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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Full study report with GLP compliance statement

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

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 Ltd, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: Young aduls (approximately 7-11 weeks)
- Weight at study initiation: 163-187 g
- Fasting period before study: Fasted overnight prior to dosing
- Housing: 5 same -sex animals per cage
- Diet : available ad libitum
- Water: availabale ad libitum from bottles.
- Acclimation period: 5days

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

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% in 0.1% aqueous polysorbate 80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/kg:404 mg test article with vehicle ad 20ml. 500mg/kg: 1251mg test article with vehicle ad 25 ml.

Volume applied by gavage: 10ml/kg

DOSE LEVELS: 200mg/kg (Females), 500mg/kg (both sexes)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: EU classification criteria and pre-test results.

Doses:

200 and 500mg/kg

No. of animals per sex per dose:

5 males and 5 females at 500mg/kg
5 females at 200mg/kg

Control animals:

no

Details on study design:

Period of observation: 14 days.
Clinical Observations: Checked and recorded individually at 1,3 and 5 hours after dosing, then daily for the duration of the observation period.
Mortality: Checked twice daily, morning and afternoon.
Body weight: Measured and recorded imediately before dose administration, then on days 7 and 14.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 200 - < 500 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 500 mg/kg bw

Based on:

test mat.

Mortality:

Four females (80%) (no. 101, 102, 103 and 105) in the 500mg/kg group were found dead 1 day after treatment. Therfore, the following acute oral LD50 values were determined for CA 2215 A (Intermediate for CGA 276854). Refer to Effect levels above.
Table 1.

Clinical signs:

other: On the treatment day through day 5, slight up to moderate piloerection was seen in four males (no. 1 2, 3, and 5) and slight up to severe piloerection in one male (no. 4). Slight up to severe piloerection was seen in all females in the 500mg/kg group on

Gross pathology:

Necropsy
Necropsy examinations revealed fibrinous adhesions in the abdominal cavity in all males and one female (no. 104) in the 500 mg/kg group. Organs involved were stomach, spleen and liver. Necropsy observations

Any other information on results incl. tables

Table 1 - Mortality

Males	No. of deaths	% of Deaths
Group 1 (500mg/kg)	0/5	0
Females
Group 1 (500mg/kg)	4/5	80
Group 2 (200mg/kg)	0/5	0

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

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

Conclusions:

Study results used to clasify under Regulation (EC) No. 1272/2008 Sectio n3.1 Acute Toxicity.
Classification determined Acute Tox. Cat. 3 - H301

Executive summary:

Groups of 5 male and 5 female rats were administered a single dose of CA 2215 A

(Intermediate of CGA 276854) (batch P.608005) by gavage at dose levels of 200 mgkg

(females) and 500 mgkg (both sexes), followed by a 14-day post-treatment observation

period.

Four females in the 500 mglkg group were found dead 1 day after treatment.

Piloerection of various intensity was seen in all males and all females on the treatment

day, and persisted up to day 5 in the males and day 7 in the surviving 500 mgkg

female. Hunched posture was seen in all animals on the treatment day, and in all males

and in the surviving female in the 500 mg/kg group on day 1 and 5 after treatment. In

the 500 mgkg groups, slight up to moderate hypoactivity was seen in two males and

slight up to severe hypoactivity was seen in three males and all females. All males

appeared normal by day 6 after treatment, the surviving female in the 500 mgkg group

appeared normal by day 8 after treatment, and all females in the 200 mgkg group

appeared normal by day 1 after treatment,

A loss of body weight was recorded in one male animal during the first week after

treatment.

Necropsy examinations revealed fibrinous adhesions in the abdominal cavity in all

males and in one female in the 500 mg/kg group. Organs involved were stomach, spleen

and liver.

The following acute oral LDso values were determined for CA 2215 A (Intermediate of

CGA 276854):

LDso in male rats: Greater than 500 mgkg body weight

LDsoin female rats: Greater than 200, lower than 500 mgkg body weight

LDso in rats of both sexes: Greater than 200, lower than 500 mgkg body weight