4-morpholinecarbaldehyde

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Jan 2016 - 26 Mar 2016

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-morpholinecarbaldehyde

EC Number:

224-518-3

EC Name:

4-morpholinecarbaldehyde

Cas Number:

4394-85-8

Molecular formula:

C5H9NO2

IUPAC Name:

morpholine-4-carbaldehyde

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 93973556P0
- Expiration date of the lot/batch: 08 Apr 2017


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room termparture
- Stability under test conditions: The stability of the test substance under storage conditions over the test
period was guarenteed by the sponsol.
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 11 weeks
- Weight at study initiation: female 200,5 g; male 239,5 g
- Housing: air-conditioned rooms; TYP III polycarbonate cages; wooden gnowing blocks as
enrichment, single housing or up to 5 animals, dust-free wooden bedding
- Diet: Kliba laboratory diet, mouse/rat maintenance "GLP" 12mm pellets ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before exposure

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70 %
- Air changes : 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Test-substance preparation:
The test substance was dosed unchanged.
The test substance was stirred in its container before a sample for aerosol generation was taken.
Equipment: Two-component atomizer Mod. 970 (stainless steel, Schlick) Continuous infusion pumps PHD Ultra (Harvard Apparatus, Inc., Holliston, Massachusetts, U.S.A.)
Generation technique: A liquid aerosol was generated.
The aerosol was produced by continuously pumping amounts of the test substance into the two-component atomizer. Using compressed air, the aerosol was generated with the atomizer inside the exposure system.
Nose-only inhalation system INA 20 (glass-steel construction, BASF SE, volume V 55 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 aerosols.
Conditioned air:
The central air conditioning system provides cold air of about 15°C. This cold air passes through an activated charcoal filter, is adjusted to room temperature of 20 to 24°C and passes through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air was used to generate inhalation atmospheres.
Compressed air:
Compressed air was 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 passing through a 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 laboratories via pipes, where the pressure is reduced to 6 bar. In the laboratory, the compressed air can be taken as required.
Exhaust air:
The exhaust air was 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 exposure, the following scheduled parameters were recorded four times at about 1-hour intervals:
Supply air flow (compressed air): (from a central air-conditioning system) 1.5 m³/h
The flow was adjusted and continuously measured with a flowmeter (Yokogawa).
Exhaust air flow: 1.3 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 27 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 10 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 with a digital thermometer (Testo).
Relative humidity: The relative humidity in the inhalation system was measured with a dielectric probe (Testo).
Particle size analysie
EACD 50% (effective aerodynamic cutoff diameter 50%) defines the separation characteristic of each impactor stage. 50% of particles with the EACD given are deposited in the pertinent impactor stage; the remainder has reached one of the following stages.
MMAD (mass median aerodynamic diameter) is the calculated aerodynamic diameter which divides the size distribution in half when measured by mass.
Geometrical standard deviation (GSD) is the ratio of the estimated 84 percentile to the 50 percentile and indicates the slope of the cumulative particle size distribution curve.
Sample 1 MMAD (μm) 2,7 GSD 3.0
Sample 2 MMAD (µm) 3.0 GSD 3.0

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5,319 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
- Feed and Water: A check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays.
- Body weight determination: Individual body weights once during the acclimatization period, shortly before exposure (day 0) and at least on days 1, 3 and 7,
and before the sacrifice of the animals at the end of the observation period.
- Signs: Clinical observations were recorded for each animal before exposure, separately several times during exposure (usually hourly) and after exposure. At least once daily on the preexposure day and during the post exposure observation period.
- Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Pathology: At the end of the observation period the animals were sacrificed with CO2-inhalation in a chamber with increasing concentration over time, and were subjected to gross-pathological examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 5.319 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

no mortality occurred

Clinical signs:

other: abdominal respiriation, intermittent respiration indicating local irritation effect, piloerection and substance contaminated fur

Body weight:

the mean body weights decreased on the first post exposure observation day but decreased thereafter.

Gross pathology:

no gross pathological abnormalities were detected during necropsy in the animals at the termination of the study

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the current study conditions, the LC50 value was > 5.3 mg/l in male and female rats after 4 hour inhalation to liquid aerosol of the test-substance.

Executive summary:

Based on the results observed and by applying the evaluation criteria it was concluded that N-formylmorpholine don´t need to be classified as toxic after single inhalation application according to Regulation 1272/2008/EC. (BASF, 2016).