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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Oct 2015 - 20 Jan 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

adopted in 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Behörde für Gesundheit und Verbraucherschutz, Hamburg, Germany

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:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Research Models and Services Germany GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks (males), 9 weeks (females)
- Weight at study initiation: 239 - 270 g (males) and 218 - 250 g (females)
- Fasting period before study: animals were fasted approximately 16 hours prior to administration.
- Housing: Enter as given in the study report. in groups of 2-3 animals of the same sex per cage in MAKROLON cages (type III plus), Granulated textured wood (Granulat A2, J. Brandenburg, Goldenstedt, Germany), cages were changed and cleaned twice a week.
- Diet: Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany)(analysis was performed); ad libitum (except for fasting period)
- Water: tap water; ad libitum (analysis was performed)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Example: 22 ± 3
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

(IN-LIFE DATES: From: 04 Nov 2015 To: 20 Jan 2016)

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: no vehicle (unchanged test item was used)

Mass median aerodynamic diameter (MMAD):

>= 3.373 - <= 3.629 µm

Geometric standard deviation (GSD):

>= 3.05 - <= 3.19

Remark on MMAD/GSD:

No smaller GSD values could be obtained with the test item supplied.

Details on inhalation exposure:

EXPOSURE SYSTEM
- dynamic inhalation chamber (air changes/h (≥ 12 times))
- nose-only exposure according to KIMMERLE & TEPPER
- The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds the animals in pyrex tubes at the edge of the chamber in a radial position.
- Actual dimensions of the Inhalation Chamber: Inner Diameter: 28.2 cm; Height: 64.6 cm; Volume: 40.3 L

ADMINISTRATION:
- The aerosol of the test item was generated using a spray-jet.
- The spray-jet was fed with compressed air (5.0 bar) from a compressor and with the test item using an infusion pump.
- At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the spray-jet in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
- Control of the constant supply of compressed air and the exhaust via a manometer or an air-flow meter, respectively.
- The oxygen content in the inhalation chamber was 21% v/v.
- Particle size distribution (determined via a cascade impactor): See Table 1 under "any other information on materials and methods incl. tables"

CLASS METHOD
- Rationale for the selection of the starting concentration: Maximum recommended concentration

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrical

Duration of exposure:

4 h

Concentrations:

0.52, 1.05 or 5.06 mg/L air

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily until all symptoms subsided, thereafter each working day, and individual body weights were determined before the exposure on test day 1 and on test days 2, 4, 8 and 15 and at the time of death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma, changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern); determination of lung weights

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.5 - < 1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

5.06 mg/L air: 3/3 males and 3/3 females died
1.05 mg/L air: 3/3 males and 3/3 females died
0.52 mg/L air: No mortality.
For details refer to Table 2 under "any other information on results".

Clinical signs:

other: 5.06 and 1.05 mg/L air: moderately reduced motility, moderate ataxia, slight tremor, severe dyspnoea, lacrimation and vocalisation in 3/3 males and 3/3 females 0.52 mg/L air: slightly reduced motility, slight ataxia, slight tremor, moderate dyspnoea, lacr

Body weight:

5.06 and 1.05 mg/L air: all animals died prematurely
0.52 mg/L air: No inhibition of body weight gain in 3/3 males and 3/3 females.

Gross pathology:

5.06 and 1.05 mg/L air: Necropsy revealed oedematous or emphysematous lungs in 3/3 males and 3/3 females (refer to Table 3 under "any other information on results").
0.52 mg/L air: No change at necropsy.

Other findings:

Organ weights (lung tissue) were determined. Refer to Table 3 under "any other information on results".

Any other information on results incl. tables

Table 2: Table for acute inhalation toxicity

Target Concentration [mg/L air]	Mortality	Clinical Signs
	N*	N*
Males
0	0/5	0/5
1.337	0/5	0/5
2.871	0/5	0/5
Females
0	0/5	0/5
1.337	0/5	0/5
2.871	0/5	0/5

*N= Number of animals/ number of animals used

Table 3: Necropsy findings

Target concentration [mg/L air]	Animal (sex/number)	Tissue	Finding	Organ Weight (lung) [g]
5.06	m / 1	lung	oedematous	1.73
	m / 2	lung	oedematous	1.92
	m / 3	lung	oedematous	2.53
	f / 1	lung	emphysematous	4.02
	f / 2	lung	oedematous	1.78
	f / 3	lung	emphysematous	4.33
1.05	m / 1	lung	oedematous	2.18
	m / 2	lung	oedematous	1.90
	m / 3	lung	oedematous	3.78
	f / 1	lung	oedematous	2.62
	f / 2	lung	oedematous	2.11
	f / 3	lung	oedematous	2.70
0.52	m / 1	lung	none	1.56
	m / 2	lung	none	1.72
	m / 3	lung	none	1.44
	f / 1	lung	none	1.19
	f / 2	lung	none	1.23
	f / 3	lung	none	1.21
m = male; f = female

 

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS Category 3 (H331) according to Regulation (EC) No 1272/2008

Conclusions:

CLP: Acute Inhal. 3, H331