tris(2-octyldodecyl) citrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 February 1993 to 4 March 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3-tris(2-octyldodecyl) 2-hydroxypropane-1,2,3-tricarboxylate

EC Number:

603-121-2

Cas Number:

126121-35-5

Molecular formula:

C66H128O7

IUPAC Name:

1,2,3-tris(2-octyldodecyl) 2-hydroxypropane-1,2,3-tricarboxylate

Test material form:

liquid

Details on test material:

Tris(octyldodecyl) citrate 99.87 %
Bis(octyldodecyl) citrate 0.13 %

Specific details on test material used for the study:

Identification: Citmol 320, clear liquid.
Storage: Test material was stored at room temperature in the container in which it was received.
Reserve sample: Remaining sample of the test material was returned to the sponsor at the end of the study.
Test material formulation: The test material was dosed as supplied.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals utilised
Number of animals/sex/dose: 5
Number of groups 1
Number of animals/groups 10

Test animals
Species: Rabbits
Strain: New Zealand White
Sex: Male and Female (females nulliparous and non-pregnant)
Age (at receipt): 10 – 12 weeks
Weight range (at study initiation): Male (2.0 – 3.0 kg), Female (2.0 – 3.0 kg)
Number/sex/dose level: 5
Supplier: Gingrich Animal Supply, Fredricksburg, PA 17026, USDA # 23-B-007
Identification: Animals placed on test were individually identified by a number on the right ear and a corresponding cage label.

Husbandry
Diet: Standard laboratory feed for rabbits; food and city water were available as libitum.
Housing: Animals were housed individually in suspended stainless steel wire mesh cages in a room controlled for temperature (targeted at 21 °C ±2 ׄC.
Acclimation: Animals were acclimated to the testing facility at least 4 days prior to the start of testing. Animals were observed for general health and suitability for testing during this period.

Administration / exposure

Type of coverage:

other: Non-occlusive.

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Site preparation:
Animals were clipped free of fur at the test site 24 hours prior to application of the test material. Only animals with healthy intact skin were used.


Sample preparation:
The test material was dosed as supplied.

Application:
The test material was applied as a uniform film covering approximately 10 % of the total body surface area and covered with a gauze patch. The gauze was held in place with non-irritating tape, covered with a non-occlusive dressing then over-wrapped with additional non-irritating tape.
The test material was applied to the clipped intact skin of the dorsal area of the trunks of five male and five female rabbits.

Duration of exposure:

Exposure duration:
The skin was exposed to the test material for a period of 24 hours. After the 24 hour exposure period, the patches and residual test material were removed. A dry paper towel was utilised to remove and test material which adhered to the skin.

Doses:

Dose level: A dose of 2 g/kg body weight was administered as a limit test.
Frequency: Once
Test duration: Observations were taken seven days a week for 2 weeks.
Dose calculation: The single volumetric dose was calculated using the following equation: Dose volume (ml) = [animal weight (kg) x limit dose (2 g/kg)] / test material density (gm/ml). The dose volume was measured using a syringe.

Details on study design:

In-life observation

Body weight:
Body weight was recorded in kilograms for each animal just prior to test substance exposure, at seven days, and at scheduled sacrifice. Rabbits with initial body weights between 2.0 kg and 3.0 kg were used.

Signs of toxicity and mortality:
All test animals were observed for signs of toxicity and mortality daily, seven days a week for two weeks. Observations included the following; circulatory, autonomic and central nervous systems, somatomotor activity and behaviour patterns.

Post-mortem observations:
All test animals were sacrificed with sodium pentobarbital and a gross necropsy was performed on all animals 14 days after exposure.

Statistics:

Statistical evaluation of the study was not considered necessary.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities occurring during the 14 day study period.

Clinical signs:

other: Dermal observations: On day 1, two of five males and one of five females had very slight erythema and very slight edema; two males and three females had very slight erythema and no edema; one female had well-defined erythema and no edema. One male had no

Gross pathology:

There were no gross abnormalities observed in any of the animals at necropsy.

Any other information on results incl. tables

RESULTS

Table 1: Body weight data

Rabbit #	Sex	Day 0 Initial Weight (kg)	Day 7 Intermediate Weight (kg)	Day 14 Final Weight (kg)
9971	M	2.6	2.9	3.0
9977	M	2.6	2.6	2.7
9984	M	2.5	2.7	2.8
9985	M	2.7	3.0	3.1
9990	M	2.4	2.5	2.8
9997	F	2.5	2.8	3.2
10006	F	2.4	2.7	2.8
10001	F	2.6	2.7	2.8
10015	F	2.5	2.9	3.1
10016	F	2.7	3.0	3.1

 

Table 2: Erythema/edema

		24 hours		14 days
Rabbit #	Sex	Ery	Ede	Ery	Ede	Mortality
9971	M	1.0	1.0	0.0	0.0	Alive
9977	M	1.0	1.0	1.0	0.0	Alive
9984	M	1.0	0.0	0.0	0.0	Alive
9985	M	0.0	0.0	0.0	0.0	Alive
9990	M	1.0	0.0	0.0	0.0	Alive
9997	F	1.0	0.0	0.0	0.0	Alive
10006	F	1.0	0.0	0.0	0.0	Alive
10001	F	1.0	0.0	0.0	0.0	Alive
10015	F	1.0	1.0	0.0	0.0	Alive
10016	F	2.0	0.0	0.0	0.0	Alive

Number of animals treated: 10

Number of animals survived: 10

Ery = Erythema

Ede = Edema

 

Table 3: Gross necropsy

 

Rabbit #	Sex
9971	M	No gross abnormalities observed
9977	M	No gross abnormalities observed
9984	M	No gross abnormalities observed
9985	M	No gross abnormalities observed
9990	M	No gross abnormalities observed
9997	F	No gross abnormalities observed
10006	F	No gross abnormalities observed
10001	F	No gross abnormalities observed
10015	F	No gross abnormalities observed
10016	F	No gross abnormalities observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this guideline (OECD 402) study conducted with GLP certification, the acute dermal LD50 of the test material (EC 603-121-2) to the rabbit was determined to be >2,000 mg/kg bw (both sexes). The test material was administered under non-occlusive conditions as a limit test (2,000 mg/kg bw) to male and female for 24 hours, with a post application observation period of 14 days. The result of the test does not trigger classification of the test material as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

The test material produced very slight to well-defined erythema and very slight edema during the 14 day study period.
Ten of ten animals survived a topical application at a dose of 2 g/kg of the test material at the fourteenth day. The dermal LD/50 is determined to be greater than 2 g/kg.
The test material is not considered to be toxic at 2 g/kg.

Executive summary:

The purpose of this guideline (OECD 402) acute dermal toxicity, limit test study was to determine the potential toxic characteristics of substance EC 603-121-2 by a single dermal application to rabbits. Data from this study may be used as a basis for classification labelling and the establishment of dosage requirements for subsequent toxicity testing.

Five male and five female New Zealand White Rabbits were dosed with a topical application of EC 603-121-2 at a dose of 2.0 g/kg body weight.

The test material was applied, under non-occlusive conditions, to the clipped intact skin of the dorsal area of the trunks of five male and five female rabbits.

The test material produced very slight to well-defined erythema and very slight edema during the 14 day study period.

Five of five males and five of five females dosed survived the course of the study and were sacrificed and necropsied at the end of the 14 day observation period.

The acute dermal LD50 of the test material (EC 603-121-2) to the rabbit was determined to be >2,000 mg/kg bw (both sexes). The result of the test does not trigger classification of the test material as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

The test material is not considered to be toxic at 2 g/kg.