Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters when applied to rabbit skin and eye did not cause irritation

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
the temperature was above control (17-23 °C), at the 24 h confirmatory test dosing time for 2 animals was earlier than 4 h, no impact on study results
GLP compliance:
yes (incl. QA statement)
Remarks:
Health Care Inspectorate of Health, Welfare and Sport, Den Haag, The Netherlands
Specific details on test material used for the study:
N/A
Species:
rabbit
Strain:
other: Japanese White
Details on test animals or test system 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: 1602.5-2050.4 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
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
72 h (no irritation after 72 h)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right back, application of the test substance on a skin area of approx. 6 cm²
- Type of wrap if used: semi-occlusion with a gauze patch (2.5 cm x 2.5 cm). The patch was secured in position by an elastic bandage.

Approximately 24 hours before the test, the back and flanks of each animal was clipped free of fur. Only animals with healthy, intact skin by gross observation were used for the study. Cleared area was approximately 6cm x 6 cm. Two sites (2.5cm x 2.5cm) below the suprascapular area, on each side of the mid-line were selected as application sites. The other site (A) was served as a control site. One site (B) was designated as the test substance application site.

Approximaltely 0.5 ml of the test item was applied to the gauze patch (2.5cm x 2.5cm) on non-irritating adhesive tape covered by medical film. The control site (A) was covered with an untreated patch. The treated patch was placed over on the right back of clipped area (B). The skin was secured by using elastic bandage and medical paper tape to have a good contact with skin and to prevent animals from ingestion or inhalation of the test substance. All animals were kept in a semi-occlusive dressing for 4 hours.

Patches were removed after 4 hours. The residual test substance was gently wiped off the application site by cotton moistened with tepid water.

Skin reactions: Dermal observations for erythema, eschar and edema formation were conducted and recorded immediately and at 1, 24, 48 and 72 hours after patch removal. Because there were no dermal irritation in any animal at 72 h, no further observation was required.


SCORING SYSTEM: according to OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 0
- Edema: 0
Other effects:
N/A

All animals showed expected gain in body weight during the course of the study.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl triesters did not produce any evidence of skin irritation and corrosion in Japanese White rabbits.
Executive summary:

The study was performed to assess the acute dermal irritation/corrosion of 1,2,4 -Benzenetricarboxylic acid, mixed dodecyl and octyl ester in Japanese White Rabbits according to OECD 404. Three male rabbits were used for the study. A quantity of 0.5 ml test item was applied to right side of back skin of each animal for an exposure period of four hours. The untreated skin on the left back area of the animal served as the control. Observations of treated skin response were conducted immediately and at 1, 24, 48 and 72 hours after patch removal. Body weights were collected during this test.

No evidence of skin irritation was noted during the study with the mean scores of skin reactions of 0 at 24, 48 and 72 hours after patch removal. No abnormal clinical signs were noted and all animals showed expected gain in body weight during the course of the study.

The test item 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl triesters did not produce any evidence of skin irritation and corrosion in Japanese White rabbits.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
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
Specific details on test material used for the study:
N/A
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
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
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
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.

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

 

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

The skin and eye irritation properties of 1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters have been determined in the rabbit. The OECD 404 study showed no irritation to skin and OECD 405, no irritating effects in rabbit eyes.


Justification for classification or non-classification

No classification for skin or eye irritation or corrosion is indicated according to the general classification and labeling requirements for dangerous substances and preparations (67/544 EEC) or the classification, labeling and packaging (CLP) regulation (EC 1272/2008).