Decahydro-2-naphthyl acetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 May 2000 - 23 May 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The standard information requirements for REACH Annex VII substances for serious eye damage/eye irritation can be satisfied by an assessment of the available in vivo data, physicochemical properties (i.e. acid or alkali reserve) or in vitro eye irritation studies. Conducted prior to the validation and regulatory acceptance of alternative methods, the reliable (Klimisch 1) and GLP compliant in vivo Draize test was available for the test substance and considered sufficient to fulfil the information requirement.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Decahydro-2-naphthyl acetate

EC Number:

234-054-3

EC Name:

Decahydro-2-naphthyl acetate

Cas Number:

10519-11-6

Molecular formula:

C12H20O2

IUPAC Name:

decahydronaphthalen-2-yl acetate

Test animals / tissue source

Species:

rabbit

Strain:

other: Chbb:FIM(SPF) - Littlerussian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Species: Little Russian SPF albino rabbits (Chbb:HM(SPF))
- Sex: Females
- Source: BI Pharma KG, 88297 Biberach
- Weight at study initiation: 2.7 - 3.0 kg b.w.
- Housing: Rabbits were caged individually in PPO cages (floor area: 2576 sq.cm) with perforated floor
- Diet (e.g. ad libitum): Pelleted complete rabbit diet, ad libitum
- Water (e.g. ad libitum): Domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 10 times/hr
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL
- Purity: 98.9 %
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed with 20 ml 0.9% sodium chloride solution after Fluorescein was instilled.
- Time after start of exposure: The eyes were examined and the grade of ocular reaction was recorded one hour and 24 hours later. After the first 24 hour reading Fluorescein was instilled. The eyes were also examined 48 and 72 hours as well as 7 days after the treatment.

SCORING SYSTEM: Cornea reactions were scored both before and alter the instillation of Fluorescein.
- Opacity degree of density was evaluated on a scale of 0 (o ulceration or opacity) to 4 (complete corneal opacity, iris not discernible) and area of cornea involved was evaluated on a scale of 1 (one quarter (or less) but not zero) to 4 (more than 3 quarters, up to whole area).
- The iris was evaluated on a scale of 0 (normal) to 2 (no reaction to light, haemorrhage, gross destruction (any or all of these)).
- Conjunctiva redness (palpebral and bulbar conjunctivae excluding cornea and iris) was evaluated ona scale of 0 (vessels normal) to 3 (diffuse beefy red), chemosis was evaluated on a scale of 0 (no swelling) to 4 (swelling with lids more than half closed), and discharge was evaluated on a scale of 0 (no discharge) to 3 (discharge with moistening of the lids and hairs, and considerable area around the eye).

ASSESSMENT
- Scoring was evaluated in line with the directive of the Commission 93/21/EEC of May 4, 1993 which stated that “a substance of a preparation is considered to be irritant if it causes ocular lesions which occur within 72 hours after exposure and which persists for at least 24 hours. Ocular lesions are significant if the mean scores of the eye irritation test have any of the following values: Cornea opacity ≥2 but <3; Iris lesion ≥1 but <1.5; Redness of conjunctivae ≥2.5; Oedema of conjunctivae (chemosis) ≥2
A substance or a preparation is considered to be able to cause serious damage to eyes if it causes severe ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours”.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Remarks on result:

other: After instillation of Fluorescein, 24 hours after test item application, one animal had a cornea opacity score of 1.

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

1

Remarks on result:

other: One hour after application, two animals had an iris score of 1

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Discharge was observed in all animals 1 hour after test item application (max score = 2) and redness was observed in 3 animals up to 48 hours after test item application and in 1 animal up to 72 hours after test item application (max score = 2).

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Chemosis was observed in 2 animals up to 24 hours after test item application and in 2 animals up to 48 hours after test item application (max score = 2).

Irritant / corrosive response data:

Animal 1: A discharge with moistening of the lids and hairs just adjacent to lids (score = 2) was observed 1 hour after application of the test article. Diffuse, crimson red conjunctiva with individual vessels not easily discernible (score = 2) and a swelling above normal (score = 1) were observed 1 and 24 hours after application, and some conjunctival vessels definitely injected (score = 1) were observed 48 hours after application. Animal 1 was free of any signs of eye irritation at 72 hours after application.

Animal 2: An iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light (score = 1) and a discharge with moistening of the lids and hairs just adjacent to lids (score = 2) were observed at 1 hour after application. A diffuse, crimson red conjunctiva with individual vessels not easily discernible (score = 2) as well as an obvious swelling with partial eversion of lids (score = 2) were observed after 1 and 24 hours. Scattered or diffuse area of opacity on one quarter or less of cornea was observed after instillation of Fluorescein (score = 1). Conjunctival vessels definitely injected (score = 1) and swelling above normal.(score = 1) were observed at 48 hours and some conjunctival vessels definitely injected (score = 1) was observed at 72 hours. Animal 2 was free of any signs of eye irritation at 7 days after application.

Animal 3: An iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light (score = 1) and a discharge different from normal (score = 1) were observed 1 hour application. A diffuse, crimson red conjunctiva with individual vessels not easily discernible (score = 2) as well as an obvious swelling with partial eversion of lids (score = 2) were observed 1 and 24 hours after application. Conjunctival vessels definitely injected (score = 1) and swelling above normal (score = 1) were observed at 48 hours. Animal 3 was free of any signs of eye irritation at 72 hours after application.

Animal 4: A diffuse, crimson red conjunctiva with individual vessels not easily discernible (score = 2), a swelling above normal (score = 1) and a discharge different from normal (score = 1) were observed 1 hour after application. Swelling above normal (score = 1) was observed 24 hours after application and some conjunctival vessels definitely injected (score = 1) were observed 24 and 48 hours after application. Animal 4 was free of any signs of eye irritation at 72 hours after application.

Any other information on results incl. tables

Table 1. Individual mean eye irritation scores

Parameter	Animal 1	Animal 2	Animal 3	Animal 4
Cornea opacity, degree	0.00	0.00	0.00	0.00
Iris	0.00	0.00	0.00	0.00
Conjunctiva redness	1.00	1.33	1.00	0.67
Conjunctiva chemosis	0.33	1.00	1.00	0.33

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean scores of cornea opacity, iris lesion, conjunctiva redness and conjunctiva oedema (chemosis) were 0.0, 0.0, 1.0 and 0.7, respectively. All animals were free of any signs of eye irritation after 7 days.

Executive summary:

Eye irritation of the test item was tested in four female albino rabbits. An undiluted volume (0.1 mL) of the test item was administered one rabbit eye, whilst the other eye served as a control. Effects on the cornea, iris and conjunctiva were recorded at 1, 24, 48 and 72 hours and 7 days after application. The mean scores of cornea opacity, iris lesion, conjunctiva redness and conjunctiva oedema (chemosis) were 0.0, 0.0, 1.0 and 0.7, respectively. All animals were free of any signs of eye irritation after 7 days. According to the directive of the EEC commission 93/21/EEC (4 May 1993), the test item should not be classified as eye irritating.

 

Conducted according to OECD Guideline 405 and EU Method B.5 and GLP, the study was considered to be reliable without restriction (Klimisch 1).