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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 November 2013 - 19 November 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
individual approach (adopted 22 July 2010)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
dated May 30, 2008
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

In vivo test system

Test animals

Species:
mouse
Strain:
other: Mice, CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- CBA/CaOlaHsd mice, nulliparous, non-pregnant
- Age at study initiation (pre-test and main study): 8 - 9 weeks (beginning of treatment)
- Weight at study initiation (main test): 18.0 g - 22.2 g
- Housing: single; Makrolon Type II (pre-test)/ III (main study, with wire mesh top
- Diet (e.g. ad libitum):2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days prior to start of dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 35-65 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
1 (Control ) 0
2 (Low Dose) 25% (w/v)
3 (Mid Dose) 50% (w/v)
4 (High Dose) 100% (w/v)
No. of animals per dose:
Main study: 5 females (nulliparous and non-pregnant)
Pre-test: 2 females
Details on study design:
RANGE FINDING TESTS:
Concentrations of 50 and 100 % of the test substance were tested on two mice on one ear each once daily each on three consecutive days. The animals were sacrificed on day 6.
In the pre-test the tested animals did not show any signs of systemic toxicity.
From day 3 up to day 6, the animal treated with 50% test item concentration showed an erythema of the ear skin (Score 1). On day 2, 3 and day 6 the animals treated with 100% of the test item showed an erythema of the ear skin (Score 1), and on day 4 and 5 an erythema of the ear skin (Score 2). In addition the ears were scabby on day 5 and 6. No excessive increase in ear weights and/or ear thickness values were observed.
Thus, the test item in the main study was assayed at 25, 50 and 100%. The highest concentration tested was the highest level that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation as confirmed in the pre-experiment.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables and for the DPM values (group mean DPM ± standard deviation).
The Dean-Dixon-Test and the Grubb's test were used for identification of possible outliers (performed with Microsoft Excel 2007).
However, both biological and statistical significance were considered together.

Results and discussion

Positive control results:
A positive control performed with alpha-Hexylcinnamaldehyd in October 2016 resulted in an S.I. of 1.5 at 5% (w/v)
alpha-Hexylcinnamaldehyd in acetone/olive oil (4+1, v/v), 3.84 at 10 % and 11.76 at 25 %. An EC3 of 8.2 % (w/v) was calculated.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
EC3
Value:
91.6
Parameter:
SI
Value:
1.4
Test group / Remarks:
25%
Parameter:
SI
Value:
1.51
Test group / Remarks:
50%
Parameter:
SI
Value:
3.3
Test group / Remarks:
100%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Vehicle control group (negative control with vehicle, only): 999.4 DPM per lymph node (2 lymph nodes) Test substance 25% DPM/lymph node: 1398.8 50% DPM/lymph node: 1510.2 100% DPM/lymph node: 3296.8

Any other information on results incl. tables

Calculation and Results of Individual Data

Vehicle: acetone/olive oil (4+1 v/v)

Test item concentration

DPM values measured

DPM-BG per animal
(2 lymph nodes)a)

S.I.b)

%

Group no.

Animal no.

---

---

BG I

24

---

---

---

---

BG II

24

---

---

0

1

1

482

458.0

---

0

1

2

927

903.0

---

0

1

3

1007

983.0

---

0

1

4

1106

1082.0

---

0

1

5

1595

1571.0

---

25

2

6

1925

1901.0

1.9

25

2

7

1563

1539.0

1.5

25

2

8

1710

1686.0

1.7

25

2

9

1116

1092.0

1.1

25

2

10

800

776 .0

0.8

50

3

11

760

736.0

0.7

50

3

12

1918

1894.0

1.9

50

3

13

1625

1601.0

1.6

50

3

14

1823

1799.0

1.8

50

3

15

1545

1521.0

1.5

100

4

16

3100

3076.0

3.1

100

4

17

5249

5225.0

5.2

100

4

18

2036

2012.0

2.0

100

4

19

3746

3722.0

3.7

100

4

20

2473

2449.0

2.5

1    =  Control Group

2-4=  Test Group

a)   =  values corrected for mean background value (BGI and BGII)

b)    =  Stimulation Indices relative to the mean of the control group (Group 1)

Applicant's summary and conclusion

Interpretation of results:
sensitising
Conclusions:
In this vaild Local Lymph Node Assay according to OECD 429 Triethyleneglycol dimethacrylate is a dermal sensitiser.
CLP EU GHS (Regulation (EC) No 1272/2008) classification: sensitizing category 1B (EC3 value > 2%)
Executive summary:

In this vaild dermal sensitisation study according to OECD Guideline 429 (adopted July 2010) Triethyleneglycol dimethacrylate (purity: 99.68%) in acetone:olive oil (4+1, v/v), groups of 5 female CBA/CaOlaHsd mice were tested using the LLNA method with the individual approach.

In this Local Lymph Node Assay Triethyleneglycol dimethacrylate is a dermal sensitiser.

 

No systemic findings were observed during the study period. Only the highest dose (100%) induced slight erythema on the ear skin on days 3 to 6 (Score 1). Animals treated with 25 and 50% of the test item did not show any signs of local skin irritation.

The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age. No cases of mortality were observed.

STIMULATION INDICES (S.I.) of 1.40, 1.51 and 3.30 were determined with the test substance at concentrations of 25%, 50% and 100% (w/v) in acetone:olive oil (4+1, v/v), respectively. The positive control substance was α-Hexylcinnamaldehyde, which gave an EC3 at 9.3 % (w/v). A result is regarded as positive when the S.I. is ≥3.

Based on these criteria, the test substance was found to be a sensitiser. The EC3 was calculated to be 91.6 %.

In this study, Triethyleneglycol dimethacrylate is a dermal sensitiser.

CLP EU GHS (Regulation (EC) No 1272/2008) classification: sensitizing category 1B (EC3 value > 2%)

 

 

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