Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

There are valid study data available to assess the sensitising potential ethoxylated trimethylolpropane triacrylate (TMPeoTA).

Guideline conform studies:

TMPeoTA was tested for its sensitizing effect on the skin of the guinea pig in the BUEHLER Test based on the method of BUEHLER, E .V. (1965) according to OECD 406 (BASF, 2004, Gamer A.O.). The test substance concentrations for the main test were selected based on the results of the pretest. All inductions were performed with the undiluted test substance, for the 1 st challenge a 75% and for the 2 nd challenge a 50% test substance preparation in doubly distilled water was chosen. The study was performed using 1 control group and 1 test group. The inductions were performed on days 0, 7 and 14 . Two challenges were carried out 14 and 21 days after the last induction. The first until third induction caused discrete or patchy to intense erythema and swelling in the test group animals . After the 1 st challenge discrete or patchy to moderate and confluent erythema and swelling could be observed in the test group animals . Due to discrete or patchy erythema observed in two control group animals the test substance concentration was reduced for the 2 nd challenge. The 2nd challenge caused discrete or patchy to moderate and confluent erythema in test group animals only. The number of animals with skin findings after the 1 st challenge and 2nd challenge is summarized in the following table: Control group: 1 st challenge 2/10; Test group: 1 st challenge 9/20, Control group: 2 nt challenge 0/10; Test group: 2 nd challenge 9/20. Based on the results of this study it was concluded that "confidential substance name" has a sensitizing effect on the skin of the guinea pig in the BUEHLER Test under the test conditions chosen.

In another test the skin sensitizing potential of TMPeoTA was assessed using the non-radioactive variant of the Murine Local Lymph Node Assay (BASF, 2006, Gamer A. O.). Groups of 6 female CBA/Ca mice each were treated with 3%, 10% and 30% w/w preparations of the test substance in acetone or with the vehicle alone . The study used 3 test groups and 2 control groups. Each test animal was applied with 25 µL per ear of the respective test-substance preparation to the dorsum of both ears for three consecutive days .One control group was treated with 25 µL per ear of the vehicle alone, the other control group remained untreated to serve as a control for the immunological status of the animals. Three days after the last application the mice were sacrificed and the auricular lymph nodes were removed. Lymph node response was evaluated by measuring the cellular content (indicator of cell proliferation) and weight of each animal's pooled lymph nodes. Moreover, a defined area with a diameter of 0.8 cm was punched out of the apical part of each ear and for each animal the weight of the pooled punches was determined in order to obtain an indication of possible skin irritation. No signs of systemic toxicity were noticed . The test substance induced a statistically significant and biologically relevant response of the auricular lymph nodes when applied as 3%, 10% and 30% preparations in acetone. The statistically significant increased ear weights and additional clinical signs of skin irritation (eczematoid skin changes in 4 animals applied with the 10% preparation and in all animals of the 30% test group) indicate the induction of slight to moderate ear skin irritation by these concentrations. Taking into account the strong lymph node response, however, even in the low concentration with only weak ear skin irritation, the test substance is considered to be a skin sensitizer. In conclusion, the test substance has a skin sensitizing effect in the Murine Local Lymph Node Assay. The threshold concentration for sensitization induction was < 3% under the test conditions chosen.

A further murine local lymphode assay with another batch of TMPeoTA was performed equivalent to OECD 429 (BASF, 2002, Gamer A.O. (a)). This sensitisation test was performed in two steps . In the first step concentrations of 3, 10 and 30% of the test substance in acetone were used. As lymph node reactions were produced by all concentrations, in the second step concentrations of 1, 0.3 and 0.1% were examined in order to determine a concentration not inducing lymph node reactions. Groups of 6 female CBA/Ca mice each were treated with several concentrations of preparations of the test substance in acetone or with the vehicle alone . Each step of the study used 3 test groups and 2 control groups. Each test animal was applied with 25 µL per ear of the respective test substance preparation to the dorsum of both ears for three consecutive days. No signs of systemic toxicity were noticed. A statistically significant increase in lymph node cellularity and in lymph node weights was induced by test substance concentrations of 3% and above. Based on the results of the study it is concluded, that under the test conditions chosen the test substance does have a sensitizing effect in the murine Local Lymph Node Assay. The maximum concentration which did not produce lymph node responses and thus is considered to represent the no effect concentration for sensitization induction in this test model is 1%.

Another test was performed to assess the sensitising potential of TMPeoTA (BASF, 2002, Gamer A.O. (b)). Therefore groups of 6 female CBA/Ca mice each were treated with 3, 10 and 30% of the test substance diluted in acetone or with the vehicle alone. The study used 3 test groups and 2 control groups and was conducted equivalent to OECD guideline. Each test animal was applied with 25 µL per ear of the respective test substance preparation to the dorsum of both ears for three consecutive days. No signs of systemic toxicity were noticed. A statistically significant increase in lymph node cellularity and in lymph node weights was observed in animals treated with test substance concentrations of 3, 10 and 30%. The increased ear weights and clinical signs of skin irritation (eczematoid skin changes in 4 animals, applied with the 10% preparation and in all animals of the 30% test group) indicated a significant irritant property of the test substance when applied in these concentrations. Taking into account the strong lymph node response, however, even in the lowest concentration with only moderate ear skin irritation, the test substance is considered to be a skin sensitizer. From the results of the study no threshold concentration for sensitization induction can be derived.

Another sensitisation test equivalent to OECD 429 was performed in two steps (BASF, 2004, Gamer A.O. (d)).0.1% 0.3%, 1%, 3%, 10% and 30% test substance in acetone were used to determine a concentration not inducing lymph node reactions. Groups of 6 female CBA/Ca mice each were treated with several concentrations of preparations of the test substance in acetone or with the vehicle alone. No signs of systemic toxicity were noticed. The test substance induced a statistically significant and biologically relevant proliferation of the auricular lymph nodes and cell counts when applied as 1%, 3% or 10% test substance preparation in acetone. A statistically significant increase in lymph node cellulariy but not in Lymph node weight was observed for 0.3% test substance concentration. The threshold concentration for sensitization induction was > 0.3% < 1% under the test conditions chosen. Due to the applicant this study was only less documented and is there only used as underlining information and not take into account for assessment.

Tests according to other guidelines:

A Local Lymphnode Assay was conducted to assess the sensitising potential of TMPeoTA (BASF, 2004, Gamer A.O. (c)). Therefore 6 mice per dose group received 25µL 3% test substance in acetone (or pure acetone; control group) during the induction phase and 14 days later 1% during the challenge phase dermally applied to the ear. The Test substance induced a statistically significant increase of lymph node cellularity and lymp node weights in both the induction and the challenge phase compare to the control. Based on the results of the study it was concluded, that under the test conditions chosen the test substance has a sensitizing effect in the murine Local Lymph Node Assay. Due to the applicant this study was only less documented and is there only used as underlining information and not take into account for assessment.

 

Assessment sensitisation:

All available information is taken into account to assess the sensitising potential ethoxylated trimethylolpropane triacrylate (TMPeoTA). Due to the less documentation (short detailed summary) of four BASF studies ( (BASF, 2004, Gamer A.O. (a-d) these studies are rated lower for assessment. Nevertheless the results obtained from these four studies confirmed the result of the more reliable documented studies from BASF (BASF, 2004, Gamer A.O. and BASF, 2006, Gamer A. O.).

All available studies showed sensitising effects for TMPeoTA and one study derives a threshold of 1 % (NOEC), whereas most other conducted studies were performed with much higher concentration. In result TMPeoTA is a skin sensitizer, with a possible threshold below 3% (based on the result of non radioactive LLNA with good documentation).

Key study assignment:

Due to the less documentation of four BASF studies (BASF, 2004, Gamer A.O. (a-d) these studies are rated as less reliable than the other available studies. All remaining available studies are equal in quality. Both studies are conducted according to OECD guideline (BASF, 2004, Gamer A.O. and BASF, 2006, Gamer A. O.)) and showed both sensitizing effects, but the LLNA test was done non radioactive which is a method under debate. Therefore the Buehler test is chosen as key study (BASF, 2004, Gamer A.O.) as it represents the most reliable and relevant study. Nevertheless all other studies were entered as supporting studies.


Migrated from Short description of key information:
Buehler test, guinea-pig, OECD 406: sensitising, 9/20 positive (@50%) (BASF, 2004, Gamer A.O.)
LLNA, mice, non radioactive, OECD 429: sensitising; threshold < 3% (BASF, 2006, Gamer A. O.)

Respiratory sensitisation

Endpoint conclusion
Additional information:

No valid information for TMPeoTA on respiratory sensitisation is available.


Migrated from Short description of key information:
No data available

Justification for classification or non-classification

Skin sensitisation:

According to GHS and DSD substances shall be classified as skin sensitiser if there are positive results from appropriate animal test. A Buehler test shows positive findings for 9/20 tested animals (well more than 15%) showing the sensitising potential of the test substance. This is also underlined by different positive mouse local lymphnode assays. Hence the substance needs to be classified according to GHS (Regulation (EU) 1272/2008) as sensitising to skin and also needs to be classified according to DPD (67/548/EEC) Xi R-43.

 

Labelling for skin sensitisation:

GHS: sensitising to skin

DSD: Xi R-43

 

Respiratory sensitisation:

No labelling can be derived due to leak of information

 

Respiratory sensitisation:

No labelling can be derived due to leak of information