Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 February - 27 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Commission Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, Test Data for Registration of Agricultural Chemicals, Skin Irritation (2-1-4), 12 Nohsan No. 8147, Agricultural Production Bureau
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
EC Number:
813-120-0
Cas Number:
1262967-45-2
Molecular formula:
C21H36O8 C26H46O8 C31H56O8 C36H66O8 C41H76O8
IUPAC Name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
Test material form:
liquid
Specific details on test material used for the study:
RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark and under nitrogen.
- Stability under test conditions: Asumed stable.
- Solubility and stability of the test substance in the solvent/vehicle: Applied as supplied.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: N/A
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: N/A
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): Applied as supplied.

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable): N/A

OTHER SPECIFICS: No

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Stock supply
- Age at study initiation: 32-33 weeks
- Weight at study initiation: 3.81-4.82 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): Each rabbit was offered 125 g of a standard laboratory rabbit diet per day.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 7-8 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 20 ºC
- Humidity (%): 40-70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12:12 light:dark

IN-LIFE DATES: From: 16 February 2012 To: 06 March 2012

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Applied as supplied (i.e. not diluted)

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): Untreated
- Concentration (if solution): N/A

POSITIVE CONTROL
- Amount(s) applied (volume or weight): Not conducted
- Concentration (if solution): N/A
Duration of treatment / exposure:
Prelim: 3 x 3 mins, 1 hour and 4 hour
Main test: 4 hours
Observation period:
72 hours
Number of animals:
Prelim: 1
Main test: 2
Details on study design:
TEST SITE
- Area of exposure: 25x25 mm
- % coverage: Not reported
- Type of wrap if used: Cotton wool and a Tubigrip elasticated bandage (for 1 h and 4 h exposures)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: Prelim test: 3 mins, 1 h and 4 h. Main test: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and approximately 1, 24, 48 and 72 hours later.

SCORING SYSTEM:
- Method of calculation:

Erythema and eschar formation:
No erythema :0
Very slight erythema (barely perceptible) :1
Well-defined erythema :2
Moderate to severe erythema :3
Severe erythema (beef redness) or eschar formation (injuries in depth) preventing grading of erythema ;4

Oedema formation:
No oedema ;0
Very slight oedema (barely perceptible) ;1
Slight oedema (edges of area well-defined by definite raising) ;2
Moderate oedema (raised approximately 1 millimetre) ;3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) :4

A primary irritation index (PII) was calculated from the erythema and oedema scores according to the following formula as described in Technical Report No. 66 “Skin irritation and Corrosion: Reference chemicals data bank” (March 1995) ECETOC, Brussels.

PII = ((Sum of erythema at 24/48/72 h) + (Sum of Oedema at 24/48/72 h)) / (3 • No. of animals)

The maximum possible score was 8.0. The PII was then used to classify the test substance.



Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Other effects:
- Other adverse local effects: None
- Other adverse systemic effects: None.

Any other information on results incl. tables

Table 1       Mean values for erythema and oedema (24/48/72 h after removal of dressing)

 

Animal no. / Sex

Erythema

Oedema

Test

Control

Test

Control

101 / female

0

0

0

0

185 / female

0

0

0

0

186 / female

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The Primary Irritation Index was calculated to be 0.0. According to the criteria of European Commission regulation 1272/2008, Tetraesters of pentaerythritol with 2- methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid did not require any classification and labelling.
Executive summary:

OECD 404 (2012) - In a primary dermal irritation study (OECD 404), young adult New Zealand White rabbits (3 females) were dermally exposed to 0.5 mL of undiluted Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid for 4 hours at an area measuring 25x25 mm.  Animals then were observed for 3 days.  Irritation was scored by the primary irritation index (PII) formula, as reported in Technical Report No. 66 “Skin Irritation and Corrosion: Reference Chemicals Data Bank” (March 1995), ECETOC, Brussels.

 

There was no sign of toxicity or ill health in any rabbit during the observation period. The mean Primary Irritation Index through the 24/48/72 h observation period was 0 (maximum value observed during the test was also 0).  In this study,  Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid was not a dermal irritant.

 

According to the criteria of European Commission Regulation 1272/2008, Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid does not require any classification or labelling with regards to skin irritation.