Propanoic acid, 2-hydroxy-2-methyl-, 2-propen-1-yl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Full study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

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:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

EC Number:

700-908-3

Cas Number:

19444-21-4

Molecular formula:

C7H12O3

IUPAC Name:

prop-2-en-1-yl 2-hydroxy-2-methylpropanoate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Biological Research Laboratories, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: Young adult (approximately 8-12 weeks)
- Weight at study initiation: 208 to 265 g
- Fasting period before study:
- Housing: Individual
- Diet: Available ad libitum
- Water: Available ad libitum from bottles
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50% ± 20%
- Air changes (per hr): 13-14/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% in 0.1% polysorbate

Details on dermal exposure:

TEST SITE
- Area of exposure & % coverage: An area of about 6 x 6 cm (10 % of body surface)on the back of each rat was shaved using an electric clipper.
- Type of wrap if used: After test material was applied the area was covered with a gauze-lined semiocclusive dressing fastened around the
trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
After an exposure time of 24 hours, the skin ws cleaned with lukewarm water.

TEST MATERIAL and VEHICLE
Dose level: 200mg/kg, 400mg/kg and 2000mg/kg
Dose selecion: The higher dose level was selected based on the OECD/EEC guidelines of 2000mg/kg for the limit test.
Vehicle: 0.5 % (w/v) carboxymethylcullulose in 0.1 %(w/v)aqueous polysorbate 80
Ratio test article to vehicle: 200mg/kg: 602mg test article with vehicle ad 12g
400mg/kg: 1203mg test article with vehicle ad 12g
2000mg/kg 10002mg test article with vehicle ad 20g
Volume/quantity applied: 400 mg per 100g body weight
Frequency of adminstration: One single dose.

Duration of exposure:

4 hours

Doses:

200, 400 and 2000mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Period of observation: 14 days after treatment.
Clinical observations: Checked and recorded individually within first two hours after dosing, then daily for the duration of the
observation period.
Local tolerances: The application site was examined daily for signs of dermal irritation. Any dviations from normal were
recorded using Draize scale.
Mortality: Checked twice daily, morning and afternoon.
Body weight: Measured and recorded immediatley before dose adminstration, on days 7 and 14.
Necropsy: All animals sacrificed at test termination wre subjected to a necroscopy examination. If animals were found dead or sacrificed in extremis, they were necropsied.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 200 - < 400 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 400 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals in the 2000mg/kg dose groups were found dead on the application day. Four males (no. 6, 8, 9 and 10) and one female (no. 108) in the 400 mg/kg dose groups were found dead 1 day after patch removal. The remaining male (no. 7) in the 400 mg/kg dose group was killed for animal welfare reasons 1 day after patch removal. There was no mortality at 200 mg/kg.
Therefore, the following acute dermal LD50 values were determined for CA 2215 A (Intermediate of CGA 276854):
LD50 in male rats: Greater then 200, lower than 400 mg/kg body weight
LD50 in female rats: Greater then 400, lower than 2000 mg/kg body weight
LD50 in rats of both sexes: Greater then 200, lower than 20000 mg/kg body weight

Clinical signs:

other: On the application day, moderate hypoactivity was seen in all animals in the 2000 mg/kg dose groups, and in the 400 mg/kg dose groups, moderate diarrhea in all animals in the 2000 mg/kg dose groups and rinorrhea in two males (no. 1 and 2) and one female (

Gross pathology:

Necropsy examinations revealed a reddish small intestine with dilatation, a reddish large intestine with dilatation and a reddish caecum with dilatation in all animals in the 2000 mg/kg dose groups, and a reddish thymus in two males (no. 8 and 10) and in one female (no. 108) in the 400 mg/kg dose groups.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Acute tox 3 Criteria used for interpretation of results: EU

Conclusions:

The following acute dermal LD50 values were determined for CA 2215 A (Intermediate of CGA 276854):
LD50 in male rats: Greater then 200, lower than 400 mg/kg body weight
LD50 in female rats: Greater then 400, lower than 2000 mg/kg body weight
LD50 in rats of both sexes: Greater then 200, lower than 20000 mg/kg body weight

Executive summary:

Groups of 5 male and 5 female rats were administered a single dose of CA 2215 A (Intermediate of CGA 276854) by dermal application at dose level of 200mg/kg, 400mg/kg and 2000mg/kg for 24 hour period under semiocclusive conditions, followed by a 14 day post treatment observation period. 

All animals in the 2000mg/kg dose groups were found dead on the application day. Four males and one female in the 400 mg/kg dose group were found dead 1 day after patch removal. The remaining male in the 400 mg/kg was killed for animal welfare reasons 1 day after patch removal. There was no mortality at 200 mg/kg. 

On the application day, moderate hypoactivity was seen in all animals in the 2000 mg/kg dose groups, and in the 400 mg/kg dose groups, moderate diarrhea in all animals in the 2000 mg/kg dose groups and rinorrhea in two males and one female in the 2000 mg/kg dose groups. Slight hypoactivity, tremor and ataxia were seen on day 1 after patch removal in one female in the 400 mg/kg group. All surviving females in the 400 mg/kg group appeared normal by day 2 after treatment. There were no remarkable clinical observations in the 200 mg/kg groups. There were no remarkable findings at the application site for most animals. One male in the 200 mg/kg group presented with scurf and a crust from day 8 to the end of the observation period. 

A loss of body weight was recorded in all surviving females in the 400 mg/kg dose group during the first week of application and in one female in the 200 mg/kg dose group during the second week after application. 

Necropsy examinations revealed a reddish small intestine with dilatation, a reddish large intestine with dilatation and a reddish caecum with dilatation in all animals in the 2000 mg/kg groups, and a reddish thymus in two males and in one female in the 400 mg/kg. 

The following acute dermal LD50 values were determined for CA 2215 A (Intermediate of CGA 276854):

LD50 in male rats:                      Greater then 200, lower than 400 mg/kg body weight

LD50 in female rats:                   Greater then 400, lower than 2000 mg/kg body weight

LD50 in rats of both sexes:        Greater then 200, lower than 20000 mg/kg body weight