroxy-, C18-22-alkyl esters	Benzoic acid,C12-15-alkyl esters
MW	390.60-446.71 g/mol	311 g/mol
Skin irritation	RA WoE: CAS 16958-92-2, 99-76-3, 120-47-8, 94-13-3, 94-26-8	Experimental result: LD50 (rat) = 34500 mg/kg bw
Eye irritation	RA: CAS 68411-27-8	LC50 (rat) > 50 mg/L

 

Skin irritation

No data are available for the skin irritation potential of Benzoic acid, 4-hydroxy-, C18-22-alkyl esters (CAS 201305-16-0). To sufficiently cover this endpoint, data from the structurally related substance, i.e. Benzoic acid, C12-15-alkyl esters was used for read-across based on an analogue approach.

One study investigating the skin irritation potential of Benzoic acid,C12-15-alkyl esters was performed in vitro on human-derived epidermal keratinocytes (NHEK) similarly to OECD guideline 439 under GLP conditions (Nitka, 1999). NHEK were cultured to form a multilayered, highly differentiated model of the human epidermis (Epiderm TM). Subsequently, human reconstructed epidermis models were treated with 100 µL of the undiluted test substance for 1, 4.5 and 20 h. Each experiment was performed in triplicate. After the respective exposure periods cell viability was assessed using the MTT-Assay and expressed as percent of negative control. The viability of cells was 85, 80 and 78 % after 1, 4.5 and 20 h exposure period. Thus, the time at which a viability of 50% (ET-50) would be achieved was assumed to be greater than 24 h. The positive control (1% Triton X 100) revealed cell viabilities of 78, 37 and 5% after 1, 4.5 and 20 h exposure period and thus proved the validity of the result. Based on these data the test substance was not skin irritating in vitro.

A further study withBenzoic acid, C12-15-alkyl esters was performed on abraded and non-abraded skin of 6 rabbits under occlusive conditions (Brown, 1978). No guideline was followed but the study was conducted prior the establishment of current testing guidelines. Animals were treated with 0.5 mL of test substance for 24 h under occlusive conditions. Scoring was done after 24 and 72 h according to Draize and a primary dermal irritation index (PDII) was reported. The mean PDII of all 6 animals was 0.08 of maximum 8. No individual scores were reported and consequently the data cannot be directly compared to the requirements resulting in classification/non-classification. However, the test item was tested on abraded and non-abraded skin under occlusive conditions. Testing on abraded skin and the usage of occlusive conditions represents a reasonable worst case scenario. Even under this sound conditions a primary dermal irritation score of 0.08 (max achievable score = 8) was calculated. Thus, the test item is concluded to be not irritating to skin.

Eye irritation

The eye irritation potential of Benzoic acid, C12-15-alkyl esters was assessed in a study performed similarly to OECD Guideline 405 with rabbits. 0.1 mL of the undiluted substance was instilled into one eye of each of six rabbits. No washing was performed and the untreated eye served as control. Scoring was done 24, 48 and 72 h after instillation. No effects on cornea, iris and conjunctiva (neither chemosis nor redness) were observed. Thus the substance was not irritating to the eye.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue and based on the weight of evidence from all available studies.

Justification for selection of eye irritation 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).

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.