Reaction product of mixed triesters of heptanoic acid (n-C7), nonanoic acid (n-C9) and trimethylolpropane (i-C7)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 to 14 August 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

144971-11-9

Cas Number:

144971-11-9

IUPAC Name:

144971-11-9

Constituent 2

Reference substance name:

Hatcol 3331

IUPAC Name:

Hatcol 3331

Test material form:

other: clear colourless liquid

Details on test material:

Identification: Hatcol 3331
CAS Number: 144971-11-9
Description: Clear colourless liquid
Batch: D21287
Purity: 97.3%
Test substance storage: At room temperature in the dark
Stability under storage conditions: Not indicated
Expiry date: 01 September 2003
Specific Gravity: 0.969-0.976

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, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and bodyweights were at least 1.0 kg.
Identification: Earmark.

ANIMAL 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: 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.
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: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromln, Lage, Germany) approx. 100 g per day.
Water: Free access to tap-water.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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.

Duration of treatment / exposure:

24 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 attention was paid to the eyes, which were free from any abnormality.
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 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.

OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
The irritation was assessed according to the following numerical scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation: 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 instillation revealed no corneal epithelial damage in any of the animals.
Corrosion: There was no evidence of ocular corrosion.

Other effects:

Colouration/Remnants: No staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.
Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

INDIVIDUAL EYE IRRITATION SCORES

Time after dosing	Cornea			Iris	Conjunctivae			Comments
	Opacity	Area	Flour area (%)		Redness	Chemosis	Discharge
No 518# (Sentinel)
1 hour	0	0		0	1	1	0
24 hours	0	0	0	0	0	0	0
48 hours	0	0		0	0	0	0
72 hours	0	0		0	0	0	0
No 528#
1 hour	0	0		0	1	0	0
24 hours	0	0	0	0	0	0	0
48 hours	0	0		0	0	0	0
72 hours	0	0		0	0	0	0
No 529#
1 hour	0	0		0	1	0	0
24 hours	0	0	0	0	0	0	0
48 hours	0	0		0	0	0	0
72 hours	0	0		0	0	0	0

Flour area (%): green staining (percentage of total cornea area) after fluorescein treatment

 

MEAN VALUE EYE IRRITATION SCORES

Animal#	Mean 24 – 72 hours
	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
518	0	0	0	0
528	0	0	0	0
529	0	0	0	0

 

#Animal specifications:

Animal no	Sex	Age at start (weeks)	Bodyweights (grams)
			Prior to application	At termination
518	Male	7-9	1492	1705
528	Male	8-10	1807	1905
529	Male	8-10	1691	1768

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Not irritating

Executive summary:

Acute eye irritation/corrosion study with HATCOL 3331 in the rabbit.

The study was carried out based on the guidelines described in: EC Commission Directive92169/EEC, B.5, "Acute Toxicity - Eye irritation", OECD No.405, "Acute Eye Irritation/Corrosion"and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98-195, August 1998.

Single samples of 0.1 ml of HATCOL 3331 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 was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.