Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation/ corrosion: Not irritating; OECD 404; Rees, P. (2012)

Skin irritation: Not irritating; OECD 439; Hubbard, J. (2011)

Eye irritation: Not irritating; OECD 405; Rees, P. (2012)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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.
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)
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
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
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.



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.

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

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.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 August - 01 November 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
22 July 2010
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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 system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: Skin constructs supplied by SkinEthic Laboratories, Lyon, France
Details on animal used as source of test system:
N/A
Justification for test system used:
Guideline specific test system
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN three dimensional human skin model
- Tissue batch number(s):
- Production date: 30 August 2011
- Shipping date: 30 August 201
- Delivery date: 30 August 201
- Date of initiation of testing: 30 August 201

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 2 ºC
- Temperature of post-treatment incubation (if applicable): 37 ºC

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 25 mL PBS
- Observable damage in the tissue due to washing: No
- Modifications to validated SOP: No

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 h ± 5 mins
- Spectrophotometer: Not reported
- Wavelength: 540 nm
- Filter: Not reported
- Filter bandwidth: Not reported
- Linear OD range of spectrophotometer: Not reported

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Acceptable,ion CoA
- Barrier function: Acceptable,ion CoA
- Morphology: Acceptable,ion CoA
- Contamination: Acceptable,ion CoA
- Reproducibility: Acceptable,ion CoA

NUMBER OF REPLICATE TISSUES: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the viability after 3 minutes exposure is ≤ 50 %
- The test substance is considered to be non-irritant to skin if the viability after 3 minutes exposure is > 50 %.
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431 and 439: N/A
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): Undiluted

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): 10 µL
- Concentration (if solution): N/A

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL
- Concentration (if solution): 5 %
Duration of treatment / exposure:
3 mins
Duration of post-treatment incubation (if applicable):
Post exposure and rinsing the tissues were placed on the appropriate medium and incubated for 42 ±1 hour.

Upon completion of the recovery period, each tissue was rinsed with PBS before being placed on 2 mL of 0.3 mg/mL MTT in PBS and incubated for three hours at 37 ºC.

Following MTT immersion, the samples were extracted in acidified isopropanol (0.04 N HCl solution concentration) for 69 hours.
Number of replicates:
3
Species:
other: N/A
Strain:
other: N/A
Details on test animals or test system and environmental conditions:
N/A
Type of coverage:
other: N/A
Preparation of test site:
other: N/A
Vehicle:
other: N/A
Amount / concentration applied:
N/A
Duration of treatment / exposure:
N/A
Observation period:
N/A
Number of animals:
N/A
Details on study design:
N/A
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Mean of 3 replicates
Value:
0.78
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: No
- Direct-MTT reduction: No
- Colour interference with MTT: No

DEMONSTRATION OF TECHNICAL PROFICIENCY: Yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes
- Acceptance criteria met for variability between replicate measurements: Yes
- Range of historical values if different from the ones specified in the test guideline: N/A

Table 1       EPISKIN results

 

Sample

Tissue viability as % of mean OD of the negative control

Rep

Mean ± SD

A

B

C

Negative control

92.5

106.0

101.6

100.0 ± 6.9

Positive control

18.1

75.1

27.3

22.7 ± 6.5*

Test Item

110.4

89.6

101.9

100.6 ± 10.4

* mean calculated using replicates A and C as the result for replicate B was considered anomalous

 

Interpretation of results:
GHS criteria not met
Conclusions:
With a mean tissue viability of 100.6 ± 10.4 %, Reaction product of 3,5,5-trimethyl-hexanoic acid and 2-metheylpropanoic acid and pentaerythritol is considered to be non-irritant.
Executive summary:

OECD 439 (2011) - The skin irritation potential of Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid was assessed using an EpiSkin Reconstructed Human Epidermis (RHE) Model Kit in accordance with OECD Guidance 439 and GLP.

 

Triplicate tissues were exposed to the test item for 3 minutes. At the end of the exposure period the test item was rinsed and the tissues incubated for a further 42 h in the presence of maintenance solution which would be used for possible inflammatory mediator determination. Each tissue was then loaded with MTT for 3 h and any resultant colour extracted. After incubation and extraction with acidified isopropanol, the solutions were aliquoted for absorbance measurements. Absorbency at 570 nm of each well was measured using a spectrophotometer.

 

Mean viability of tissues exposed to the test substance after 3 minutes were 100.6 ± 10.4 %. It was considered unnecessary to perform IL-1a analysis as the results of the MTT test were unequivocal. The quality criteria required for acceptance of the results was met.

 

Under the conditions of this study the test substance is considered to be non-irritant to the skin and does not meet the criteria for classification according to European Commission Regulation 1272/2008.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 March - 27 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted in accordance with International guidelines and GLP. All guideline validity criteria were met.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye 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 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Stock supply
- Age at study initiation: 3.38-4.48 kg
- Weight at study initiation: 35-37 weeks
- Housing: Each animal was housed individually in a plastic cage with perforated floors.
- Diet (e.g. ad libitum): 125 g of a standard laboratory rabbit diet per day.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 10 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: 11 March 2012 To: 23 March 2012
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): Undiluted

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
Duration of treatment / exposure:
Test item not washed from eye
Observation period (in vivo):
72 h
Duration of post- treatment incubation (in vitro):
N/A
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not conducted
- Time after start of exposure: N/A

SCORING SYSTEM: Kay and Calandra (1962)
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
6
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: N/A
Remarks on result:
no indication of irritation
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.

Injection of the conjunctival blood vessels and moderate discharge were apparent in all treated eyes one hour after instillation. Conjunctival injection persisted in one case until the 48 hour assessment. The treated eyes of two animals were overtly normal 24 hours after instillation and the third animal was overtly normal 48 hours later.

Instillation of the test material gave rise to practically no initial pain response.

Table 1       Mean irritation scores after instillation of Tetraesters of pentaerythritol with 2- methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid

 

Area of eye

1 h

24 h

48 h

72 h

Cornea

0.0

0.0

0.0

0.0

Iritis

0.0

0.0

0.0

0.0

Conjunctiva

6.0

0.7

0.7

0.0

Total mean score

6.0

0.7

0.7

0.0

Interpretation of results:
GHS criteria not met
Conclusions:
The highest total mean score was 6.0 occurring at the one-hour observation; accordingly under the criteria Kay and Calandra (1962) Reaction product of 3,5,5-trimethyl-hexanoic acid and 2-metheylpropanoic acid and pentaerythritol was classified as “minimally irritating” to the eye. Tetraesters of pentaerythritol with 2- methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid does not require labelling in accordance with European Commission Regulation 1272/2008.
Executive summary:

OECD 405 (2012) - In a primary eye irritation study (OECD 405), undiluted Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid was instilled into the conjunctival sac of the right eye of three female New Zealand White rabbits. The left eye was left untreated. Neither eye was washed during the course of the test. Animals were then observed at 1, 24, 48 and 72 hours. Irritation was scored by the method of Kay and Calandra (1962).

 

There was no sign of toxicity or ill health in any rabbit during the observation period. Injection of the conjunctival blood vessels and moderate discharge were apparent in all treated eyes one hour after instillation. Conjuctival injection persisted in one case until the 48 h assessment. The treated eyes of two animals were overtly normal 24 h after instillation and the third animal was overtly normal 48 h later. Instillation of the test item gave rise to practically no initial pain response.

 

The highest mean score was 6.0, occurring at the 1 h observation (for conjunctiva). This was fully reversed by the 72 h timepoint in all animals.

 

Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid does not require classification or labelling in accordance with EC Commission Regulation (No.) 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation/ Corrosion

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.

OECD 439 (2011) - The skin irritation potential of Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid was assessed using an EpiSkin Reconstructed Human Epidermis (RHE) Model Kit in accordance with OECD Guidance 439 and GLP.

 

Triplicate tissues were exposed to the test item for 3 minutes. At the end of the exposure period the test item was rinsed and the tissues incubated for a further 42 h in the presence of maintenance solution which would be used for possible inflammatory mediator determination. Each tissue was then loaded with MTT for 3 h and any resultant colour extracted. After incubation and extraction with acidified isopropanol, the solutions were aliquoted for absorbance measurements. Absorbency at 570 nm of each well was measured using a spectrophotometer.

 

Mean viability of tissues exposed to the test substance after 3 minutes were 100.6 ± 10.4 %. It was considered unnecessary to perform IL-1a analysis as the results of the MTT test were unequivocal. The quality criteria required for acceptance of the results was met.

Eye Irritation (in vivo)

OECD 405 (2012) - In a primary eye irritation study (OECD 405), undiluted Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid was instilled into the conjunctival sac of the right eye of three female New Zealnd White rabbits. The left eye was left untreated. Neither eye was washed during the course of the test. Animals were then observed at 1, 24, 48 and 72 hours. Irritation was scored by the method of Kay and Calandra (1962).

 

There was no sign of toxicity or ill health in any rabbit during the observation period. Injection of the conjunctival blood vessels and moderate discharge were apparent in all treated eyes one hour after instillation. Conjuctival injection persisted in one case until the 48 h assessment. The treated eyes of two animals were overtly normal 24 h after instillation and the third animal was overtly normal 48 h later. Instillation of the test item gave rise to practically no initial pain response.

 

The highest mean score was 6.0, occurring at the 1 h observation (for conjunctiva). This was fully reversed by the 72 h timepoint in all animals.

 

Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid does not require classification or labelling in accordance with EC Commission Regulation (No.) 1272/2008.

Eye Irritation (in vitro)

Waiver - An vivo test which produced adequate results was conducted prior to entry into force of the amendments to Annexes VII and VIII. In this instance an in vitro test is not required.

Justification for classification or non-classification

The substance does not meet the criteria for classification in accordance with Regulation (EC) No 1272/2008 (CLP).