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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Repeated dose toxicity: 
oral: no data available
dermal: no data available
inhalation: 24 week inhalation: NOAEC: 100 ppm (184 mg/m3)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
1. The measured atmospheric concentrations are not reported. 2. No ophthalmological examinations were performed. 3. Food consumption was not measured. 4. It is not reported how many nasal sections were examined histopathologically.
Qualifier:
no guideline followed
Principles of method if other than guideline:
not specified
GLP compliance:
no
Species:
rat
Strain:
Fischer 344
Remarks:
CDF (F-344)/Crl BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Weight at study initiation:
- Males: 262 +/- 5 g
- Females: 159 +/- 3 g
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
- Exposure period: 6 h/day, 5 days/week for 24 weeks
- Route of administration: inhalation (whole body)
- Doses: 0, 18, 184 and 922 mg/m3
- Air changes: 12-15/hour
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
- Method: Wilks-Miran infrared analyzer
- Sampling times: 2-4 times per hour
Duration of treatment / exposure:
24 weeks
Frequency of treatment:
6 hours/day, 5 days/week
Dose / conc.:
10 ppm
Remarks:
equivalent to 18 mg/m3
Dose / conc.:
100 ppm
Remarks:
equivalent to 184 mg/m3
Dose / conc.:
500 ppm
Remarks:
equivalent to 922 mg/m3
No. of animals per sex per dose:
- Number of animals: 30/sex/treatment
Control animals:
yes
Observations and examinations performed and frequency:
- Clinical signs and mortality: twice daily
- Body weight: on the day preceding the first exposure and at 2-week intervals throughout the study period
- Haematology (on 10/sex/treatment only at terminal sacrifice): hemoglobin, hematocrit and complete and differential blood count
- Biochemistry (at 30 day and terminal sacrifice): alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, blood urea nitrogen, creatinine and sorbitol dehydrogenase
- Post-exposure period: No

- Examinations were performed on 6 animals/sex/treatment after 30 and 60 days of exposure and 12-18/sex/treatment at terminal sacrifice. These animals were necropsied and the following analyses were performed:
- Organ weights: lungs, liver, kidney and heart
- Macroscopic: complete gross necropsy
- Microscopic: lungs, liver, kidneys, heart, aorta, spleen, pancreas, tracheobronchial lymph nodes, mesenteric lymph nodes, adrenals, testes, seminal vesicles, ovaries, uterus, trachea, eye, bone marrow (sternum), thymus and nares (at terminal sacrifice only)
Other examinations:
Electrocardiograms of 10 anesthetized rats at terminal sacrifice.
Statistics:
Multiple t-tests, multivariate ANOVA, Kruskal-Wallis test and Chi-square test
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm rats kept their eyes closed and burried their noses in their fur during the entire exposure period
Mortality:
mortality observed, treatment-related
Description (incidence):
- one male and one female at 500 ppm
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
- significantly reduced at 500 ppm for both males and females
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm significantly increased relative weights of lung, kidney and heart for both males and females, probably due to the decreased body weights seen at this exposure level
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm moderate to marked atrophic rhinitis (16/16 male; 17/17 female) in the nasal passages, principally in the anterior half and characterized by: purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium

- at 500 ppm 1/16 male showed thymus athrophy (grade 4)

Other effects:
effects observed, treatment-related
Description (incidence and severity):
- no consistent treatment-related effects were seen in electrocardiography, although the QT-interval of male rats at 500 ppm was significantly longer than controls
Dose descriptor:
NOAEC
Effect level:
100 ppm
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 184 mg/m3
Dose descriptor:
LOAEC
Effect level:
500 ppm
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 922 mg/m3
Critical effects observed:
not specified
Conclusions:
NOAEC = 100 ppm (equivalent to 184 mg/m3) based on decreased body weights and histopathological changes of the nasal passages at 500 ppm.
Executive summary:

Fischer rats were exposed to 10, 100 and 500 ppm (18, 184, and 922 mg/m3) test substance for 24 weeks/120 days. The animals of the high dose group kept their eyes closed and buried their noses in their fur during the entire exposure period. Significantly increased relative weights of lung, kidney and heart for both males and females were seen at necropsy at this exposure level, probably due to the decreased body weights. Moderate to marked atrophic rhinitis in the nasal passages in 16/16 male and 17/17 female rats, principally in the anterior half and characterized by purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium, were observed at histopathology for the high dose group. The NOAEC for this second study was 100 ppm (184 mg/m3; local effects) based on the irritating effects of the test substance in the respiratory tract and the subsequent body/organs weight changes.

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
1. Publication is well documented and basic data are given. 2. No information was provided on the time of death of the animals. 3. Although actual concentrations were measured, no results are given. 4. It is not specified whether the histological examination included several nasal and laryngeal sections.
Qualifier:
no guideline followed
Principles of method if other than guideline:
not specified
GLP compliance:
no
Species:
rat
Strain:
Fischer 344
Remarks:
CDF (F-344)/Crl BR
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 days (over a 14-16 days period)
Frequency of treatment:
6 h/d
Dose / conc.:
250 ppm
Remarks:
equivalent to 460 mg/m3
Dose / conc.:
1 000 ppm
Remarks:
equivalent to 1840 mg/m3
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
- Post-exposure period: one day
Observations and examinations performed and frequency:
OBSERVATIONS AND FREQUENCY:
- Clinical signs: twice daily
- Mortality: twice daily
- Body weight: daily
- Histopathology of lungs, liver, kidney, heart, aorta, spleen, pancreas, tracheobronchial lymph nodes, adrenals, testes, epididymides, ovaries, uterus, trachea, and nares.
Statistics:
ANOVA, analysis of covariance, Fisher's exact test.
Mortality:
no mortality observed
Description (incidence):
No mortality observed at both high and low dose group (consisting of 5 male and 5 female rats).
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight was significantly decreased at the high dose group in males (~50% decrease) and females (~36% decrease).
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
At 250 ppm slight and moderate necrotizing inflammation of the nasal cavity in 3/5 males (sections for females were not available for examination).
At 1000 ppm above-mentioned lesion in 5/5 males (sections for females were not available for examination).
Moderate thymic atrophy in all males and females.
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
250 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: body weight
Remarks on result:
other: equivalent to 460 mg/m3
Dose descriptor:
LOAEC
Remarks:
local
Effect level:
250 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 460 mg/m3
Critical effects observed:
not specified
Conclusions:
NOAEC (systemic) and LOAEL (local) was 250 ppm equivalent to a dose of 460 mg/m3.
Executive summary:

A 10-day inhalative toxicity study was performed on Fischer 344 rats (5 rats/sex/dose group) exposed to 250 ppm and 1000 ppm for 6h/day on 10 days over a 14 to 16 days period. No mortality was observed at both high and low dose groups. The exposure to 250 and 1000 ppm of the test item resulted in slight and moderate necrotizing inflammation of the nasal cavity. In addition, moderate thymic atrophy was found in rats exposed to 1000 ppm of the test substance. 250 ppm (460 mg/m3) was the LOAEC for respiratory tract irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
184 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
1. The measured atmospheric concentrations are not reported. 2. No ophthalmological examinations were performed. 3. Food consumption was not measured. 4. It is not reported how many nasal sections were examined histopathologically.
Qualifier:
no guideline followed
Principles of method if other than guideline:
not specified
GLP compliance:
no
Species:
rat
Strain:
Fischer 344
Remarks:
CDF (F-344)/Crl BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Weight at study initiation:
- Males: 262 +/- 5 g
- Females: 159 +/- 3 g
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
- Exposure period: 6 h/day, 5 days/week for 24 weeks
- Route of administration: inhalation (whole body)
- Doses: 0, 18, 184 and 922 mg/m3
- Air changes: 12-15/hour
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
- Method: Wilks-Miran infrared analyzer
- Sampling times: 2-4 times per hour
Duration of treatment / exposure:
24 weeks
Frequency of treatment:
6 hours/day, 5 days/week
Dose / conc.:
10 ppm
Remarks:
equivalent to 18 mg/m3
Dose / conc.:
100 ppm
Remarks:
equivalent to 184 mg/m3
Dose / conc.:
500 ppm
Remarks:
equivalent to 922 mg/m3
No. of animals per sex per dose:
- Number of animals: 30/sex/treatment
Control animals:
yes
Observations and examinations performed and frequency:
- Clinical signs and mortality: twice daily
- Body weight: on the day preceding the first exposure and at 2-week intervals throughout the study period
- Haematology (on 10/sex/treatment only at terminal sacrifice): hemoglobin, hematocrit and complete and differential blood count
- Biochemistry (at 30 day and terminal sacrifice): alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, blood urea nitrogen, creatinine and sorbitol dehydrogenase
- Post-exposure period: No

- Examinations were performed on 6 animals/sex/treatment after 30 and 60 days of exposure and 12-18/sex/treatment at terminal sacrifice. These animals were necropsied and the following analyses were performed:
- Organ weights: lungs, liver, kidney and heart
- Macroscopic: complete gross necropsy
- Microscopic: lungs, liver, kidneys, heart, aorta, spleen, pancreas, tracheobronchial lymph nodes, mesenteric lymph nodes, adrenals, testes, seminal vesicles, ovaries, uterus, trachea, eye, bone marrow (sternum), thymus and nares (at terminal sacrifice only)
Other examinations:
Electrocardiograms of 10 anesthetized rats at terminal sacrifice.
Statistics:
Multiple t-tests, multivariate ANOVA, Kruskal-Wallis test and Chi-square test
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm rats kept their eyes closed and burried their noses in their fur during the entire exposure period
Mortality:
mortality observed, treatment-related
Description (incidence):
- one male and one female at 500 ppm
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
- significantly reduced at 500 ppm for both males and females
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm significantly increased relative weights of lung, kidney and heart for both males and females, probably due to the decreased body weights seen at this exposure level
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
- at 500 ppm moderate to marked atrophic rhinitis (16/16 male; 17/17 female) in the nasal passages, principally in the anterior half and characterized by: purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium

- at 500 ppm 1/16 male showed thymus athrophy (grade 4)

Other effects:
effects observed, treatment-related
Description (incidence and severity):
- no consistent treatment-related effects were seen in electrocardiography, although the QT-interval of male rats at 500 ppm was significantly longer than controls
Dose descriptor:
NOAEC
Effect level:
100 ppm
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 184 mg/m3
Dose descriptor:
LOAEC
Effect level:
500 ppm
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 922 mg/m3
Critical effects observed:
not specified
Conclusions:
NOAEC = 100 ppm (equivalent to 184 mg/m3) based on decreased body weights and histopathological changes of the nasal passages at 500 ppm.
Executive summary:

Fischer rats were exposed to 10, 100 and 500 ppm (18, 184, and 922 mg/m3) test substance for 24 weeks/120 days. The animals of the high dose group kept their eyes closed and buried their noses in their fur during the entire exposure period. Significantly increased relative weights of lung, kidney and heart for both males and females were seen at necropsy at this exposure level, probably due to the decreased body weights. Moderate to marked atrophic rhinitis in the nasal passages in 16/16 male and 17/17 female rats, principally in the anterior half and characterized by purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium, were observed at histopathology for the high dose group. The NOAEC for this second study was 100 ppm (184 mg/m3; local effects) based on the irritating effects of the test substance in the respiratory tract and the subsequent body/organs weight changes.

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
1. Publication is well documented and basic data are given. 2. No information was provided on the time of death of the animals. 3. Although actual concentrations were measured, no results are given. 4. It is not specified whether the histological examination included several nasal and laryngeal sections.
Qualifier:
no guideline followed
Principles of method if other than guideline:
not specified
GLP compliance:
no
Species:
rat
Strain:
Fischer 344
Remarks:
CDF (F-344)/Crl BR
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 days (over a 14-16 days period)
Frequency of treatment:
6 h/d
Dose / conc.:
250 ppm
Remarks:
equivalent to 460 mg/m3
Dose / conc.:
1 000 ppm
Remarks:
equivalent to 1840 mg/m3
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
- Post-exposure period: one day
Observations and examinations performed and frequency:
OBSERVATIONS AND FREQUENCY:
- Clinical signs: twice daily
- Mortality: twice daily
- Body weight: daily
- Histopathology of lungs, liver, kidney, heart, aorta, spleen, pancreas, tracheobronchial lymph nodes, adrenals, testes, epididymides, ovaries, uterus, trachea, and nares.
Statistics:
ANOVA, analysis of covariance, Fisher's exact test.
Mortality:
no mortality observed
Description (incidence):
No mortality observed at both high and low dose group (consisting of 5 male and 5 female rats).
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight was significantly decreased at the high dose group in males (~50% decrease) and females (~36% decrease).
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
At 250 ppm slight and moderate necrotizing inflammation of the nasal cavity in 3/5 males (sections for females were not available for examination).
At 1000 ppm above-mentioned lesion in 5/5 males (sections for females were not available for examination).
Moderate thymic atrophy in all males and females.
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
250 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: body weight
Remarks on result:
other: equivalent to 460 mg/m3
Dose descriptor:
LOAEC
Remarks:
local
Effect level:
250 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic
Remarks on result:
other: equivalent to 460 mg/m3
Critical effects observed:
not specified
Conclusions:
NOAEC (systemic) and LOAEL (local) was 250 ppm equivalent to a dose of 460 mg/m3.
Executive summary:

A 10-day inhalative toxicity study was performed on Fischer 344 rats (5 rats/sex/dose group) exposed to 250 ppm and 1000 ppm for 6h/day on 10 days over a 14 to 16 days period. No mortality was observed at both high and low dose groups. The exposure to 250 and 1000 ppm of the test item resulted in slight and moderate necrotizing inflammation of the nasal cavity. In addition, moderate thymic atrophy was found in rats exposed to 1000 ppm of the test substance. 250 ppm (460 mg/m3) was the LOAEC for respiratory tract irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
184 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

No data for the evaluation of the oral repeated dose toxicity available.

 

Dermal:

No data for the evaluation of the dermal repeated dose toxicity available.

Inhalation:

A 10-day inhalation toxicity study (Virginia Chem, 1984; reliability score: 2) was performed on Fischer 344 rats (5 rats/sex/dose group) exposed to 250 ppm or 1000 ppm for 6h/day on 10 days over a 14 to 16 days period. No mortality was observed at both high and low dose groups. The exposure to 250 and 1000 ppm of the test item resulted in slight and moderate necrotizing inflammation of the nasal cavity. In addition, moderate thymic atrophy was found in rats exposed to 1000 ppm of the test substance. 250 ppm (460 mg/m3) was the LOAEC for respiratory tract irritation

In a second study (Virginia Chem, 1984; reliability score: 2), Fischer rats were exposed to 10, 100, or 500 ppm (18, 184, or 922 mg/m3) test substance for 24 weeks (=120 days). The animals of the high dose group kept their eyes closed and buried their noses in their fur during the entire exposure period. Significantly increased relative weights of lung, kidney and heart for both males and females were seen at necropsy at this exposure level, probably due to the decreased body weights. Moderate to marked atrophic rhinitis in the nasal passages in 16/16 male and 17/17 female rats, principally in the anterior half and characterized by purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium, were observed at histopathology for the high dose group. The NOAEC for this study was 100 ppm (184 mg/m3) based on the irritating effects of the test substance in the respiratory tract and the subsequent body/organs weight changes.

There are further studies in rats and rabbits available, based on very poor documentation the studies are disregarded and not considered for hazard assessment of ethylamine.

Justification for classification or non-classification

Based on the available data ethylamine does not need to be classified for repeated dose toxicity according to Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.