Acrylic acid, monoester with propane-1,2-diol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

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.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The Local Lymph Node Assay: Results of a Final Inter-Laboratory Validation under Field Conditions.

Author:

Scholes EW et al.

Year:

1992

Bibliographic source:

J. Appl. Toxicol. 12: 217-222

Reference 2

Reference Type:

publication

Title:

Comparison of the Local Lymph Node Assay with the Guinea-Pig Maximization Test for the Detection of a Range of Contact Allergens.

Author:

Basketter DA & Scholes EW

Year:

1992

Bibliographic source:

Fd. Chem. Toxic. 30 (1): 65

Reference 3

Reference Type:

review article or handbook

Title:

Structure Activity Relationships in Skin Sensitization using the Murine Local Lymph Node Assay.

Author:

Ashby J et al.

Year:

1995

Bibliographic source:

Toxicology 103: 177-194

Materials and methods

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)

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxyethyl acrylate

EC Number:

212-454-9

EC Name:

2-hydroxyethyl acrylate

Cas Number:

818-61-1

Molecular formula:

C5H8O3

IUPAC Name:

2-hydroxyethyl acrylate

Details on test material:

- 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

In vivo test system

Test animals

Species:

mouse

Strain:

other: 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

Study design: in vivo (LLNA)

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.

Results and discussion

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: T/C ratio: 8.2 - 18.1

Any other information on results incl. tables

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. Based on the available data, it can be assumed that 2 -HEA is a sensitizer of moderate to strong potency according to the criteria proposed by the EU Expert Group (ECHA, R.8, May 2008).

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.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information