Reaction mass of 2-hydroxy-1,3-propanediyl bismethacrylate and 101525-90-0

Endpoint summary

Description of key information

LLNA (OECD 429, GLP): not sensitizing (Envigo 2017)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.08.2016 - 21.12.2016

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

adopted 22. July 2010

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

Batch No. : 20104-24D
Reactiveester content: 96.07 %
Diester content (isomer mix): 86.4%
Triester content. 1.9 %
Methacrylic acid: 0.86%
Expiry Date: 15 January 2017
Storage Conditions: At room temperature

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): 9 - 10 weeks (beginning of treatment)
- Weight at study initiation (main test): 17.8 - 21.1 g
- Housing: single; Makrolon Type II (pre-test)/ III (main study, with wire mesh top
- Bedding: granulated soft wood bedding
- 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 (%): 45-65% (except for deviations)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

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

Concentration:

1 (Control ) 0
2 (Low Dose) 0.5 % (w/v)
3 (Mid Dose) 2.5 % (w/v)
4 (High Dose) 5 % (w/v)

No. of animals per dose:

Main study: 5 females (nulliparous and non-pregnant)
3 Pre-tests: 2 females (each)

Details on study design:

To determine the highest non-irritant test concentration that at the same time did not induce signs of systemic toxicity, a pre-test was performed in two animals and stated in raw data and report. Two mice were treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 50 and 100% once daily each on three consecutive days. Prior to the first application of the test item and before sacrifice the body weight was determined. Clinical signs were recorded at least once daily. Eventual signs of local irritation were documented and a score was used to grade a possible erythema of the ear skin. Furthermore, prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6) the ear thickness was determined using a micrometer. Additionally, for both animals, the ears were punched after sacrifice (day 6) at the apical area using a biopsy punch (Ø 8 mm corresponding to 0.5 cm2) and were immediately pooled per animal and weighed using an analytical balance. Eventual ear irritation was considered to be excessive if an erythema of the ear skin of a score value ≥3 was observed at any observation time and/or if an increase in ear thickness of ≥25% was recorded on day 3 or day 6.
At the tested concentrations the animals showed an erythema of the ear skin (Score 3) and a decrase of body weight >5% from day 1 to day 3. Furthermore, the animal treated with 50% of the test item showed beginning eschar formation.
Therefore, the animals were sacrificed and a second pre-test performed with concentration of 10 and 25% was performed. At these concenrations, the animals showed an erythema of the ear skin (Score 1 to 2), slight erythema of scalp and slight eschar formation.The animal treated with 25% of the test item showed visible swelling of the ears and a transient decrease in body weight. Furthermore, for the animal treated with 25%, an increase of ear thickness and ear weight above the recommended threshold was also observed.
Therefore, a third pre-test was performed using concentrations of 2.5 and 5%. Both animals showed an erythema of the ear skin (Score 1 to 2) as well as scaly ears and slight eschar formation on day 6. Additionally, the animal treated with 5% test item concentration showed slight erythema of the scalp and increased spontaneous activity.
Despite the signs of irritation observed in the pre-test, the main study was performed at test item concentrations of 0.5, 1, 2.5, and 5 to cover as far as possible the concentration range in which the substance is used in practice.


MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response:

TREATMENT PREPARATION AND ADMINISTRATION:

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Within the program the Dean-Dixon-Test and Grubb’s Test were used for identification of possible outliers. An outlier (DPM value determined for animal 8) was detected in the Dean Dixon Test, but not in the Grubb’s Test, and was therefore not excluded from calculations.

Positive control results:

A positive control performed with alpha-Hexylcinnamaldehyd in October 2013 resulted in an S.I. of 1.8 at 5% (w/v)
alpha-Hexylcinnamaldehyd in acetone/olive oil (4+1, v/v), 3.2 at 10 % and 5.8 at 25 %. An EC3 of 9.3 % (w/v) was calculated.

Parameter:

SI

Value:

1

Test group / Remarks:

Vehicle control

Parameter:

SI

Value:

1.1

Test group / Remarks:

0.5 % Glycerol dimethacrylate

Parameter:

SI

Value:

1.1

Test group / Remarks:

1.0 % Glycerol dimethacrylate

Parameter:

SI

Value:

1

Test group / Remarks:

2.5 % Glycerol dimethacrylate

Parameter:

SI

Value:

0.7

Test group / Remarks:

5 % Glycerol dimethacrylate

Calculation of Stimulation Indices per Dose Group

Test item concentration	Group calculation
	Mean DPM per animal (2 lymph nodes)a)	SD	S.I.
Vehicle Control Group (acetone/olive oil (4+1, v/v))	2554.1	1263.1	1.0
0.5% Glycerol dimethacrylate	2808.5	1558.9	1.1
1% Glycerol dimethacrylate	2705.7	964.5	1.1
2.5% Glycerol dimethacrylate	2618.7	1672.6	1.0
5% Glycerol dimethacrylate	1913.1	284.6	0.7

Interpretation of results:

GHS criteria not met

Conclusions:

In this vaild Local Lymph Node Assay according to OECD 429 Glycerol dimethacrylate was not a skin sensitizer.
CLP EU GHS (Regulation (EC) No 1272/2008) classification: not sensitizing

Executive summary:

In this vaild dermal sensitisation study according to OECD Guideline 429 (adopted July 2010) Glycerol dimethacrylate 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 Glycerol dimethcrylate was not a sensitizer.

 

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. From day 2 to 6 the animals treated with test item concentrations of 2.5 and 5% showed an erythema of the ear skin (Score 1), as well as scaly ears on test days 5 and 6. Animals treated with 0.5 and 1% test item concentrations did not show any signs of local skin irritation. In this study Stimulation Indices (S.I.) of 1.1, 1.1, 1.0, and 0.7 were determined with the test item at concentrations of 0.5, 1, 2.5, and 5% in acetone/olive oil (4+1, v/v), respectively.

CLP EU GHS (Regulation (EC) No 1272/2008) classification: not sensitizing

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In this vaild dermal sensitisation study according to OECD Guideline 429 (adopted July 2010) GDMA 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.

 

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. From day 2 to 6 the animals treated with test item concentrations of 2.5 and 5% showed an erythema of the ear skin (Score 1), as well as scaly ears on test days 5 and 6. Animals treated with 0.5 and 1% test item concentrations did not show any signs of local skin irritation. In this study Stimulation Indices (S.I.) of 1.1, 1.1, 1.0, and 0.7 were determined with the test item at concentrations of 0.5, 1, 2.5, and 5% in acetone/olive oil (4+1, v/v), respectively.

In this Local Lymph Node Assay GDMA was not a sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on a reliable LLNA assay, GDMA is classified as not skin sensitizing according to Annex I of CLP/EU-GHS (1272/2008/EC) and UN-GHS.