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Administrative data

Description of key information

Acute Toxicity:
- oral: LD50 = 400 mg/kg bw
- inhalation: LC50 = 4320 ppmV = 8.1 mg/L

- dermal: LD50 = 265 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other:
Remarks:
Acceptable publication but only limited data is given.
Qualifier:
no guideline available
Principles of method if other than guideline:
Principle of test:
Single oral dose toxicity is estimated by the gastric intubation of groups of five non-fasted Carworth-Wistar rats, weighing 90 to 120 grams and maintained from time of weaning on Rockland rat diet, complete. The most probable LD50 value and its fiducial range were estimated by the method of Thompson.
GLP compliance:
no
Remarks:
predating GLP
Limit test:
no
Specific details on test material used for the study:
FORM AS APPLIED IN THE TEST: Aqueous solution
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 90 to 120 grams
- Diet: Rockland rat diet

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1 to 10 mL

Doses:
No data; dosages were in a logartitmic series
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
not specified
Dose descriptor:
LD50
Effect level:
400 mg/kg bw
Based on:
test mat.
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The mean lethal dose of the test substance after single oral administration was found to be 400 mg/kg bw in rats.
Executive summary:

The test article was administered to a group of 5 non-fasted Carworth-Wistar rats by intubation of dosages in a logartithmic series. After 14 days of observation the single dose oral toxicity was calculated to be 400 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
400 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
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
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Purity: approx. 100%

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
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
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

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

 

 

 
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
8 100 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Acceptable publication but only limited data is given.
Principles of method if other than guideline:
- Principle of the test: According to Draize, J.H. et al.: J. Pharmacol. and Exper. Therap. 82:377, 1944
- Short description of test conditions: Penetration of rabbit skin was estimated by a technique closely skin to the one-day cuff method of Draize and associates, using groups of four male. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period.
GLP compliance:
no
Remarks:
predating GLP
Species:
rabbit
Strain:
New Zealand White
Remarks:
giant
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 to 3.5 kg
Type of coverage:
occlusive
Vehicle:
not specified
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
4
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
265 mg/kg bw
95% CL:
201 - 395
Remarks on result:
other: original value LD50 = 0.39 ml/kg
Mortality:
no data
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The mean lethal dose of the test substance after single dermal application for 24 hours was found to be 265 mg/kg bw in rabbits.
Executive summary:

Penetration of rabbit skin with the test article was estimated by a technique closely skin to the one-day cuff method of Draize and associates (Draize et al. 1944), using groups of four male New Zealand giant albino rabbits. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period. Based on the study results a LD50 of 265 mg/kg/bw was calculated.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
265 mg/kg bw

Additional information

Oral:

In the key study (Smyth et al., 1954; reliabilty score: 2), the test article was administered to a group of 5 non-fasted Carworth-Wistar rats by intubation of dosages in a logartithmic series. After 14 days of observation the single dose oral toxicity was calculated to be 400 mg/kg bw.

In another study (Union Carbide Corp, 1953; reliabilty score: 2), the test article was fed as a 2% solution of the test material (71.8% solution) to a group of 5 non-fasted Carworth Wistar rats by intubation of dosages differing by a factor of two. All animals died within 5 minutes after administration of 2000 mg/kg bw of the test item. At autopsy lungs were congested, livers mottled, kidneys congested and there was an extreme irritation of the gastrointestinal tract with contents bloody and walls opaque because of corrosive action. After 14 days of observation the single dose oral toxicity was calculated to be 390 mg/kg bw.

Inhalation:

Acute inhalation toxicity was analyzed in a key study (BASF, 1979) performed similar to OECD TG 403 (reliability score: 2). Wistar rats were dosed with 1.15; 5.45; 6.85; 7.52; 8.21; and 11.58 mg/L of the 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.

In a study performed similar to OECD TG 403 ( Air Products and Chemicals, Inc., 1993), the inhalation toxicity of the test substance as a gas after exposure of male and female albino rats for 6, 20 and 60 minutes at various concentrations (in total 18 test groups). Animals were maintained for a 14-day observation period and examined for mortality, body weight changes and clinical signs. Based on the mortality data for the different exposure times LC50 values could be determined, amounting to 22200 ppm, 9136 ppm and 5540 ppm for exposure times of 6 min, 20 min and 60 min, respectively. Significant pharmacotoxic signs were corneal opacity, labored breathing, rales and gasping. At necropsy the macroscopic abnormalities constisted of eye abnormalities (cloudy and white corneas) and congested lungs.

In an inhalation risk test (BASF, 1978; reilability score: 2) was performed with male and female Sprague-Dawley rats and a saturated vapour concentration of 1.8 g/L test substance (calculated value). The vapour-air-mixture was prepared by passing dried air (air flow 200 L/h) through a 70% solution of the test item of 5 cm hight at 20 °C. The scheduled exposure time was 3 min, 10 min, 30 min, 1 h, 3 h, 7 h. Post exposure observation period was planned to be 14 days. Mortality, clinical symptoms and macroscopic effects seen at necropsy were recorded. After 3 min of exposure all animals died. Clinical symptoms at exposure were violent attempts to escape, eye closure, grooming, corrosive effects to nose (bloody discharge; Ames positive) and cornea (blurred), dyspnea and cyanosis. Pathological examinantions revealed distended lungs, heart dilatation and reactive hyperemia.

In an additional inhalation toxicity assessment according to EPA OPP 81 -3 (Pennwalt Corporation, 1986; reliability score: 2), Sprague-Dawley derived rats recieved a single four-hour exposure to 2580 ppm test item. All animals survived to termination (LC0 = 4.75 mg/L). Signs of treatment were observed during expsoure until the end of the 14 day post-exposure period and included increased secretory responses, respiratory distress, hunched appearance, closed eyes, matted coat, reduced activity, pallor, discolored ano-genital area and corneal irregularities. A minimal, transient adverse effect upon body weight was produced by treatment. Gross postmortem observations were considered unremarkable.

Dermal:

In the key study (Smyth et al., 1954; reliability score: 2), penetration of rabbit skin with the test article was estimated by a technique similar to the one-day cuff method of Draize and associates (Draize et al. 1944), using groups of four male New Zealand giant albino rabbits. The fur was removed from the entire trunk by clipping, and the dose was retained beneath an impervious plastic film. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period. Based on the study results a LD50 of 265 mg/kg/bw was calculated.

In addition, in a range-finding study the clipped skin of the trunk of four male albino New Zealand rabbits was exposed with the undiluted test item. The animals were immobilized during the 24 hour contact period, after which the film was removed and the rabbits were caged for the subsequent 14 day observation period. Based on the mortality data a LD50 of 360 mg/kg bw was calculated. The treatment caused necrosis of the skin and formation of a leathery scab, characteristic of amine burns. Lungs of those dying were congested or hemorrhaged. All organs that were in contact with the peritoneal wall were burned by this compound.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A LD50 value of 400 mg/kg bw after oral intake, LC50 value of 4320 ppmV (= 8100 mg/m³) after inhalation exposure, and a LD50 value of 265 mg/kg bw after dermal application were identified.

Ethylamine (aqueous solution)

The substance in aqueous solution is considered to be classified for acute oral cat. 4, acute inhalation toxicity cat. 4, and acute dermal toxicity cat. 3 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.

Ethylamine (gas)

The substance is considered to be classified for acute inhalation toxicity cat. 4 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.

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