Registration Dossier

Administrative data

Description of key information

The substance was considered to be sensitising to the skin.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Well documented publication, acceptable for assessment with restrictions (limited information on material and methods, no derivation of an EC3 possible based on available data, corrosive substance). Due to the corrosive properties of the substance, all experimental data on skin sensitization are of restricted reliability, since local irritating effects can interfere with effects caused by skin sensitization.
Principles of method if other than guideline:
The study was conducted according to the method described by Kimber et al. (1989, 1991) and Basketter et al. (1991) with one modification. In the study described here animals received topical applications of test chemical on three consecutive days and the assay was terminated after 5 days.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-Hydroxyethyl acrylate
- Analytical purity: >= 98 % (purity refers to majority of used test chemicals, no specifics given)
- Source: Fluka
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CBA/Ca
- Source: Barriered Animal Breeding Unit, Alderley Park (laboratory B); Harlan Olac Ltd., Bicester, Oxon (laboratory A, C, D)
- Age at study initiation: approx. 8-12 weeks

ENVIRONMENTAL CONDITIONS
- no details
Vehicle:
other: acetone:olive oil, 4:1 v/v and dimethylformamide (DMF)
Concentration:
5, 10, 25, and 50 %
No. of animals per dose:
4
Details on study design:
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
The proliferative activity of lymph node cells (LNC) was expressed as the number of radioactive disintegrations per minute (dpm) per lymph node for each experimental group. The ratio of 3HTdR incorporation by LNC of test lymph nodes relative to that recorded for control lymph nodes test/control (T/C) ratio was calculated for each test group. A test chemical was regarded as positive in the LLNA, if the following criteria were fulfilled:
1. Exposure to at least one concentration of the chemical resulted in an incorporation of 3HTdR at least threefold greater than that recorded in control mice.
2. The data were not incompatible with a conventional biological dose response.

TREATMENT PREPARATION AND ADMINISTRATION:
Groups of mice (n=4) received 25 µL of one of three concentrations of the test chemical on the dorsum of both ears daily for three consecutive days. Control mice received an equal volume of the relevant vehicle alone.
Five days after the initiation of exposure, all mice were injected intravenously via the tail vein with 250 µL of phosphate-buffered saline (PBS) containing 20 µCi of [3H]methyl thymidine (3HTdR: specific activity 2 Ci/mmol, Amersham International, Amersham, UK). Five hours later the mice were sacrificed and the draining (auricular) lymph nodes were excised and pooled for each experimental group. Single-cell suspensions of lymph node-cells (LNC) were prepared by gentle mechanical disaggregation through stainless steel gauze (200 mesh size). The pooled LNC were pelleted by centrifigation at 190 g for 10 min, washed twice with 10 mL of PBS and resuspended in 3 mL of 5 % trichloroacetic acid (TCA). Following overnight incubation at 4 °C, the precipitates were recovered by centrifugation, resuspended in 1 mL of TCA and transferred to 10 mL of scintillation fluid (Optiphase MP, LKB). 3HTdR incorporation was measured by beta-scintillation counting.
Key result
Parameter:
SI
Remarks on result:
other: T/C ratio: 8.2 - 18.1

LLNA results obtained at the collaborating laboratories for the inter-laboratory trial:

 

Conc. [%]

T/C ratio

 

Lab. A

Lab. B

Lab. C

Lab. D

5

-

10.7

-

-

10

9.0

14.8

13.8

12.8

25

8.2

18.1

11.0

8.6

50

toxic

-

11.7

9.9

Vehicle used by Lab.: A, B, D: acetone : olive oil; C: DMF

T/C ratios equal or greater than 3.0 indicate a positive LLNA result. 2 -Hydroxyethyl acrylate elicited positive LLNA responses in all four contributing laboratories.

The available data do not show a clear dose-response relationship. Thus, derivation of an EC3 value and quantification of the substance's sensitizing potency was not possible.

Due to the corrosive properties of the substance, all experimental data on skin sensitization are of restricted reliability, since local irritating effects can interfere with effects caused by skin sensitization.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The skin sensitising potential of test substance was investigated in an Interlaboratory study in four independent laboratories (Scholes et al., 1992). The Local Lymphnode Assay was conducted according to the method described by Kimber et al. (1989, 1991) and Basketter et al. (1991) with one small modification. In the study described here the animals received topical applications of test chemical on three consecutive days and the assay was terminated after 5 days. The application of the test substance (analytical purity: >= 98 %) at concentrations of 5, 10, 25, and 50 % in acetone:olive oil, 4:1 v/v and dimethylformamide (DMF) respectively resulted in an increase in isotope incorporation which was greater than 3-fold at the 5 % w/v concentration. The test substance elicited positive LLNA responses in all four contributing laboratories. Consequently, the test substance was shown to be a potential skin sensitizer.

The available data do not show a clear dose-response relationship, except for the data from one laboratory. Thus, derivation of an EC3 value and quantification of the substance's sensitizing potency was not possible.

In addition, the test substance was tested in the Guinea Pig Maximization test in the same Interlaboratory study (Scholes et al., 1992). Induction concentrations were 0.25 % (intradermal) and 5.0 % (topical); the challenge concentration was 1.0 %. Positive results were noted in 70% of the test animals at 24 and 48 hr after challenge. This result was confirmed by a GPMT conducted by Bio Dynamics Inc. for Union Carbide Corporation (1982). 10/10 animals treated with the test material exhibited dermal responses at the first reading after challenge. No significant dermal responses were seen in the six irritation control animals, thus confirming that the concentration used was non-irritating (Union Carbide Corporation, 1982).

Additionally, other studies on skin sensitisation are available showing both a sensitising potantial or a non-sensitising potential for the test substance, but overall based on all the presented data, the tested substance is considered to be a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, the substance has to be classified as Skin Sens. 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.