Pentadecan-15-olide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

2004-10-04 to 2004-10-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study performed according to OECD test guideline No. 402 and in compliance with GLP. The study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across. The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 1987-02-24

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2000-08-02

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: (E)-oxacyclohexadec-12-en-2-one; (E)-oxacyclohexadec-13-en-2-one; a) (Z)-oxacyclohexadec-(12)-en-2-one and b) (Z)-oxacyclohexadec-(13)-en-2-one

EC Number:

422-320-3

EC Name:

A mixture of: (E)-oxacyclohexadec-12-en-2-one; (E)-oxacyclohexadec-13-en-2-one; a) (Z)-oxacyclohexadec-(12)-en-2-one and b) (Z)-oxacyclohexadec-(13)-en-2-one

IUPAC Name:

422-320-3

Test material form:

other: liquid

Details on test material:

- Chemical name: E/Z-Oxacyclohexadec-12/13-en-2-one
- Physical state: clear, colourless to light yellow liquid
- Storage condition of test material: cool, in full tightly closed containers, in a dark place
- Density: 0.9462 g/mL (according to LPT laboratory identification)

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of adaptation: males: 49 days; females: 64 days
- Weight at dosing: males: 226 - 255 g; females: 210 - 219 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week; kept singly in MAKROLON cages (type III)
- Diet: ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C +/- 3 °C (maximum range)
- Relative humidity: 55 % +/- 15 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the hair on the site of application was clipped with hair clippers without causing injury approximately 24 hours before administration. The site was situated on the animals back between the fore and hind extremities and had an area of at least 5 X 6 cm (approx. 1/10 of body surface).
- Type of wrap if used: the test item was applied to 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster on the application site.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure period no residual test item had to be removed.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the administration volume was 2.11 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration.
During the follow-up period (two weeks), changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on mortality were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes; at the end of the experiments, all surviving animals were sacrificed, dissected and inspected macroscopically.
No microscopic examination was performed as no gross pathological changes were recorded.
- Other examinations performed: the skin was observed for the development of erythema and oedema and was rated according to the Draize scale.

Statistics:

As no mortality did occur no LD50 could be calculated.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of toxicity.

Gross pathology:

No macroscopical changes were noted at necropsy.

Other findings:

- Other observations: no skin reactions were observed.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50Combined > 2000 mg/kg bw. Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

Executive summary:

In a limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, groups of young adult Crl:CD(SD) rats (5/sex) were occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality occurred during the study and no clinical signs were observed. The animals gained the expected weight throughout the whole study period. No macroscopical changes were noted at necropsy. No skin reactions were observed.

Dermal LD50 Combined > 2000 mg/kg bw

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).