2-[[(butylamino)carbonyl]oxy]ethyl acrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 - 20 Feb 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Gyógyszerészeti és Egészségügyi Minőség- és Szervezetfejlesztési Intézet (National Institute for Quality- and Organizational Development in Healthcare and Medicines), Budapest, Hungary

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[[(butylamino)carbonyl]oxy]ethyl acrylate

EC Number:

264-036-0

EC Name:

2-[[(butylamino)carbonyl]oxy]ethyl acrylate

Cas Number:

63225-53-6

Molecular formula:

C10H17NO4

IUPAC Name:

2-[[(butylamino)carbonyl]oxy]ethyl acrylate

Test animals

Species:

rat

Strain:

other: Crl:WI BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXI COOP ZRT., Budapest, Hungary
- Age at study initiation: 11 weeks old
- Weight at study initiation: 207-228 g
- Fasting period before study: The day before treatment the animals were fasted.
- Housing: group caging (3 animals/cage), laboratory bedding, type II polypropylene/polycarbonate cages
- Diet: ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, Soest Germany
- Water: tap water from municipal supply; ad libitum
- Acclimation period: 26-28 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sunflower oil (Helianthi annui oleum raffinatum)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL and 500 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Formulations were prepared just before the administration and stirred continuously during the treatment.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Starting dose was selected on the basis of the available information about the test item.
A full test was performed. The acute toxic class method was carried out involving a stepwise procedure with the use of 5000 mg/kg bw as the starting dose in one female rat. This animal died and then dosing was proceeded at 2000 mg/kg in three females in accordance with the criteria of Annex 3 of OECD Guideline No. 423. No animal died in the second step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. One animal died in the third step, only, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Doses:

2000 and 5000 mg/kg bw

No. of animals per sex per dose:

5000 mg/kg bw (1st step): one female
2000 mg/kg bw (2nd step): 3 females
2000 mg/kg bw (3rd step): 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter. The body weights were recorded on day 0 (just before the treatment), on day 1, on day 7 and on day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

5000 mg/kg bw (1st step): 1/1 female died on Day 1
2000 mg/kg bw (2nd step): 0/3 females died
2000 mg/kg bw (3rd step): 1/3 females died on Day 7

Clinical signs:

other: 5000 mg/kg bw (1st step): clinical signs of reaction comprised of decreased activity (4 cases of 5 observations), abnormal gait (4/5), decreased righting reflex (3/5), decreased grip- and limb tone (4/5), decreased body tone (3/5), decreased abdominal ton

Gross pathology:

5000 mg/kg bw (1st step): no external findings; autolysis was observed
2000 mg/kg bw (2nd step): no external findings; in 2/3 females slight hydrometra and in 1/3 animals severe hydrometra was detected
2000 mg/kg bw (3rd step): no external findings; in the female which died on Day 7 autolysis was observed, the two survivors showed moderate hydrometra

Any other information on results incl. tables

Table 1. Acute oral toxicity

Dose [mg/kg bw]	Mortality	Clinical signs
	N*	N*
Females
5000 (1st step)	1/1	1/1
2000 (2nd step	0/3	0/3
2000 (3nd step)	1/3	0/3

*N= Number of animals/ number of animals used

 

 

Applicant's summary and conclusion

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified