Registration Dossier

Administrative data

Description of key information

After repeated skin contact with Hydroxypropyl acrylate sensitization is possible.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Age at study initiation: 8 weeks
- Weight at study initiation: 17.0 - 21.0 g
- Housing: single housing (Polycarbonate cages type MII)
- Diet (e.g. ad libitum): Kliba mouse/rat maintenance diet “GLP”, supplied by Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum.
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: al least 5 days before the first application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
methyl ethyl ketone
Concentration:
1, 5 and 10% w/w
No. of animals per dose:
5
Details on study design:
The study comprised three treatment groups, a vehicle control group and a positive control group. Each group consisted of 5 mice. Epicutaneous application is simulating dermal contact with the compound which is possible to occur under practical use conditions. 25 µL per ear dorsal part of both ears. 3 consecutive application (day 0 – day 2) to the same application site. On study day five (about 66 to 72 hours after the last application of test substance to the ears) the mice were injected into a tail vein with 20 µCi of 3H-thymidine in 250 µL of sterile saline. The animals were sacrificed on study day 5 about 5 hours after 3H-thymidine injection by cervical dislocation under Isoflurane anesthesia. Immediately after the death of each animal a circular piece of tissue (diameter 0.8 cm) was punched out of the apical part of each ear of all animals. The weight of the pooled punches was determined for each animal. These measurements serve for detecting a potential inflammatory ear swelling. Immediately after removal of the ear punches the left and right auricular lymph nodes were dissected. The weight of the pooled lymph nodes from both sides was determined for each animal.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
3H-thymidine incorporation, cell count, lymph node weight and ear weight: WILCOXON - Test
Positive control results:
A concurrent positive control with Alpha-Hexylcinnamaldehyde was included in this study. Additionally, studies using the positive control substance Alpha-Hexylcinnamaldehyde are performed twice a year in the laboratory in order to show that the test system is able to detect sensitizing compounds under the test conditions chosen (reliability check).
Parameter:
EC3
Value:
3.1

³H-thymidine incorporation, cell count and lymph node weight:

When applied as a 5% or 10% preparation in MEK, the test substance induced astatisticallysignificant increase of3H-thymidine incorporation into the cells from the auricular lymph nodes, which was above the cut off value forbiological relevance(increase above the cut off stimulation index (SI) of 3). The stimulation indices are 4.39 and 8.57 at 5% and 10%, respectively. Concomitantly, the increases in the auricular lymph node cell counts at 5% (SI = 1.68) and 10% (SI = 2.01) werestatistically significant and biologically relevant (above the cut-off value(increase to 1.5 fold or above of control value = stimulation index (SI)≥1.5). In addition, statistically significant increases in lymph node weights at 5% (Si = 1.43) and 10% (SI = 1.79) were noted. No relevant increase in either of above endpoints were observed at 1% preparation. The 15% HCA preparation in MEK induced a biologically relevant and statistically significant response in3H-thymidine incorporation (SI = 7.99) and lymph node cell counts (SI = 2.24) as well as statistically significant increased lymph node weights (SI = 2.05).

Ear weights:

The ear weight stimulation indices did not indicate any signs of relevant increase (SI≤ 1.25).

Test group

Tretment

³H-tymidine incorporation Stimulatin Index1

Cell Count Stimulatin Index1

Lymph Node Weight Stimulation Index1

Ear Weight Stimulation Index1

1

vehicle MEK

1.00

1.00

1.00

1.00

2

1% in MEK

1.41

1.02

0.98

1.00

3

5% in MEK

4.39##

1.68##

1.43##

1.00

4

10% in MEK

8.57##

2.01##

1.79##

1.01

5

positive control HCA 15% in MEK

7.99##

2.24##

2.05##

1.10##

1test group x / test group 1 (vehicle control)

The statistical evaluations were performed using the Wilcoxon-test (# for p0.05, ## for p0.01)

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Thus, it is concluded that Hydroxypropylacrylate exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The skin sensitizing potential of Hydroxypropylacrylate was assessed using the radioactive Murine Local Lymph Node Assay. Groups of 5 female CBA/CaOlaHsd mice each were treated with 1%, 5% and 10% w/w preparations of the test substance in methyl ethyl ketone (MEK) or with the vehicle alone. The high concentration was selected based on the presence of ear skin irritation in a pretest using a 25% preparation. Concomitantly, the increases in the auricular lymph node cell counts at 5% and 10% were statistically significant and biologically relevant (above the cut-off value (increase to 1.5 fold or above of control value = stimulation index (SI)≥1.5). In addition, statistically significant increases in lymph node weights at 5% and 10% were noted. The testsubstance concentrations did not cause any increase in ear weights, demonstrating the absence of ear skin irritation. However, very slight erythema of the ear skin was observed in all animals treated with the 5% concentration on study day 2 and in all animals treated with the 10% concentration on study day 1 and 2. The 15% HCA preparation in MEK induced a biologically relevant and statistically significant response in3H-thymidine incorporation and lymph node cell counts as well as statistically significant increased lymph node and ear weights. In addition, very slight erythema and slight swelling were observed on the ear skin on study day 1 and 2. Thus, it is concluded that Hydroxypropylacrlate exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.

The threshold concentration for sensitization induction was >1% <5%. The EC 3 (estimated concentration that leads to the SI of 3.0) for3H-thymidine incorporation and the EC 1.5 (estimated concentration that leads to the SI of 1.5) for cell countwas calculated by linear regression from theresults of these concentrations to be 3.1% and 3.9%, respectively.

Hydroxypropyl acrylate and one of the components (2 -hydroxypropyl acrylate CAS 999 -61 -1) have been tested in several studies using guinea pigs with varying results.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information available on the potential for Hydroxypropyl acrylate to produce respiratory sensitisation in animals.

Justification for classification or non-classification

Based on the available data, the substance has to be classified for Skin Sens. cat. 1: H317: May cause an allergic skin reaction according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.