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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2000-05-09 - 2000-06-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1992-07-17)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(1992-12-29)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(August 1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Directive (67/548/EEC), 7th Amended Directive (92/32/EEC) dated 30 April 1992 and EEC Directive 93/21/EEC, 27 April 1993
Deviations:
no
Qualifier:
according to
Guideline:
other: Gefahrstoffverordnung (GefStoffV) of 29 September 1994 (BGBl.1, p. 2557)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): ATEHC
- Physical state: liquid
- Expiration date of the lot/batch: 1 November 2000
- Storage condition of test material: at room temperature
- Other: Chemical name (as specified by the Sponsor): acetyl-tri-(2-ethylhexyl)-citrate

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: Before the animals arrived, the study room and cages were cleaned and disinfected. During the study, the room and cages were cleaned at regular intervals. The rabbits were kept individually in a battery of cages with a cage size of 50 x 45 x 40 cm (L x B x H), equipped with a paper disposal system.
- Diet (e.g. ad libitum): Pelleted breeding, offered ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Weight at study initiation: 3.20, 3.28 and 3.49 kg
- Acclimation period: 12 and 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): between 30 and 70 %
- Air changes (per hr): 16 times per hour and filtered adequately
- Photoperiod (hrs dark / hrs light): Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: skin was clipped 24 h before treatment
Vehicle:
unchanged (no vehicle)
Controls:
other: one untreated region of the same animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of the test substance
Duration of treatment / exposure:
4h
Observation period:
up to 72h after the end of exposure
Number of animals:
3 male animals
Details on study design:
The liquid test substance was used undiluted. One of the animals (rabbit no. 1) was treated with 0.5 mL of the test item on each of three patches, which were applied to different regions of the back, one untreated region served as control. The test substance was applied to the three gauze patches and then applied to the skin. The closed patch exposure was effected by means of a semi-occlusive bandage, non-irritating tape and Stulpa, which enveloped the whole of the animal's trunk. Exposure durations were 3 min, 1 h and 4 h. Since there was no response to the application of the test substance at each time point, the further two animals were treated subsequently in the same manner with an exposure duration of 4 h.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1 and #2
Time point:
other: 1h, 24h, 48h and 72h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1h and 24h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48h and 72h
Score:
0
Max. score:
1
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
other: 1h, 24h, 48h and 72h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The mean grades of skin reactions at 24, 48 and 72 h after the end of the exposure were lower than the value classified as irritant by the EEC Directive 93/21/EEC of 27 April 1993 and the Gefahrstoffverordnung (GefStoffV) of 29 September 1994 (BGB1. I, p. 2557). When applied to the skin, the test item "ATEHC, CAS-NO.: 144-15-0" may be classified as "non-irritant".
Other effects:
Clinical Observations: One hour after the end of the 4-hour exposure, very slight erythema was observed in one animal (no. 3). This finding was still apparent 24 h after exposure.
No other toxic effects than skin irritations were observed.

Any other information on results incl. tables

Grading of skin reaction (as stipulated by OECD 404)

Erythema and Eschar Formation  Grade
 No erythema  0
 Very slight erythema (barely perceptible)  1
 Well-defined erythema  2
 Moderate to severe erythema  3
 Severe erythema (beet redness) to eschar formation preventing grading of erythema  4

Maximum possible (both formations): 4

Oedema Formation  Grade
 No oedema  0
 Very slight oedema (barely perceptible)  1
 Slight oedema (edges of area well defined by definite raising)  2
 Moderate oedema (raised approximately 1mm)  3
 Severe oedema (raised more than 1mm and extending beyond area of exposure)  4

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The test substance can be regarded as non irritant according to the results of the study.
Executive summary:

The potential toxicity of acetyltri-2 -ethylhexylcitrate (ATEHC) was assessed in an acute dermal irritation/corrosion test on 3 male albino rabbits according to OECD 404 and EU method B.4 and in compliance with GLP (2000). To assess dermal reactions to the test substance, one of these animals was treated in advance. The test item was applied to gauze patches which were then applied to the skin. Three test patches were applied concurrently to the animal. The first patch was removed after 3 min, the second and third patch were removed after 1 h and 4 h, respectively. Since no skin reactions were observed, in the two further animals, 0.5 mL of the test substance was applied on the right side of the dorsal clipped region, the untreated left side served as control. Exposure duration was 4 h. Both sides were examined at 1, 24, 48 and 72 h after the end of exposure and the following results were obtained: Very slight erythema was observed in one animal (no. 3) 1 h after the 4-hour exposure. This finding was still apparent 24 h after exposure, but fully reversible within 48h. Subsequently, no findings were observed. Further no other toxic effects were observed.

It can be assumed that the same applies to tributyl citrate (CAS 77-94-1) as it is a near analogue to the test substance acetyltri-2 -ethylhexylcitrate (ATEHC).