Methacrylaldehyde

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (non-GLP)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylaldehyde

EC Number:

201-150-1

EC Name:

Methacrylaldehyde

Cas Number:

78-85-3

Molecular formula:

C4H6O

IUPAC Name:

methacrylaldehyde

Details on test material:

Methacrolein, CAS No.: 78-85-3
Purity: 96 - 97 %
Stabiliser: 200 ppm hydrochinone
Batch from 1987-06-10
Expiration date September 1987

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, 7950 Biberach
- Age at study initiation: 8-9 weeks
- Weight at study initiation: males 268 ± 7.4 g, females 200 ± 5.4 g
- Fasting period before study: not reported
- Housing: in wire mesh cages type D III (Firma Becker)
- Diet (e.g. ad libitum): KLIBA laboratory diet for rats/mice 24 343-4 10 mm pellet, Klingentalmühle AG, CH-4303 Kaiseraugst, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light


IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test substance was used undiluted.
A mixture of vapour with air was generated by using an infusion pump INFU 362 CINDIGEL/ Switzerland and a thermostated glass vaporizer (BASF).
The test substance/air vapour was generated separately for each dose group. The vapours were then mixed with fresh air and were pipelined to the inhalation system. The air flow was uniformly 3000 L/h for each group.
The inhalation chambers were situated in air conditioned rooms, the temperature was 19-25 °C.
The suction air flow was ca. 3 % higher than the supply air flow.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Analysis: Gas chromatography (GC HP 5840 A, Hewlett Packard) Glass Column, length: 2 m, inner diameter 2 mm, separation phase: 15 % Ucon LB 550 x, substrate Chromosorb WIHP, 80/100 mesh, carrier gas helium, carrier gas flow: 34 mL/min, hydrogen: 30 mL/min

Duration of exposure:

4 h

Concentrations:

0.19, 0.44 and 0.71 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Whole-body exposure system in separated wire-mesh cages (1 animal per cage unit) in a glass-steel inhalation chamber (volume: 200 L)
Sampling for chemical analysis: ca. 1 sample per hour and per concentration, samples taken near the snouts of the animals
Body weight determination before administration, 7 days p.a. and 14 days p.a.
Animal observation at least once daily on working days
Necropsy of all animals with gross pathological examination

Statistics:

Statistical evaluation of a concentration-effect-relationship according to probit analysis (Finney. D.J.: Probitanalysis 1971, p. 1-150. Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1)

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.56 mg/L air (analytical)

95% CL:

0.47 - 0.66

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 0.6 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: (following interpolation)

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

ca. 0.5 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: (following interpolation)

Mortality:

0.19 mg/L: 0/10
0.44 mg/L: 1/10
0.71 mg/L: 9/10
see also below (remarks on results)

Clinical signs:

other: - during exposure: eyelid closure, accelerated and irregular to intermittent respiration, aqueous discharge of eyes and nose, salivation, anaemic aspect, squatting posture. Additional findings in the mid and high dose animals: gasping, apathy, reddis

Body weight:

0.19 mg/L: Mean data (males and females) indicate body weight gain in both weeks p. a. Body weight development for both sexes markedly delayed until day 7 compared to historical control data.
0.44 mg/L: Body weight gain was noted in males in both weeks p. a (mean data). There was a body weight reduction in female's mean data only in the first week p. a. Body weight development for both sexes markedly delayed until day 7 compared to historical control data.
0.71 mg/L: Body weight loss was observed in the surviving male in the first and second week p. a. There was also a body weight reduction in the last female animal after 7 days p. a.

Gross pathology:

Deceased animals:
0.44 mg/L (1 female): lung: acute emphysema, hardened lobus cranialis
0.71 mg/L (males and females): general congestion hyperaemia, lung: some animals with spotted pneumonia with edge emphysema or atelectical origins
Terminal necropsy:
0.19 and 0.44 mg/L (males and females): no substance related changes
0.71 mg/L: (1 male): lung: emphysematic, lobus cardiacus with pneumonic areas

Any other information on results incl. tables

Cumulative Mortality

treatment	0.19 mg/L		0.44 mg/L		0.71 mg/L
day	male	female	male	female	male	female
0	0/5	0/5	0/5	0/5	0/5	0/5
1	0/5	0/5	0/5	0/5	3/5	2/5
2	0/5	0/5	0/5	1/5	4/5	2/5
7	0/5	0/5	0/5	1/5	4/5	4/5
14	0/5	0/5	0/5	1/5	4/5	5/5
sum	0/10		1/10		9/10

Applicant's summary and conclusion

Executive summary:

In an acute inhalation toxicity study (OECD Guideline 403), groups of young adult Wistar rats (5/sex) were exposed by inhalation to Methacrolein for 4 hours to a whole body route at concentrations of   0.19, 0.44, or 0.71  mg/L.  Animals then were observed for 14 days.

 

A total number of 9 animals (4/5 males, 5/5 females) of group 3 (0.71 mg/L) deceased until the end of the study. First deaths (3/5 males, 2/5 females) of this group were recorded on Day 1.

 

A single female of group 2 (0.44 mg/L) died on Day 2.

 

There were no deaths in group 1 (0.19 mg/L).