2-(dimethylamino)ethyl acrylate

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: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

2-(dimethylamino)ethyl acrylate

EC Number:

219-460-0

EC Name:

2-(dimethylamino)ethyl acrylate

Cas Number:

2439-35-2

Molecular formula:

C7H13NO2

IUPAC Name:

2-(dimethylamino)ethyl prop-2-enoate

Details on test material:

- Name of test material (as cited in study report): ADAME
- Purity: no impurities
- Physical state: colourless liquid
- Lot/batch No.: RN 107 - 26/05/88
- Supplier: Norsolor (Group Orkem)
- Storage condition of test material: + 4°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA CREDO
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: mean males: 180 ± 10 g; mean females 145 ± 11 g
- Fasting period before study: approx. 18 hours before TS administration
- Housing: in sterilizable polycarbonate cages (48 x 27 x 20 cm) covered with a non-corrosive wire mesh lid in groups of 4 to 7 animals of the same sex during acclimatization period and groups of 5 animals of the same sex per cage during the study
- Diet: pellet diet "Rat et Souris entretien A04 C" (U.A.R. 91360 Villemoisson-sur-Orge, France) ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: paraffin oil

Details on oral exposure:

ADMINISTRATION VOLUME: 10 ml/kg bw per dose group

Doses:

males: 80, 160, 320, 640, 2000 mg/kg bw
females: 160, 320, 2000 mg/kg bw

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs frequently after the administration of the TS and at least once a day during the observation period. Mortality was checked frequently just after the administration of the TS and at least twice a day during the observation period. The animals wre individually weighed just before the administration of the TS and then on day 5, day 8 and day 15.
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated according to FINNEY's method (E Weber, Grunden der biologischen Statistik, Gustav Fischer Verlag, Stuttgart 1972). The lower and upper limits of the confidence interval for a 95% probability threshold were calculated according to FIELLER's method (Fieller, A fundamental formula in the statistics of biological assay and some applications. Quaterly Journal of Pharmacy and Pharmacology, 1944, 117-123).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 455 mg/kg bw

95% CL:

247 - 1 072

Mortality:

Mortality was 0%, 0%, 20%, 80% and 100% respectively at the dose levels of 80, 160, 320, 640 and 2000 mg/kg in the males, and 0%, 60% and 100% at the dose levels of 160, 320 and 2000 mg/kg in the females.

Clinical signs:

other: A significant decrease in spontaneous activity was observed at all dose levels. The clinical signs appeared within minutes of treatment and persisted for 4 hours to 6 days depending on the dose administered in the surviving animals.

Gross pathology:

The autopsy performed on the animals sacrificed at the end of the study did not reveal any macroscopic abnormalities. In the animals found dead during the study, signs of haemorrhage were found in the stomach and the intestines (in 2 females at 320 mg/kg, in 4 males at 640 mg/kg and in all animals at 2000 mg/kg).

Any other information on results incl. tables

Cumulative mortality:

Sex	Dose (mg/kg bw)	Number of dead animals					Mortaliy (%)
		Day 1	Day 2	Day 5	Day 6	Day 15
Male	80	0	0	0	0	0	0
	160	0	0	0	0	0	0
	320	0	0	0	1	1	20
	640	4	4	4	4	4	80
	2000	5	5	5	5	5	100
Female	160	0	0	0	0	0	0
	320	2	3	3	3	3	60
	2000	5	5	5	5	5	100

Applicant's summary and conclusion

Conclusions:

Under these experimental conditions, the LD50 of the test substance administered by oral route in the rat was higher than 455 mg/kg. The lower and upper limits of the confidence interval for a probability threshold of 95% were 247 mg/kg and 1072 mg/kg, respectively. No difference in toxicity which could be sex-related was found.