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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982-04-16 through 1982-07-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
BASF Test (internal standard method). In principle, the methods described by OECD TG 403 were used.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(E)-3-formylbut-2-enyl acetate
EC Number:
247-825-4
EC Name:
(E)-3-formylbut-2-enyl acetate
Cas Number:
26586-02-7
Molecular formula:
C7H10O3
IUPAC Name:
(2E)-3-methyl-4-oxobut-2-en-1-yl acetate
Details on test material:
- Name of test material (as cited in study report): C5-Acetat (2-methyl-4-acetoxybut-2-en-1-ol-1-al; ca. 98% trans, 2% cis)
- Physical state: liquid; colourless to slightly yellow
- Analytical purity: 98-99%
- Impurities (identity and concentrations): no data
No further data.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male and female Wistar rats (SPF/CHbb:Thom)
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: mean weights: 226 +/- 42 g (males); 170 +/- 17 g (females)
- Fasting period before study: no data
- Housing: 5 per cage, mesh wire cages (type DIII, Becker)
- Diet (ad libitum): SSNIFF R 10 Pellet, Ssniff-Versuchstierdiäten GmbH, Soest, Germany
- Water (ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
No further data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose-inhalation system INA 20 (BASF AG)
- Exposure chamber volume: ca. 55 l
- Method of holding animals in test chamber: animals are placed in glass tubes with their snouts projected into the inhalation chamber
- System of generating particulates/aerosols: infusion pumps UNITA I (Braun) and UNFU 362 (INDIGEL, Switzerland) and Two-compound nozzle 970 (Schlick). A constant amount of the test substance was conducted to the nozzle; the liquid aerosol was generated using pressed air (1.2 bars) and the aerosol was conducted to the inhalation system.
- Method of particle size determination: Particle size analysis was performed with an Andersen Stack Sampler Mark III. Samples of the inhalation mixture were collected by an impactor; the content of the impactor was analyzed by gas chromatography.

TEST ATMOSPHERE
- Brief description of analytical method used: quantitative determination of the aerosol concentrations was made by gas chromatography (GC HP 5840 A, Hewlett Packard)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 93% of the aerosol particles are able to reach alveolar tissue after inhalation.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.2 µm / 2.8
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal concentrations: 1.68, 8.4, 9.1, 18.9 mg/l
analytically determined concentrations (mean +/- SD): 0.64 +/- 0.14, 2.8+/- 0.32, 4.0 +/- 0.11, 4.9 +/- 0.28 mg/l
No. of animals per sex per dose:
10 males and 10 females per dose group
12 animals in the control group
Control animals:
other: a control group of 12 rats was exposed to air.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed prior to exposure, after 7 days and at the end of the observation period. Clinical observations were monitored on working days. Lethality was monitored daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Statistical evaluation was made in accordance with the Probit analysis by Finney [Finney DJ (1971). Probitanalysis 1971, pp. 1-150. Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1].

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3.6 mg/L air (analytical)
95% CL:
3.1 - 4.1
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
3.57 mg/L air (analytical)
95% CL:
3 - 4.1
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
3.63 mg/L air (analytical)
95% CL:
1.9 - 5.1
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
14 mg/L air
Exp. duration:
1 h
Remarks on result:
other: calculated
Sex:
male
Dose descriptor:
LC50
Effect level:
14 mg/L air
Exp. duration:
1 h
Remarks on result:
other: calculated
Sex:
male
Dose descriptor:
LC50
Effect level:
15 mg/L air
Exp. duration:
1 h
Remarks on result:
other: calculated
Mortality:
Mortality rates:
group 1: 10/10 males; 8/10 females
group 2: 5/10 males; 5/10 females
group 3: 2/10 males; 3/10 females
group 4: 0/10 males; 0/10 females
All deaths occurred within 2 days after exposure.
For details, see table below.
Clinical signs:
other: Groups 1, 2 and 3: restlessness, eyelid closure, serous ocular and nasal secretion, salivation, redness of the ears and extremities during exposure; reddish encrustation of the nose, slight serous nasal secretion, prone position, squatting posture after
Body weight:
Body weight gain was significantly retarded in group-2 males during the first week of post-observation. Males of groups 3 and 4 showed slight retardation of body weight gains during this period. Body weight gains of all females showed only slight alterations during post-observation week 1.
Gross pathology:
Findings in decedents (males and females):
Group 1: multiple secretory smears at the fur of the abdomen, snout, extremities and testes and sporadically centroacinar fatty degeneration of the hepatocytes.
Group 2: pulmonary emphysema, multiple pulmonary edemas, sporadically gaseous content of the stomach and intestine, spotted clay-like discoloration of the liver.
Group 3: pulmonary edema, sporadical lung emphysema, sporadical clay-like discoloration of the liver, acute dystrophy, fatty necrosis.

No abnormalities were observed in survivors sacrificed at the end of the study.

Any other information on results incl. tables

Table 2:Mortality data

Lethality time

Group

1

(4.9 mg/l)

2

(4.0 mg/l)

3

(2.8 mg/l)

4

0.64 mg/l)

no. of dead animals / no. of exposed animals

m

f

m

f

m

f

m

f

4 h

8/10

5/10

2/10

2/10

0/10

0/10

0/10

0/10

1 d

9/10

6/10

4/10

3/10

2/10

2/10

-

-

2 d

10/10

8/10

5/10

5/10

-

3/10

-

-

7 d

-

-

-

-

-

-

-

-

14 d

-

-

-

-

-

-

-

-

total mortality

18/20

10/20

5/20

0/20

 

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information