Oxazolidine, diheptyl~

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September - October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

ANIMALS
- Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Harlan, Horst, The Netherlands.
- Number of animals: 3 males
- Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
- Identification: Earmark.
- Health inspection: A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

HUSBANDRY
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 21.4 - 24.0°C), a relative humidity bf 30-70% (actual range: 44 - 66%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
- Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiäten GmbH, Soest, Germany) approximately 100 grams per day. Hay (TecniLab-SMI SV, Someren, The Netherlands) was provided at least three times a week.
- Water: Free access to tap water.
Results of analysis for each batch of diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

n.a. (not rinsed)

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after
considering the degree of eye irritation observed in the first animal.
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes 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 (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. Since no residual test substance was seen, the treated eyes were not rinsed with tepid tap water.
After the final observation, the animals were sacrificed by intra-venous injection of pentobarbital Euthesate® (Ceva Sante Animale BV, Naaldwijk, The Netherlands).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Instillation of 0.1 mL of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness (grade 1) and discharge (grade 1). The irritation had completely resolved within 24 hours. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion.

Other effects:

No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
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:

GHS criteria not met

Conclusions:

The test substance does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Executive summary:

Acute eye irritation/corrosion study with Sa 34 in the rabbit

The study was carried out based on the guidelines described in:

OECD No 405 (2002) "Acute Eye Irritation / Corrosion"

EC, Council Directive 67/548/EEC, An. V, B.5, (2004) "Acute Toxicity: Eye Irritation / Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000); including the most recent partial revisions.

Single samples of 0.1 mL of the test substance were instilled into one eye of each of three rabbits.

Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours.

Based on these results the test substance does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of

Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).