Fatty acids, C5-9, hexaesters with dipentaerythritol

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no information on purity of the test material; both flanks were exposed during challenge, no reliability check done, no positive control used. Method given in very summarized form).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

no information on purity of the test material; both flanks were exposed during challenge, no reliability check done, no positive control used. Method given in very summarized form.

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

The test was performed in 1991 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods".

Species:

guinea pig

Strain:

other: Albino

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 344 - 441 g

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

Induction: 100%
Challenge: 30% and 100%

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

Induction: 100%
Challenge: 30% and 100%

No. of animals per dose:

20 (10 for the controls)

Details on study design:

RANGE FINDING TESTS: No Data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: Undiluted test sample
- Control group: not stated
- Site: scapular region
- Frequency of applications: 7 d interval
- Duration: 14 d
- Concentrations: undiluted

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28, 14 d after final induction
- Exposure period: 6 h
- Test groups: undiluted (100%) and 30% (w/v in corn oil)
- Control group: undiluted (100%) and 30% (w/v in corn oil)
- Site: undiluted (100%) on left flank and 30% on right flank
- Concentrations: undiluted (100%) and 30% (w/v in corn oil)
- Evaluation (hr after challenge): 24 h and 48 h

Challenge controls:

No

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0.

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

There are no data available for on the skin sensitisation potential of the substance Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 677262-52-1). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was 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 toxicological properties may be predicted from data for the reference substance(s) on the basis of structural similarity, the substances listed below are selected as reference substances for assessment of toxicological endpoints, for which information gaps are identified.

 

Overview of skin sensitisation

CAS	Skin Sentisation
67762-52-1(a)	RA: CAS 68424-31-7
68424-31-7(b)	Not Sensitizing

(a) Substances subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural and similar properties and/or activities. The available endpoint information is used to predict Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 677262-52-1).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Since no studies investigating the sensitisation of Fatty acids, C5-9, hexaesters with dipentaerythritol (CAS# 67762-52-1) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was conducted.

 

CAS 68424-31-7

Four studies were conducted with fatty Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) according to OECD Guideline 406 (Buehler Test) and OECD Guideline 429 (Local Lymph Node Assay).

The skin sensitisation potential of Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7) was evaluated in guinea pigs with a Buehler test for skin sensitization (Lees, 1991a). 20 male albino guinea pigs were treated with the test substance and compared with 10 control animals. Three epidermal inductions were performed with 100 % test substance in weekly intervals for 6 hours under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 hours epicutaneously with 100% (left shorn flank) and 30% (right shorn flank) test substance (diluted in corn oil) under occlusive conditions. Animals were evaluated for skin reactions 24 and 48 h after challenge. No signs for irritation or sensitisation were observed during induction and challenge of the animals.

 

This result is supported by the results of a Local Lymph Node Assay which was reported only as a short summary (Bugg, 1992). No details on the study protocol or the data interpretation was given., neverthelessNevertheless, the data presented (concentrations of the test sample were 1%, 3%, and 10%, CPM/lymph node and the test/control ratio, accordance to GLP) indicate that the test substance was not a sensitizer under the conditions tested.

 

Furthermore, another Local Lymph Node Assay was conducted (Robinson, 1991b). The test substance was applied in concentrations of 3%, 10% and 30% on three consecutive days to the dorsum of both ears of 4 female CBA/Ca mice each. Five days later the animals received approx. 20 µCi of 3H-methlyl thymidine and were sacrificed 5 h later for measurement of radioactivity. No significant increase in isotope incorporation was detected after repeated application. The stimulation index, calculated by comparison of the Cpm of the control and the treated animals, was 0.45 for the 3% application, 2.05 for 10% and 1.21 for the 30% application. According to the provider, the test substance contained up to 2% of an additional package which was not further defined. This might contribute to the result of this test. Therefore the result cannot be clearly assigned to the test substance and this study is not considered for classification.

In a fourth study, a Local Lymph Node Assay, was conducted analogously to the one reported previously but with significant methodical deficiencies (Robinson, 1991c). Only low (3%) and medium (10%) concentrations of the test substance (again containing the additives which were not further specified) were applied instead of the three as demanded by the regulatory authorities. Therefore the results obtained do not allow the derivation of a dose dependency and are insufficient for assessment.

 

Based on the study results no classification is required according to EU classification criteria for skin sensitisation.

Conclusion for skin sensitization

1 Buehler assay has been conducted withthe structural related read-across analogue substances Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7). There is no evidence for a skin sensitizing potential in this assay. Additionally, 3 LLNAs are available all conducted with Fatty acids, C5-10, esters with pentaerythritol (CAS# 68424-31-7), of which only one is suitable for assessment and shows a negative result as well.Therefore, based on a structural related read-across approach,in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, fatty acids C5-10 esters with dipentaerythritol (CAS# 67762-52-1)is not considered to have skin sensitizing potential.

Migrated from Short description of key information:
Skin sensitisation: not sensitising (OECD 406, analogue approach)

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The available studys is adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Based on read-across from 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.