Registration Dossier

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:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.56 mg/L air (analytical)
95% CL:
0.47 - 0.66
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 0.6 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: (following interpolation)
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:
- 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, reddish nose discharge.
- after exposure: flank respiration, reddish, smeared snout area (subsequently crusted; evidence of blood), anogenital region smeared with urine. Additional findings in the mid and high dose animals: dragging respiration with respiratory sounds, reduced general state, piloerection, reduced dedecation. Additional findings in high dose animals only: gasping, high stepping and unstable gait, apathy, squatting posture, reduced care on fur. Strength and duration of the symptoms were dose-dependent: Animals of the low dose group were free from symptoms from day 4 on. Surviving animals of the mid and high dose groups showed symptoms until the end of the observation period.
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).