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

Eye irritation

Administrative data

Endpoint:

eye irritation: 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

one single treatment

Observation period (in vivo):

22 days

Number of animals or in vitro replicates:

3

Details on study design:

STUDY DESIGN:
On day 1, prior to test substance administration, the animals were physically examined and the eyes were found to be normal. The test substance (0.1 mL per animal) was instilled in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated in all three animals on days 4, 8 and 15, and in two of three animals also on day 22. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

OBSERVATIONS:
- Viability / mortality / toxicity: daily
- Body weight: day 1 of test
- Irritation: 1h, 24h, 48h and 72 h and 7d, 14d and 21d after instillation of the test substance

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

other: mean over 24-48-72h

Score:

1.44

Max. score:

4

Reversibility:

not fully reversible within: 21d

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean over 24-48-72h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48h

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean over 24-48-72h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean over 24-48-72h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7d

Any other information on results incl. tables

Draize score calculation

#	Tissue	1h	24h	48h	72h	7d	14d	21d
673	Cornea	0	15	20	20	10	5	5
	Iris	5	5	0	0	0	0	0
	Conjunct.	10	14	14	10	2	0	0
	Subtotal	15	34	34	30	12	5	5
674	Cornea	0	20	10	10	20	0	0
	Iris	5	5	0	0	0	0	0
	Conjunct.	10	16	16	12	4	2	0
	Subtotal	15	41	26	22	24	2	0
675	Cornea	0	20	10	10	15	20	10
	Iris	5	5	0	0	0	0	0
	Conjunct.	12	16	14	12	2	2	2
	Subtotal	17	41	24	22	17	22	12

Calculations for EEC Classification

#	Time	Corneal Opacity	Iris Lesion	Conjunctival Redness	Conjunctival Chemosis
673	24h	1	1	3	2
	48h	1	0	3	2
	72h	1	0	3	1
	Mean	1.0	0.3	3.0	1.7
674	24h	1	1	3	2
	48h	2	0	3	2
	72h	2	0	3	1
	Mean	1.7	0.3	3.0	1.7
675	24h	1	1	3	2
	48h	2	0	3	2
	72h	2	0	3	1
	Mean	1.7	0.3	3.0	1.7

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the test substance was found to be an eye irritant.

Executive summary:

The study assesses the possible irritation or corrosion potential of the test substance to the rabbit eye according to OECD and EEC guidelines. A single dose of the test substance (0.1 mL) was instilled into one eye of each of 3 female albino rabbits, followed by 7 observations at approx. 1, 24, 48 and 72 hours, and 7, 14 and 21 days after test substance administration.

Under the conditions of the test, the test substance resulted in adverse effects on the cornea, iris and the conjunctivae in all 3 animals. The opacity of the cornea was reversed within 14 days in one animal and was not reversed within the study period in the other two animals. The injection of the iris was reversed within 48 hours in all three animals. The irritation of the conjunctivae was reversed within 14 days in one animal and within 21 days in a second animal, but was not reversed within the study period in the third animal. Ocular corrosion was not observed in any of the three animals. No signs of systemic intoxication were observed during the study period.

 

In conclusion, according to the EEC criteria for classification and labelling requirements for dangerous substances (67/548/EEC), the test substance is to be classified as an eye irritant.