Pentadecan-15-olide

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, K, rel. 1).
Eye irritation: not irritating (Read-across: OECD 405 / EU B.5, GLP, WoE, rel. 2).
Respiratory irritation: this information is not available.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1994-11-28 to 1994-12-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD test guideline No. 404 and in compliance with GLP.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: stock Mol:Russian from Mollegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved
- Age at study initiation: no data
- Weight at study initiation: 2.0 - 2.3 kg bw
- Housing: individually, in 62 x 52 cm PPO cages with perforated floor
- Diet (e.g. ad libitum): A pelleted complete rabbit diet "Altromin 2123" from Chr. Petersen, DK-4100 Ringsted, was available ad libitum. Analyses for major nutritive components and significant contaminants are performed regularly on the diet. Certificates of analysis are retained.
- Water (e.g. ad libitum): The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for possible contaminants are performed regularly. Certificates of analysis are retained.
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%):55 +/- 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: Ethanol 96% and diethyl phthalate (DEP) (1 : 1 (w/w))

Controls:

other: one of the 6 test site per animal was a vehicle control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of each test concentration
- Concentration (if solution): 100%, 20% (w/w), 10% (w/w), 5% (w/w), 1% (w/w).

VEHICLE
- Source of the lot/batch no.: Merck, Bie & Berntsen, Denmark

Duration of treatment / exposure:

4 hours

Observation period:

14 days. Readings at 1, 24, 48 and 72 hours; then on Day 7 and 14.

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: an area of 10 x 10 cm on the back (2.5 x 2.5 cm per gauze patch). The clipped area was divided into 6 test sites: 2 anterior located test sites, 2 centrally located test sites and 2 posterior located test sites.
- Type of wrap if used: semi-occlusive dressing: a 1 cm wide adhesive tape and fixed with Scanpor tape, 4.5 cm width, loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with soap and lukewarm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale (according to OECD 404)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

4 animals

Time point:

other: mean 24, 48 and 72 hours

Score:

1.58

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Concentration = 100 %

Irritation parameter:

edema score

Basis:

mean

Remarks:

4 animals

Time point:

other: mean 24, 48 and 72 hours

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Concentration = 100 %

Irritant / corrosive response data:

In general slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarly in general slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed.
On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

Other effects:

none

Table 7.3.1/1: Mean irritant/corrosive response data for the 4 animals at each observation time up to removal of animals from the test – Concentration = 100 %

 

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	1	0
24 h	1.75	0
48 h	1.5	0.25
72 h	1.5	0
Average 24h, 48h, 72h	1.58	0.08
Reversibility*)	c.	c.
Average time (day) for reversion	14 d	3 d

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Table 7.3.1/2: Mean irritant/corrosive response data for the 4 animals at each observation time up to removal of animals from the test – Concentration = 20 %

 

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	1	0
24 h	1.5	0
48 h	1.5	0.25
72 h	1.5	0
Average 24h, 48h, 72h	1.5	0.08
Reversibility*)	c.	c.
Average time (day) for reversion	14 d	3 d

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Table 7.3.1/3: Mean irritant/corrosive response data for the 4 animals at each observation time up to removal of animals from the test – Concentration = 10 %

 

 

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	0.5	0
24 h	1	0
48 h	0.75	0
72 h	1	0
Average 24h, 48h, 72h	0.92	0.0
Reversibility*)	c.	-
Average time (day) for reversion	14 d	-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Table 7.3.1/4: Mean irritant/corrosive response data for the 4 animals at each observation time up to removal of animals from the test – Concentration = 5 %

  

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	0.25	0
24 h	0.5	0
48 h	0.25	0
72 h	0.5	0
Average 24h, 48h, 72h	0.42	0.0
Reversibility*)	c.	-
Average time (day) for reversion	14 d	-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Table 7.3.1/5: Mean irritant/corrosive response data for the 4 animals at each observation time up to removal of animals from the test – Concentration = 1 %

  

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	0.5	0
24 h	0.75	0
48 h	0.75	0
72 h	0.5	0
Average 24h, 48h, 72h	0.67	0.0
Reversibility*)	c.	-
Average time (day) for reversion	14 d	-

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material induced a slight irritation being reversible within 14 days of dosing.
Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the Directive 67/548/EEC.

Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of different concentration of test material (undiluted, 20, 10, 5, 1 % in EtOH/DEP 1:1) were dermally applied on the clipped skin of the dorsal surface of the trunk of 4 New Zealand White rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours and then rinsed with soap and warm water. Animals were then observed for 14 days for oedema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after the removal of the patch and on day 7 and 14.

The mean scores calculated over all the animals tested with the undiluted test material within 3 scoring times (24, 48 and 72 h) were 1.58 for erythema and 0.08 for oedema.

Slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarly slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed.

On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

 

Under the test conditions, the test material induced a slight irritation being reversible within 14 days of dosing.

Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In the dermal irritation study of Aarup, performed according to the OECD guideline No. 404, and in compliance with GLP, the mean scores calculated over all the animals tested with the undiluted test material within 3 scoring times (24, 48 and 72 h) were 1.58 for erythema and 0.08 for oedema. Slight to well defined erythema was observed 1 to 72 hours after termination of exposure of 100% and 20% concentration of test article. Similarly slight erythema was observed 1 to 72 hours alter termination of exposure of 10%, 5% and 1% concentration of test article. Slight oedema was only observed in 1 rabbit 48 hours after termination of exposure of 100% and 20% concentration of test article. Thereafter no oedema was observed. On day 7 and 14 dose related accumulations of scales were observed in all rabbits. On day 14 the skin of all rabbits was intact.

In the dermal irritation study of Leuschner, conducted on the supporting substance (EC 422 -320 -3), and also performed according to the OECD guideline No. 404, and in compliance with GLP, similar results were drawn. The mean scores calculated for each animal tested within 3 scoring times (24, 48 and 72 h) were 1.0 / 1.3 / 1.0 for erythema and 1.0 / 1.0 /1.0 for oedema. Induration of the skin was observed in all animals 5 and 6 days after patch removal. Laceration of the skin was observed in one animal 5 and 6 days after patch removal. Peeling of the skin was observed in one animal 6 days, in another animal 5 and 6 days after patch removal. All the skin lesions were fully reversible at the end of the observation period (Day 7). This study is used for comparative purpose only (read across-justification), as a key study is available on the substance itself.

 

Eye irritation:

No studies were located on Pentadecan-15 -olide, therefore, a weight of evidence approach using the two studies conducted on the supporting substance (EC 422 -320 -3) was used to conclude on this endpoint. This read-across is justified is Iuclid section 13. In the two eye irritation studies performed according to the OECD test guideline No. 405 / E.U. method B.5, and in compliance with GLP, the test material was not irritating to the eye of rabbits. In the study of Chubb, the calculated mean score for each individual lesion for all 4 animals within 3 scoring times (24, 48 and 72 h) were 0.00 for chemosis, redness, discharge, iris and corneal lesions. In the study of Leuschner, the calculated mean score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 h) were 0.00 / 0.33 /0.00 for redness, and 0.00 / 0.00 /0.00 for chemosis, discharge, iris and corneal lesions.

Justification for selection of skin irritation / corrosion endpoint:
One study available on the substance itself (Aarup, 1994), GLP-compliant and of high quality (Klimisch score = 1). The same conclusion was drawn with the supporting substance (EC 422-320-3) (Leuschner, 2004).

Justification for selection of eye irritation endpoint:
No study was available on the substance itself, therefore, a weight of evidence approach using two reliable studies conducted on the supporting substance (EC 422-320-3) (Leuschner, 2004 & Chubb, 1992) was selected as the best strategy to conclude on toxicological properties.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self-classification:

Based on the available information no additional self-classification is proposed regarding both skin and eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.