Reaction product of mixed triesters of heptanoic acid (n-C7), nonanoic acid (n-C9) and trimethylolpropane (i-C7)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 to 18 July 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed inn accordance with OECD, EU & US EPA test guidelines in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

144971-11-9

Cas Number:

144971-11-9

IUPAC Name:

144971-11-9

Constituent 2

Reference substance name:

Hatcol 3331

IUPAC Name:

Hatcol 3331

Test material form:

other: clear colourless liquid

Details on test material:

Identification: Hatcol 3331
CAS Number: 144971-11-9
Description: Clear colourless liquid
Batch: D21287
Purity: 97.3%
Test substance storage: At room temperature in the dark
Stability under storage conditions: Not indicated
Expiry date: 01 September 2003
Specific Gravity: 0.969-0.976
Stability in vehicle
-Water: Not indicated
-Ethanol: Not indicated
-Acetone: Not indicated

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: Albino Rabbit, New Zealand White, (SPF-Quality) Recognised by international guidelines as the recommended test system (e.g. EC, OECD)
Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.

ANIMAL HUSBANDRY
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 16.1-23.0°C), a relative humidity of 30-70% (actual range: 43 -79%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually in labelled cages with perforated floors (Scan bur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,
Altromin, Lage, Germany) approx. 100 g per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Each animal was treated by dermal application of 0.5 ml of the test substance.

Duration of treatment / exposure:

4 hours.

Observation period:

72 hours.

Number of animals:

3 male rabbits

Details on study design:

TREATMENT
All available data relevant to the potential dermal irritation/corrosivity of the substance indicated that no severe effects were to be expected. An in-vitro skin irritation test was considered, but no validated test was found available. Therefore, this in-vivo skin irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Each animal was treated by dermal application of 0.5 ml of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

HISTOPATHOLOGY
No histopathology was performed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation: Four hours exposure to 0.5 ml of HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the three rabbits. The skin Irritation had resolved within 24 hours in two animals and within 48 hours in the other animal.
Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration: No staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.
Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

INDIVIDUAL SKIN IRRITATION SCORES

Following exposure, the treated skin-area remained fatty after removal of the test substance.

Animal#	442 (sentinel)			471			478
Time after exposure	Erythema	Oedema	Comments	Erythema	Oedema	Comments	Erythema	Oedema	Comments
1 hour	1	0	R b	1	0	R b	1	0	R b
24 hours	0	0	-	0	0	-	0	1	-
48 hours	0	0	-	0	0	-	0	0	-
72 hours	0	0	-	0	0	-	0	0	-

Comments: R. Erythema at the edges of the application-area; b. Sticky remnants of the test substance present at the edges of the application-area.

 

MEAN VALUE IRRITATION SCORES

Animal#	Mean 24-72 hrs
	Erythema	Oedema
442	0.0	0.0
471	0.0	0.0
478	0.0	0.3

 

#Animal specification:

Animal no	Sex	Age at start (weeks)	Bodyweights (grams)
			Prior to application	At termination
442	Male	8-10	1845	1976
471	Male	7-9	1660	1805
478	Male	7-9	1562	1705

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Not irritating.

Executive summary:

Primary skin irritation/corrosion study with HATCOL 3331 in the rabbit (4-hour semi-occlusive application).

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B4, "Acute Toxicity - Skin irritation", OECD No 404, "Acute Dermal Irritation/Corrosion", US EPA, OPPTS 870.2500, Acute Dermal Irritation and JMAFF, JapaneseTest Guidelines.

Three rabbits were exposed to 0.5 ml of HATCOL 3331, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.

Exposure to HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the rabbits, which had resolved within 24 hours in two animals and within48 hours in the other animal.

Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for skin irritation.