Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1978 - August 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
September 2009
Deviations:
not specified
Remarks:
Only limited information regarding animal acclimatization, animal husbandry and inhalation chamber conditions is given. Recods of bodyweights only performed on day 7 and 14 after exposure.
GLP compliance:
no
Remarks:
predating GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylamine
EC Number:
200-834-7
EC Name:
Ethylamine
Cas Number:
75-04-7
Molecular formula:
C2H5NH2
IUPAC Name:
ethanamine
Details on test material:
- Name of test material (as cited in study report): Ethylamine
- Analytical purity: no data
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Purity: approx. 100%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Mura: SPRA (SPF 68 Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: MUS Rattus, Brunnthal (Germany)
- Weight at study initiation: mean 185 ± 15
- Fasting period before study: None
- Diet: Herilan MRH, Eggersmann KG, Rinteln/Weser, Germany; ad libitum
- Water: Tap water; ad libitum

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body inhalation system
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: Caged in groups of 5
- Source and rate of air: 3000 L air/h
- Method of conditioning air: Gas bottle combined with a regulating valve and a mixing chamber to mix fresh air and gaseous test item
- Pressure in air chamber: Approx. - 10 Pa

TEST ATMOSPHERE
- Brief description of analytical method used: Test substance concentrations were analytically measured by determining the total organic carbon concentration using a calibrated flame ionization
- Samples taken from breathing zone: Yes

- Rationale for the selection of the starting concentration: An estimated concentration based on experiences with a inhalation risk test was chosen. One dosage allowed the calculation of a no effect level (LC0).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
0.9 L/h were analysed
Duration of exposure:
4 h
Remarks on duration:
By using the Haber's law the LC50 after 1h exposure duration was calculated
Concentrations:
Dose group 1: 1.15 mg/L (622 ppm)
Dose group 2: 5.45 mg/L (2954 ppm)
Dose group 3: 6.85 mg/L (3714 ppm)
Dose group 4: 7.52 mg/L (4105 ppm)
Dose group 5: 8.21 mg/L (4453 ppm)
Dose group 6: 11.58 mg/ L (6255 ppm)


The analyzed concentrations in the 1st test were 1150, 5450, and 8210 mg/m3 and in the 2nd test 6850, 7520 and 11580 mg/m³.
No. of animals per sex per dose:
10 males and 10 females per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Daily for clinical signs and mortality; Body weights were measured prior to, and then 7 and 14 days after exposure to the test substance
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, mortality, mean body weight per dose group
Statistics:
- Probit analysis
- The LC50 values for 1 hour exposure duration were calculated by using the Haber's law C x t = k

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
12.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
9.8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
8.1 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Mortality was observed for the dose groups 2, 5 and 6 (5.45 mg/L, 8.21 mg/L, 11.58 mg/L). The animals died within the period of the 4h treatment until day 9 after exposure.
For detailed information see Table 1 in "Any other information on results incl. tables"
Clinical signs:
other: Clinical symptoms were grooming, eye closure, corrosive effects to nose (red discharge), eye lid and cornea (blurred), swollen eyes, dyspnea, gasping and apathy, scrubby coat, salivation, tiptoeing and staggering gait. Clinical symptoms were observed for
Body weight:
Treatment related effects on the bodyweight gain were observed. After 7 days of observation male and female rats of the dose groups 2 to 6 gained apparently less weight compared to untreated control rats.
For detailed information see Table 2 in "Any other information on rsults incl. tables"


After 7 days men bodyweight development was positive in the control group, the low dose group, and the 7520 dose group. Except the 8210 mg/m³ dose group Mean body weight development was positive after 14 days.
Gross pathology:
Deceased animals:
- Pathological findings especially at the heart and lung
- Observations: Gas swolen bowel, distended lungs, hyperemia of the lung, lung edema, heart dilatation and hyperemia

Survivors: Organs without findings

Any other information on results incl. tables

Table 1: Mortality after 14 d for male and female rats

Exposure concentration [mg/L]

Mortality

Males

Mortality

Females

Mortality

Males/Females

Mortality

Males/Females [%]

1.15

0/10

0/10

0/20

0

5.45

2/10

1/10

3/20

15

6.85

0/10

0/10

0/20

0

7.52

0/10

0/10

0/20

0

8.21

10/10

7/10

17/20

85

11.58

5/10

1/10

6/20

30

Table 2: Mean body weight gain for male and female rats after 7 d and 14 d post-exposure period

Exposure concentration [mg/L]

Mean body weight gain after 7 d [g]

Mean body weight gain after 14 d [g]

Male

Female

Male

Female

Control

+ 40

+ 17

+ 72

+ 29

1.15

+ 32

+ 12

+ 62

+ 25

5.45

- 8

- 11

+ 40

+ 9

6.85

- 3

- 4

+ 46

+ 21

7.52

+ 10

+ 8

+ 59

+ 21

8.21

/

- 29

/

- 5

11.58

- 19

- 10

+ 29

+ 19

 

 

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the available study results, the test item provokes inhalative toxic effects after a 4 hour gas exposure period in rats. The mean lethal concentration was calculated to be 8.1 mg/L for females, 9.8 mg/L for males and 12.1 mg/L for male and female rats.
Executive summary:

Acute inhalation toxicity was analyzed in a study performed similar to OECD Guideline 403. Wistar rats were dosed with 1.15; 5.45; 6.85; 7.52; 8.21; and 11.58 mg/L of gaseous test item. After a 4 h exposure mortality was observed for the dose groups 5.45 mg/L, 8.21 mg/L and 11.58 mg/L amounting 15%, 85% and 30%, respectively. Based on this observations a LC50 of 9.8 mg/L air for males and 8.1 mg/L air for females and a combined LC50 of 12.6 mg/L air was calculated. Main clinical signs observed were eye closure, corrosive effects to nose (red discharge) and cornea (blurred), swollen eyes, dyspnea and apathy, scrubby coat, salivation, tip-toeing and staggering gait. With the exeption of the 1.15 mg/L exposure scenario clinical symptoms were observed until the end of the 14 d observation period. At necropsy, a gas swolen bowel, distended lungs, hyperemia of the lung, lung edema, heart dilatation and hyperemia were observed. Based on the most sensitive LC50 for females of 8.1 mg/L (equivalent to 4320 ppmV) the test substance can be categorized for inahalative toxicity cat. 4 based on GHS criteria.