methyl acrylate; methyl propenoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

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:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Methyl acrylate

EC Number:

202-500-6

EC Name:

Methyl acrylate

Cas Number:

96-33-3

Molecular formula:

C4H6O2

IUPAC Name:

methyl prop-2-enoate

Details on test material:

- Name of test material (as cited in study report): Methylacrylate
- Physical state: liquid /colorless, clear
- Analytical purity: 99.95 %
- Lot/batch No.: 011063eda0

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Haraln Laboratories B.V., Niederlande
- Age at study initiation: Young adult animals (male: approx. 8 weeks; female approx. 10 weeks)
- Weight at study initiation: animals of vomparable weight (+/- 20% of the mean weight)
- Housing: single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:for at least 5 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

Head-nose inhalation system INA 60 (glass-steel construction, BASF SE, volume V ≈ 90 L): the animals were restrained in glass tubes and their snouts projected into the inhalation system.
The homogenous distribution of test substance atmosphere in this inhalation system has been verified with model vapors.
GENERATION OF TEST ATMOSPHERE
Conditioned air:
Central air conditioning system provides cold air of about 15°C. This cold air will pass through an activated charcoal filter, be adjusted to room temperature of 20 to 24°C and pass through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air is used to generate inhalation atmospheres.
Compressed air:
Compressed air is produced by an oil-free compressor (HT 6, Josef Mehrer GmbH & Co KG, Germany). For this purpose, air is filtered by an inlet air strainer and introduced into the compressor. After passed through an second ultra filter (SMF 5/3, 108 mm, Donalson), the compressed air (15 bar) is stored in a storage of 1500 or 5000 L. The compressed air is conducted to the labs via pipes, where the pressure is reduced to 6 bar. In the lab, thecompressed air can be taken as required.
Exhaust air:
The exhaust air is filtered and conducted into the exhaust air of the building. The exposure system was located inside an exhaust cabin in an air-conditioned laboratory. During each exposure, the following parameters were recorded four times at about 1-hour intervals:
Supply air flow (conditioned air): 3.0 m³/h (from a central air-conditioning system) The flow was adjusted and continuously measured with a flowmeter (Yokogawa).
Exhaust air flow: 2.6 m³/h The flow was adjusted and continuously measured with a flowmeter (Yokogawa).

The lower amount of exhaust air, which was adjusted by means of a separate exhaust air system, achieved a positive pressure inside the exposure system. This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.
An air change of about 33 times per hour can be calculated by dividing the supply air flows by the volume of the inhalation system.
The animals were exposed to the inhalation atmosphere for 4 hours plus equilibration time of the inhalation systems (t99 about 8 min).
No surveillance of the oxygen content in the inhalation system was performed. The air change was judged to be sufficient to prevent oxygen depletion by the breathing of the animals, and the concentration of the test substance used could not have a substantial influence on oxygen partial pressure.
Temperature: The temperature in the inhalation system was measured continuously with a digital thermometer.
Humidity: The humidity in the inhalation system was measured with a dielectric probe (Testo).

Duration of exposure:

4 h

Concentrations:

10.832 mg/l

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight on the animals was checked before the beginning of the study and at least on days 1,3 and 7 and before the sacrifice of the animals at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals were made daily.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

< 10.832 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

5 males and 2 females died at the test concentration

Clinical signs:

other: depressed respiration, abdominal respiration, gasping, respiration sounds, red encrusted eye and nose, salivation, skin pale, piloerection, hyperexcitability, tremor and poor general state. Findings were observed from hour 2 of exposure through to the stu

Body weight:

No body weight data present in the male animals because all males died. The mean body weights of the surviving female animals decreased during the first post exposure observations day and increased from study day 3 onward.

Gross pathology:

No gross pathological abnormalities were detected during necropsy in the female animal that was found dead on study day 0 after exposure. During necropsy of the male animals that was found dead on study day 1 few dark-red discolorations in the lung with partly sunken surface and severe
dilation with a gaseous content was noted. Another male animal which also died on study day 1, showed only severe dilation with a gaseous content. During necropsy of the three males that was found dead on study day 2, abnormal gaseous content of the stomach and intestine was noted. The one female animal that was found dead on study day 2 showed dark-red discoloration in the lung and abnormal gaseous content of the stomach and intestine. No gross pathological abnormalities were detected during the necropsy in the surviving three female animals at the termination of the post exposure period.

Any other information on results incl. tables

Results of analytical measurements:

Sample No.               Analytical concentration (mg/L)

101                                                         9.961

102                                                        10.990

103                                                        11.310

104                                                        11.067

Mean                                                      10.8320

Last fritted glass flask (sample 105)          0.000

Mean + Last fritted glass flask              10.8320

Mean (rounded)                                    10.832

Standard deviation of the mean                0.596

Nominal concentration                             10.4