4-hydroxybutyl acrylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 Mar 2005 to 27 Apr 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

December 29, 1992

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxybutyl acrylate

EC Number:

219-606-3

EC Name:

4-hydroxybutyl acrylate

Cas Number:

2478-10-6

Molecular formula:

C7H12O3

IUPAC Name:

4-hydroxybutyl acrylate

Specific details on test material used for the study:

- Name of test material: Butanediolmonoacrylate
- Chemical name: 2-Propenoic acid, 4-hydroxy ester
- CAS No.: 2478-10-6
- Substance No.: 04/0667-1
- Analytical purity: 99.3 % (The analyses of the test substance were carried out at the Analytical Department of BASF AG, Germany, Analytical Report No. 04L00264.)
- Lot/batch No.: 010078 EDA 0

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar/ HanRcc: WIST(SPF)
- Source: RCC Ltd. Laboratory Animal Services, Woelferstrasse 4, CH-4414 Fuellinsdorf, Switzerland
- Age at study initiation: Young adult animals (male animals approx. 8-10 weeks, female animals approx. 12-14 weeks)
- Weight at study initiation: males 257 g, females 225 g (mean)
- Fasting period before study: no
- Housing: single housing
- Diet (ad libitum): Kliba Labordiaet (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland
- Water (ad libitum): tap water
- Acclimation period: Acclimatization for at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
(About 40 cm2 corresponding to at least 10 % of the body surface)
- Type of wrap if used: The bandage consisted of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with warm water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount applied: 1.92 mL/kg

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays and on public holidays.
Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study.
Recording of signs and symptoms were performed several times on the day of administration, and at least once each workday for the individual animals.

- Necropsy of survivors performed: yes
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice of all surviving animals.

- Other examinations performed: clinical signs, body weight, organ weights, histopathology of the application site

- Scoring of skin findings according to Draize (1959) were conducted on each animal 30 - 60 minutes after removal of the semiocclusive dressing (day 1) and several times until the end of the study (last day of the observation period).

- Assessment of the skin findings: According to Draize JH (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.)

Statistics:

The binomial test (Snedecor GW, Cochran WG (1989). Statistical methods. 8th ed., Iowa State University Press/Ames) was used for the determination of the LD50.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality and no systemic clinical signs observed.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical observations were noted in the animals.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study, except in three females, where in the region of the application site skin lesions and surface incrustations were observed.
Histopathological examination of the skin of these animals revealed full thickness necrosis.

Other findings:

Local skin findings:
Two male animals showed no local effects. In the remaining three male animals and in all female animals the following skin effects were observed at the application site: very slight to well-defined erythema, very slight edema, (severe) scaling, eczematoid skin change and detachment of superficial altered skin layers in the region of eczematoid skin change with scar-like sleek and reddened skin underneath. Findings were observed from study day 5 until study day 14 (study termination).

Any other information on results incl. tables

Under the conditions of this study, the acute dermal median lethal dose (LD50) of butandiolmonoacrylat after dermal application was found to be greater than 2000 mg/kg body weight both in male and female rats.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met