2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

04 August 2003 - 14 August 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD test guidance in compliance with GLP and reported with a valid GLP certificate. The study is read across to an analogous substance; refer to image and further information below.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Annex V

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

144971-11-9

IUPAC Name:

144971-11-9

Test material form:

liquid: viscous

Details on test material:

CAS Number: 144971-11-9
Description: Clear colourless liquid
Batch: D21287
Purity: >99%
Test substance storage: At room temperature in the dark
Stabilty under storage conditions: Not indicated
Expiry date: 01 September 2003

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, GermanyNo. of animals: 3 Males.Age and bodyweight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.Identification: Earmark.ConditionsAnimals 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: 18.1 - 23.9°C), a relative humidity of 30-70% (actual range: 44 -81%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.AccommodationIndividually 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.DietStandard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.WaterFree access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 ML

Duration of treatment / exposure:

4 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

This eye irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special atlention was paid to the eyes, which were free from any abnormality.Each animal was treated by instilation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pullng 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 7.0) 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.OBSERVATIONSMortality/Viability: Twice daily.Toxicity: At least once daily.Body Weight: Day of treatment (prior to instilation) and at termination.Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instilation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Max. score:

1

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 7

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 8

Irritation parameter:

chemosis score

Max. score:

1

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 12

Irritation parameter:

cornea opacity score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Results 13

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 14

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 15

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 16

Irritation parameter:

iris score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

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 was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instilation revealed no corneal epithelial damage in any of the animals.

Other effects:

CorrosionThere was no evidence of ocular corrosion.Colouration I RemnantsNo staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.Toxicity I MortalityNo 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:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.

Executive summary:

Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.