2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented experiment according to GLP and EC and OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

EC Number:

408-200-3

EC Name:

2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

Cas Number:

63187-91-7

Molecular formula:

C13H24O3

IUPAC Name:

[9-methyl-6-(propan-2-yl)-1,4-dioxaspiro[4.5]decan-2-yl]methanol

Test material form:

other: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species: New Zealand White, SPF-quality
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 15 weeks
- Weight at study initiation: 2489-2733 g
- Housing: individually, cages with perforated floors and equiped with automated drinking system
- Diet (e.g. ad libitum): Standard laboratory diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands); approx. 100 g/day
- Water (e.g. ad libitum): Tap water diluted with decalcified water, ad libitum
- Acclimation period: at least 5 days before start of treatment under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 55%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 (artificial fluorescent light)
Fluctuations from these optimal conditions were noted, but were considered to not have affected the study integrity.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 (all females)

Details on study design:

Approx. 24 hours before treatment, the dorsal fur was shaved with electric clippers, exposing an area of approx. 100 square centimeters (10 cm x 10 cm).

Prior to test substance administration, the animals were physically examined and the shaved area of skin to be treated was normal.

On test day 1, 0.5 mL of the test substance was applied to the intact skin of the shaved area on one flank, using a surgical gauze patch 2 x 3 cm mounted on Micropore tape (3M, St. Paul, USA). The contralateral flank was similarly prepared, but without test substance, to act as a procedural control. The dressing was wrapped around the abdomen and secured with an elastic bandage (Corban, 3M, St. Paul, USA).

Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap water and subsequently a dry tissue. However, the treated skin area remained sticky after removal of the test substance.

In order to facilitate the scoring, the skin area concerned of all animals was re-shaved before the observation on days 2, 3, 4, 7 and 14.

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24-48-72h

Score:

4.2

Max. score:

8

Reversibility:

fully reversible within: 14d

Irritant / corrosive response data:

There was no evidence of a corrosive effect on the skin.
No staining of the treated skin by the test substance was observed.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The observed irritation resulted in a PPDI of 4.2 when applied to the intact rabbit skin. When compared to the EEC criteria for classification and labelling for dangerous susbtances (DPD), the test substance should be classified as a skin irritant (moderately irritating).

Executive summary:

The study assesses the possible irritation or corrosion potential of the test substance in the rabbit according to OECD and EEC guidelines. The test substance was applied onto shaved skin of 3 female albino rabbits using semi-occlusive dressing for 4 hours, followed by 6 observations at approx. 1, 24, 48 and 72 hours, and 7 and 14 days after removal of the dressings and remaining test substance.

 

Under the conditions of the test, the test substance resulted in well-defined erythema and slight or moderate oedema. The skin irritation was reversed within 14 days after exposure in all 3 animals. No corrosive effect occurred on the skin in all 3 rabbits. In the area of application, no staining of the treated skin by the test substance was observed. No signs of systemic intoxication were observed during the study period.

 

The test substance resulted in a primary irritation index of 4.2 (moderately irritating) when applied to intact rabbit skin.