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

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Remarks:

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

Type of study:

Buehler test

Justification for non-LLNA method:

We needed the non-LLNA method for a registration in China.

Specific details on test material used for the study:

N/A

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Beijing Vital Rive Laboratory Animal Technology Co., Ltd., China
- Age at arrival: 28 to 41 days
- Weight at study initiation: 334.98 g (mean weight of the test animals); 340.6 g (mean weight of the control animals)
- Housing: Animals were housed in plastic cage (80cmx50cmcx20cm) which held 10 to 12 animals with cob bedding during the study period. Animals used for preliminary irritation test were housed in a seperate cage after grouping.
- Diet (e.g. ad libitum): pellet rodent diet with complete nutrition supplied by Beijing Keaoxieli Feed Co. Ltd.
- Water (e.g. ad libitum): was purified by HT-R01000 purity system
- Acclimation period: 5 - 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-25 (target value 17-23 °C)
- Humidity (%): 39-64 % (target value 30-70 %)
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12

Route:

other: topical

Vehicle:

unchanged (no vehicle)

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

No. of animals per dose:

test group: 20 animals
control group: 10 animals

Details on study design:

RANGE FINDING TESTS:
Select two animals at random from all the animals. Directly apply 0.2 mL of neat test item to the animal to determine whether it has a skin irritating effect. No irritaiton was found, so the neat test item was selected for both induction and challenging.
Remove the fur by clipping the two flanks of the midline of each animal prior to the application. Put 0.2 mL neat test item on a piece of filter paper (about 2 cmx2cm) to each side of clipped area of the animal, and place a piece of patch (a gauze which was stuck to one layer non-allergenic medical adhesive tape). And then the patch was wrapped with the non-allergenic medical adhesive tape for 6 hours.
After 6 hours of exposure, the patch was removed and residual test item were removed by cotton wool soaked in water.
In the morning of the next day after exposure day, the dosing area was observed for local reactions.

MAIN STUDY
A. INDUCTION EXPOSURE
The left flanks of guinea pigs were clipped free of hair the day prior to each induction. The right flanks of guinea pigs were clipped free of hair the day prior to each challenging. Clear area was about 3 cmx3cm.
Once each week for three weeks (on Day 0 (first inducition date), day 7 and day 14) put 0.2 mL test item on a piece of filter paper (about 2cmx2cm) to the left side of clipped area of the animal, and place a piece of patch (a gauze which was stuck to one layer non-allergenic medical adhesive tape). And then the patch was wrapped with the non-allergenic medical adhesive tape for 6 hours.
- No. of exposures: 3
- Exposure period: 1st exposure (day 0): topical exposure (4 cm²) 6 hours; 2nd exposure (day7): topical exposure for 6 hours; 3rd exposure (day14): topical exposure for 6 hours
Clnical observation and scoring: at approximately 24 and 48 hours after each inducition, the guinea pigs were observed and scored for erythema and edema.


B. CHALLENGE EXPOSURE
On day 28, the test item was applied to the right site of the depilated back of each animal for both treated group and control group. The operation procedure was the same as the induction phase.
At approximatedly 21 hours and 45 hours after removing the patch, the challenge area was depilated of hair. At approximately 24 and 48 hours after removing the patch, the guinea pigs were observed and scored for erythema and edema.

- No. of exposures: 1
- Day(s) of challenge: on day 28
- Exposure period: dermal application for 6 hours
- Test groups: undiluted test substance (2 x 2 cm patch)
- Control group: undiluted test substance (2 x 2 cm patch)
- Site: left flanks
- Concentrations: 100% v/v
- Evaluation (hr after challenge): 24 and 48 hours after application

Challenge controls:

see above B. Challenge exposure

Positive control substance(s):

yes

Remarks:

2,4-Dinitrochlorobenzene (DNCB)

Positive control results:

Historical data, skin sensitisation result of positve control, DNCB, in the labs center:
The treated animals had an incidence of 18/20 after 24 and 48 h.
The control animals had an incidence of 1/12 after 24 and 48 h.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

not reported

No. with + reactions:

17

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

not reported

No. with + reactions:

13

Total no. in group:

20

RESULTS OF PILOT STUDY: no irritation at concentrations of 100% test substance

RESULTS OF TEST:

There were no deaths or morbidity during the test.

No abnormalities were found during the induction phase.

No abnormalities were found on the control animals and treated animals observed at 24 and 48 hours observation.

The incidence of skin sensitisation was 0 (0/20) for both 24 h and 48 h observation.

All of the animals showed expected gains in body weight during the test.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl ester is not a skin sensitiser.

Executive summary:

The study was designed to determine the potential for 1,2,4 -Benzenetricarboxylic acid, mixed dodecyl and octyltriesters to elicit a skin sensitisation reaction according to OECD 406. This study contained preliminary skin irritation test and main skin sensitisation test. Two animals were used to select highest non-irritating concentration and mild to moderate concentration in the preliminary skin irritation test. Thirty animals were used in the main skin sensitisation test, which included one control group (10 animals) and one treated group (20 animals). In the challenging phase, on day 28, 0.2 mL neat test item was dosed to the right flank of each animal of control group and treated group. 24 and 48 hours after the patch was removed in each induction the skin reactions were observed. Twenty four hours and forty eight hours after the patch was removed in challenging the skin reactions were observed and scored. Animals were weighed on the day prior to the first induction dose, and at the conclusion of the study.

There were no deaths or moribund during the test.

No abnormalities were found during the induction phase.

No abnormalities were found during on the control animals and treated animals observed at 24 h and 48 h.

The incidence of skin sensitisation is 0 (0/20) for both 24 h observation and 48 h observation.

All of the animals showed expected gains in body weight during the test.

Based on above results, the test item was not considered to cause sensitisation to guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitising properties of 1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters were determined in an OECD 406 Buehler assay, conducted for a regulatory region outside of EU.

1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters was determined not to be a skin sensitiser

Respiratory sensitisation

Endpoint conclusion

Additional information:

An OECD 406 Buehler study was conducted to determine the skin sensitisation potential of 1,2,4 -Benzenetricarboxylic acid, mixed dodecyl and octyltriesters. The highest non-irritating concentration was determined to be 100 % (neat). There were no deaths or moribund during the test. No abnormalities were found during the induction phase.

No abnormalities were found during on the control animals and treated animals observed at 24 h and 48 h. The incidence of skin sensitisation is 0 (0/20) for both 24 h observation and 48 h observation. Based on above results, the test item was not considered to cause sensitisation to guinea pigs.

Justification for classification or non-classification

No classification for sensitisation 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 1272/2208).