2-(dimethylamino)ethyl acrylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

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 402 (Acute Dermal 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
- Supplier: Norsolor (Group Orkem)
- Lot/batch No.: RN 107 - 26/05/88
- 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 (B.P. 109, 69210 L'Arbesle, France)
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: mean males 274±11 g, mean females 211±9 g
- Fasting period before study:
- Housing: in groups of 4 to 7 animals of the same sex per cage during the acclimatization period in sterilizable polycarbonate cages (48 x 27 x 20 cm) and individually during the study in sterilizable polycarbonate cages (37.5 x 23.5 x 19.3 cm)
- Diet: certified 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

Type of coverage:

semiocclusive

Vehicle:

paraffin oil

Details on dermal exposure:

TEST SITE
- Area of exposure: healthy intact skin of clipped back and flanks
- % coverage: approx. 10% (5 x 7 cm) of the total body surface
- Type of wrap if used: adhesive hypoallergic aerated semi-occlusive dressing attached to a gauze bandage


TEST MATERIAL
- Amount(s) applied: 2.12 ml/kg bw of undiluted TS in preliminary assay, 5 ml/kg bw of TS in paraffin oil in main study

Duration of exposure:

24 h

Doses:

Males: 200, 330, 500, 700, 980, 1400, 2000 mg/kg bw
Females: 700, 980, 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg: 5 males; 330 mg/kg: 5 males; 500 mg/kg: 5 males; 700 mg/kg: 5 males and 5 females; 980 mg/kg: 5 males and 5 females; 1400 mg/kg: 5 males; 2000 mg/kg, preliminary study: 5 males and 5 females; 2000 mg/kg, main study: 5 males and 5 females

Control animals:

other: The body weight gain of the treated animals was compared to a reference curve of the C.I.T. control animals with the same initial weight.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were observed frequently after the application of the TS and at least once a day during the observation period. Mortality was checked frequently just after the application of the TS and then at least twice a day during the observation period. Body weights were determined just before the application 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. Quarterly Journal of Pharmacy and Pharmacology, 1944, 117-123).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

419 mg/kg bw

95% CL:

253 - 593

Remarks on result:

other: No sex-related differences in toxicity.

Mortality:

The mortality was 0%, 60%, 60%, 60%, 100% and 100% in the males at the dose levels of 200, 330, 500, 700, 980 and 1400 mg/kg respectively. Mortality was recorded principally within the 24 hours following application of the test substance. The mortality was 100% at 2000 mg/kg.

Clinical signs:

other: A moderate to severe decrease in spontaneous activity was observed at all dose levels 4 - 6 h after treatment. The general behaviour of the surviving animals returned to normal on day 3 except for 1 animal found dead on day 7 at 330 mg/kg and another anim

Gross pathology:

During necropsy, the macroscopic examination performed on the main organs of the animals treated at dose levels of 200, 500, 980, 1400 and 2000 mg/kg did not reveal any abnormalities. The intestines of 1 animal which was found dead on day 7 at 330 mg/kg were seen to be haemorrhagic.

Any other information on results incl. tables

Cumulated mortality data:

Sex	Dose (mg/kg)	Volume (ml/kg)	day 1	day 2	day 5	day 7	day 15	Mortality (%)
Males	200	5	0	0	0	0	0	0
	330	5	0	2	2	3	3	60
	500	5	0	3	3	3	3	60
	700	5	1	3	3	3	3	60
	980	5	3	5	5	5	5	100
	1400	5	5	5	5	5	5	100
	2000	5	0	5	5	5	5	100
	2000	2.12	0	5	5	5	5	100
Females	700	5	0	2	2	2	2	40
	980	5	3	5	5	5	5	100
	2000	5	0	5	5	5	5	100
	2000	2.12	0	5	5	5	5	100
Males and females combined	700	5	1	5	5	5	5	50
	980	5	6	10	10	10	10	100
	2000	5	0	10	10	10	10	100
	2000	2.12	0	10	10	10	10	100

 

Applicant's summary and conclusion

Conclusions:

Under the experimental conditions used, the LD50 of the test substance administered by the dermal route in the rat was 419 mg/kg. No sex-related difference in toxicity was revealed.