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Administrative data

Description of key information

For the endpoint skin irritation/corrosion there is an in vitro study available (Andres, 2013) indicative of the fact that the substance is a non-corrosive substance. In addition there is an acute dermal toxicity study (Salvador, 2014) from which there were no indications of skin irritating effects. Based on these studies the substance can be regarded as non-irritating to the skin. 
With regard to the eye irritation effects, there are also two studies available. Both the in vitro (Andres, 2013) and the in vivo study (Salvador, 2014) indicate that the test item, Trimethylolpropane Tripelargonate, has no eye irritating properties.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been conducted in according to OECD guideline and GLP without deviation
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: B.40 BIS (In vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
human
Strain:
other: Commercially available Epi-200-Kit.
Details on test animals or test system and environmental conditions:
Epi-200 tissues were procured from MatTek In Vitro Life Science Laboratories.
Day of delivery: 08. Oct. 2013
Batch EPI-200-CORR: 18381

Chemicals and Media:
- MTT reagent: Contains 1mg/mL 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, which can be reduced to a blue formazan. Prepared as concentrate (5mg/mL in DPBS buffer, stored at -20 °C).
For the pre-test, the concentration was thawed and diluted with serum-free MEM medium directly before use.
For the main study, the concentrate was thawed and diluted with assay medium directly before use.

Isopropanol 99,9%, batch 3100602 used as exctracting solvent for formazan


Details on study design:
The EpiDerm tissu consists of normal, human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epiderms. It consists of organised basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo. The EpiDerm tissues are cultured on specially prepared cell cultures inserts. Negative control: Deionised H2O Positive control: KOH, solution in deionised H2O containing 8.0 mol/L
Irritation / corrosion parameter:
dye content (µg/disc)
Value:
ca. 98.1
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

Assessment:

 % Formazan productionafter 3 min. incubation time % Formazan productionafter 1 h incubation time  Assessment 
 < 50% of negative control  irrelevant  Corrosive!
 > = 50% of negative control  < 15% of negative control  Corrosive!
 >= 50% of negative control  >= 15% of negative control  not corrosive

Results:

The absorption values of negative control, test item and positive control are given in the following table:

Negative Control   Test Item  Positive Control  Incubation time
Tissue 1  Tissue 2  Tissue 1  Tissue 2  Tissue 1  Tissue 2     
 2.202  1.956  2.067  2.075  0.443  0.472     3 min
 2.199  1.975  2.048  2.026  0.452  0.465     3 min
 2.166  2.074  2.038  2.079  0.452  0.459  3 min   
 1.948  2.014  1.716  1.875  0.199  0.205     1 hour
 1.986  1.924  1.750  1.916  0.198  0.203     1 hour
 1.986  2.016  1.756  1.909  0.194  0.204     1 hour
 Mean  Mean  Mean  
 2.095  2.056  0.457  3 min
 1.979  1.820  0.201  1 hour

Validity:

The criterion for optical density of the negative control (> 0.8) was fulfilled: optical density was 2.095 (3 minutes) resp. 1.979 (1 hour). The positive control showed a clear corrosive effect: the value of the three-minuteexperiment was 21.8 % and the value of the one-hour-experiment was 10.1 %. Values for negative control and for positive control were within the range of historical data of the test facility (see Annex 2: Comparison with Historical Data, page 17). Therefore, the experiment is considered valid.

Discussion:

The test item is considered not corrosive. After three minutes treatment, the relative absorbance values were decreased to 98.1 %. This value is well above the threshold for corrosivity (50 %). After one hour treatment relative absorbance values were reduced to 92.0 %. This value is well above the threshold for corrosivity (15 %). In the guideline, values greater or equal to the threshold are considered as “non-corrosive to skin”. The values of the negative control were well above the required acceptability criterion of mean OD > 0.8 for both treatment intervals thus showing the quality of the tissues. The positive control induced a decrease in the relative absorbance as compared to the negative control to 21.8 % for the three minutes treatment interval and 10.1 % for the one hour treatment interval thus ensuring the validity of the test system. For these reasons, the result of the test is considered valid.

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Trimetilolpropano tripelargonato is considered as "not corrosive in the human Skin Model Test"
Executive summary:

The study was followed in according to OECD guideline and GLP without significate deviations.

Two tissues of the human skin model EpiDermTM were treated with TRIMETILOLPROPANO TRIPELARGONATO for three minutes and one hour, respectively. 50 μL of the liquid test item were applied to each tissue and spread to match the tissue size. Deionised water was used as negative control, 8M KOH was used as positive control. After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT which can be reduced to a blue formazan. Formazan production was measured by measuring the optical density (OD) of the resulting solution. After treatment with the negative control, the absorbance values were well above the required acceptability criterion of mean OD > 0.8 for both treatment intervals thus showing the quality of the tissues. The positive control showed clear corrosive effects for both treatment intervals. After three minutes treatment with the test item, the relative absorbance values were reduced to 98.1 %. This value is well above the threshold for corrosion potential (50 %). After one hour treatment, relative absorbance values were reduced to 92.0 %. This value, too, is well above the threshold for corrosion potential (15 %). In the guideline, values greater or equal to the threshold are considered as “non-corrosive to skin”.

In according to the OECD guideline 431, TRIMETILOLPROPANO TRIPELARGONATO is considered as “not corrosive in the Human Skin Model Test”.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recent well documented GLP study according to international guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: The eye of each animal treated with the anaesthetic but not with the test item served as control.
Duration of treatment / exposure:
Animals were dosed once only on the day of dosing (Day 1). Each animal was treated with 0.1 mL aliquot of the test item onto the right eye.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after the end of dosing.
Number of animals or in vitro replicates:
3 animals/group
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 h post-dose observation.
Score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 0 -72h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 0 - 72h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 0 - 72h
Score:
0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
These results indicate that the test item, Trimethylolpropane Tripelargonate, has no relevant irritating effect on the eye of the rabbit.
Executive summary:

The acute eye irritation of Trimethylolpropane Tripelargonate was investigated in rabbits. A 0.1 mL aliquot of the test item was introduced into the right eye of a total of 3 animals. The resulting reaction to treatment was assessed approximately 1, 24, 48, and 72 hours after dosing. No significant irritation at either the conjunctivae, iris or cornea was recorded in any treated animal during the study. There were no signs of pain/distress after dosing. Changes in body weight were not remarkable. There was no indication of a systemic effect related to treatment. These results indicate that the test item, Trimethylolpropane Tripelargonate, has no relevant effect on the eye of the rabbit.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
This in vitro skin corrosion study by Andres (2013) is a well documented, recent GLP study according to international guidelines. Moreoever, based on the acute dermal toxicity results reported in the study of Salvador (2014) (LD50 > 2000 mg/kg bw), no skin irritating properties are expected.

Justification for selection of eye irritation endpoint:
There are two studies available, one in vitro and one in vivo. The identified key study study is an in vivo eye irritation study in rabbits, which was performed according to GLP and international guidelines (Salvador, 2014).

Justification for classification or non-classification

Skin irritation:

As no skin irritating properties are expected based on the in vitro Human Skin Model Test following OECD guideline 431 results, and no skin irritation effects were seen in the acute dermal toxicity study, the substance is not to be classified according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of substance and mixtures (CLP) nor Directive 67/548/EEC (Dangerous Substances Directive).

Eye irritation

As no effects of eye irritation or eye damage are observed in any of the performed studies (OECD 437 and 405), the substance is not to be classified according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) nor Directive 67/548/EEC (Dangerous Substances Directive).