1,2,4-Benzenetricarboxylic acid, mixed lauryl and octyl triesters

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.4.2015 - 26.4.2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Remarks:

Health Care Inspectorate of Health, Welfare and Sport, Den Haag, The Netherlands

Test material

Test material information

Constituent 1

Reference substance name:

1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octy triesters

IUPAC Name:

1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octy triesters

Constituent 2

Reference substance name:

tris(mixed dodecyl and octyl)benzene-1,2,4-tricarboxylate

EC Number:

700-342-7

Cas Number:

1163775-81-2

Molecular formula:

C14H47O6 to C18H55O6

IUPAC Name:

tris(mixed dodecyl and octyl)benzene-1,2,4-tricarboxylate

Constituent 3

Reference substance name:

Linplast 812 TM

IUPAC Name:

Linplast 812 TM

Specific details on test material used for the study:

N/A

Test animals / tissue source

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Shenyang pharmaceutical University Experimental Animal Center (Liaoning, P.R. China)
- Age at study initiation: young adult (at receipt 84-140 days)
- Weight at study initiation: 1730.9-1933.8 g
- Housing: single housing in suspended, stainless wire cages (50cmx35cmx30 cm) on cage racks (167cmx70cmx171cm)
- Diet (e.g. ad libitum): pellet breeding rabbit diet, ad libitum
- Water (e.g. ad libitum): Water was purified using the HT-R01000, ad libitum
- Acclimation period: 9 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-26.1
- Humidity (%): 40-56
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72 h

Duration of post- treatment incubation (in vitro):

N/A

Number of animals or in vitro replicates:

3

Details on study design:

Approximately 24 hours prior to dosing, both eyes of each animal were examined with binocular loupe and 2 % aqueous of sodium fluorescein (vehicle: physiological saline) was placed in the conjunctivae sac of both eyes, and then eyes were washed by using physiological saline after 15 seconds. Corneas of both eyes were examined in the slit lamp to see whether there was fluorescin detention in the cornea or not. No eye abnormalitities were noted for all treated eye prior to test.
The rabbit was held firmly but gently until quiet. 0.1 ml of the test item was placed in the conjunctival sac of right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were gently held together for approximately one second in order to prevent loss of the material. The left eye remained untreated and served as control.

The treated eyes of each animal were examined by using a binocular loupe at approximately 1, 24, 48 and 72 hours after treatment. Because there were no ocular irritations in 3 animals at 72 hours, no further observation was required. Any other lesions in the eye also were reported. At each observation point discharge and the area of cornea opacity was also recorded, but not scored.

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: binocular loupe, further examination with fluorescein sodium and slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 4

Irritation parameter:

cornea opacity 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 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One animal showed fluorescein retention at 24 h observation point and recovered at 48 h observation point. No abnormality was found in eye except above signs. The maximum mean scores of cornea, iris, conjunctivae redness and swelling from 24 h to 72 h were 0.3, 0, 0, 0, respectively.

Other effects:

one animal showed decreased bodyweight and the other two animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	0/0/0	0/0/0	0/0/0
24 h	0/1/0	0/0/0	0/0/0	0/0/0
48 h	0/0/0	0/0/0	0/0/0	0/0/0
72 h	0/0/0	0/0/0	0/0/0	0/0/0
Average 24h, 48h, 72h	0.3	0	0	0
Area effected	-	-	-	-
Reversibility*)	c	-	-	-
Average time (unit) for reversion	48 hours	-	-	-

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl triester produced maximum mean scores of 0.3 in Japanese White rabbit eye.

Executive summary:

The study was performed to assess the acute eye irritation/corrosion of 1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters in Japanese White rabbits according to OECD 405.

Three male rabbits were used for the study. Each animal was administered 0.1 ml of the test item into right eye. Untreated left eye served as the control. Eye reactions were observed immediately, and at 1h, 24h, 48h and 72 h after administration and mean scores were calculated at 24, 48 and 72 hours after administration. Individual animal body weights were collected during the test. Three treated animals showed frequently blinking at initial reaction observations. Above signs recovered to normal in 4 to 5 hours after dosing. Except above signs, no other abnormal signs were observed in any animals during the study. One animal showed fluorescein retention at 24 h observation point and recovered at 48 h observation point. Except above signs, no other abnormal signs in eye were observed. The maximum mean scores of cornea, iris, conjunctivae redness and swelling at 24h, 48h and 72h were 0.3, 0, 0, 0. One animal showed decreased bodyweight and the other two animals showed expected gain in bodyweight during the study.

The test item 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl triester produced maximum mean scores of 0.3 in Japanese White rabbit eye.