Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The oral LD50 of all Etheramines at similar chain lengths is within the range of 300-2000 mg/kg bw, with LD50 cut-off value of 500 mg/kg body weight. There is no data available on acute toxicity via inhalation or dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
January 15, 1985 - January 30, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Limited reporting. - 3 dose levels: 25, 200 and 2000 mg/kg - 4 animals: 2 M + 2 F at each dose level - animals aging 4 to 6 weeks
GLP compliance:
yes
Remarks:
audited inhouse
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley obtained from Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks of age
- Weight at study initiation: 100 to 136 g
- Fasting period before study: overnight and approximately 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet (Scientific Feeds LAD 1 obtained from Special Diet Services Ltd., Witham, Essex, England),
ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period:minimum period of 5 days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): min 21 + max 23
- Humidity (%): average 42%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period


IN-LIFE DATES: From: 15 January 1985 To: 30 January 1985
Route of administration:
oral: gavage
Vehicle:
other: water, and the other one is unknown (supplied by Sponsor)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 concentrations tested: one as supplied bij Sponsor (unknown vehicle) and one as 25% w/v solution in distilled water
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: no justification, but it is in contrast with info about the insolubility of substance in water and solubility in acetone
- Lot/batch no. (if required): no info
- Purity: no info


MAXIMUM DOSE VOLUME APPLIED: 2.4 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no info, just started with lowest dose level
Doses:
Dose levels:
- 25 mg/kg
- 200 mg/kg
- 2000 mg/kg
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations after dosing, frequently on Day 1 and on subsequent days twice per day. Weighing on Days 1 (dosing), 4, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (macroscopic post mortem examination)
Statistics:
No statistics.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Remarks on result:
other: No confidence limits
Mortality:
At 2000 mg/kg all animals died (2 males and 2 females).
Clinical signs:
other: - 25, 200 and 2000 mg/kg: pilo-erection, abnormal body carriage (hunched posture) and increased salivation (shortly after dosing) - 200 and 2000 mg/kg: abnormal gait (waddling), lethargy, decreased respiratory rate and pallor of the extremities - 200 mg/k
Gross pathology:
- Animals that died: Autopsy revealed congestion or haemorrhage of the lungs, pallor of the liver and kidneys and haemorrhage of the stomach
blood vessels.
- Terminal autopsy findings were normal.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute lethal oral dose to rats of Etheramine C8-10 was found to be: between 200 and 2000 mg/kg bodyweight, with a LD50 cut-off of 500 mg/kgbw.
Executive summary:

The study was performed with similarities to OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method) and according to GLP standards (audited in-house).

The test material, Etheramine C8-10 was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 25, 200 and 2000 mg/kg to two males and two females. Dosing started with the lowest dose. As no deaths occurred at this level within 24 hours, the next dose was given to another group, and so on. At the 2000 mg/kg level all four animals died. Clinical signs of toxicity included pilo-erection, hunched posture and increased salivation accompanied by lethargy, abnormal gait, decreased respiratory rate and pallor of the extremities. Gross pathologic examination on the animals that died showed congestion or haemorrhage of the lungs, pallor of the liver and kidneys and haemorrhage of the stomach blood vessels. Gross pathologic examination at termination revealed nothing remarkable.

Conclusion: The acute oral LD50 of Etheramine 810 for rats is between 200 and 2000 mg/kg of body weight. Confidence limits could not be calculated.

The etheramine is (very) corrosive. The test substance was administrated undiluted at 200 and 2000 mg/kg with 0.24 ml/kg resp. 2.4 ml/kg. Autopsy of the animals that died from 2.4 ml/kg, showed haemorrhage of the stomach. At 0.24 ml/kg the undiluted substance was likely to be just as corrosive locally, however, the volume dose was not sufficient to cause the death of the animals, and they fully recovered. It is uncertain what would happen at 300 mg/kg when 0.36 ml/kg would be dosed, but it is expected that most of the animals would survive this.

Consequently, Etheramine C8-10 is classified for GHS as Toxicity Category 4 with LD50 cut-off of 500 mg/kgbw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
January 15, 1985 - January 30, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Limited reporting. - 4 dose levels, highest is exceptionally: 25, 200, 2000 and 5000 mg/kg - 4 animals: 2 M + 2 F at each dose level - animals aging 4 to 6 weeks
GLP compliance:
yes
Remarks:
audited inhouse
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley obtained from Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks of age
- Weight at study initiation: 100 to 133 g
- Fasting period before study: overnight and approximately 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet (Scientific Feeds LAD 1 obtained from Special Diet Services Ltd., Witham, Essex, England),
ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period:minimum period of 5 days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): min 21 + max 23
- Humidity (%): average 42%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period


IN-LIFE DATES: From: 15 January 1985 To: 30 January 1985
Route of administration:
oral: gavage
Vehicle:
other: corn oil, and the other one is unknown (supplied by Sponsor)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 concentrations tested: one as supplied bij Sponsor (unknown vehicle) and one as 25% w/v solution in distilled water
- Amount of vehicle (if gavage): no info
- Justification for choice of vehicle: no justification, but the substance is insoluble in water and soluble in acetone
- Lot/batch no. (if required): no info
- Purity: no info


MAXIMUM DOSE VOLUME APPLIED: 5.75 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no info, just started with lowest dose level
Doses:
Dose levels:
- 25 mg/kg
- 200 mg/kg
- 2000 mg/kg
- 5000 mg/kg
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations after dosing, frequently on Day 1 and on subsequent days at least twice per day. Weighing
on Days 1 (dosing), 4, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (macroscopic post mortem examination)
Statistics:
No statistics.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Remarks on result:
other: No confidence limits
Mortality:
At 2000 mg/kg and 5000 mg/kg all animals died (4 males and 4 females).
Clinical signs:
other: - 25, 200, 2000 and 5000 mg/kg: pilo-erection, abnormal body carriage (hunched posture) and increased salivation (shortly after dosing) - 200, 2000 and 5000 mg/kg: abnormal gait (waddling), lethargy and pallor of the extremities - 2000 and 5000 mg/kg: dec
Gross pathology:
- Animals that died: autopsy revealed haemorrhage and congestion of the lungs and pallor of the spleen, liver and kidneys
- Terminal autopsy findings were normal.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute lethal oral dose to rats of Etheramine C12-15 was found to be: between 200 and 2000 mg/kg bodyweight, with a LD50 cut-off of 500 mg/kgbw.
Executive summary:

The study was performed with similarities to OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method) and according to GLP standards (audited in-house).

The test material, Etheramine C12-15 was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 25, 200, 2000 and 5000 mg/kg to two males and two females. Dosing started with the lowest dose. As no deaths occurred at this level within 24 hours, the next dose was given to another group, and so on. At the 2000 and 5000 mg/kg levels all animals died. Clinical signs of toxicity included pilo-erection, abnormal body carriage and increased salivation accompanied by lethargy, abnormal gait, decreased respiratory rate, pallor of the extremities and ptosis. Gross pathologic examination on the animals that died showed haemorrhage and congestion of the lungs and pallor of the spleen, liver and kidneys. Gross pathologic examination at termination revealed nothing remarkable.

The dose of at 5000 mg/kg did not seem to results to higher toxicity compared to 2000 mg/kg, as time to death was not shorter (actually longer on average.)

The etheramine is (very) corrosive. The test substance was administrated undiluted at 200, 2000 and 5000 mg/kg with 0.23, 2.3 and 5.75 ml/kg respectively. It is uncertain what would happen at 300 mg/kg when 0.35 ml/kg would be dosed, but it is expected that most of the animals would survive this.

Consequently, Etheramine C12-15 is classified for GHS as Toxicity Category 4 with LD50 cut-off of 500 mg/kgbw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
January 15, 1985 - January 30, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Limited reporting. - 2 dose levels: 25 mg/kg + 200 mg/kg - 4 animals: 2 M + 2 F at each dose level - animals 4 to 6 weeks of age
GLP compliance:
yes
Remarks:
audited inhouse
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley obtained from Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks of age
- Weight at study initiation: 100 to 114 g
- Fasting period before study: overnight and approximately 4 hours after dosing
- Housing: metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet (Scientific Feeds LAD 1 obtained from Special Diet Services Ltd., Witham, Essex, England),
ad lib
- Water (e.g. ad libitum):ad lib
- Acclimation period:minimum period of 5 days prior to the start of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): min 21 + max 23
- Humidity (%): average 42%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period


IN-LIFE DATES: From: 15 January 1985 To: 30 January 1985
Route of administration:
oral: gavage
Vehicle:
other: water, and the other one is unknown (supplied by Sponsor)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 concentrations tested: one as supplied bij Sponsor (unknown vehicle) and one as 25% w/v solution in distilled water
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: no justification, but it is in contrast with info about the insolubility of the substance in water and solubility in
acetone
- Lot/batch no. (if required): no info
- Purity: no info


MAXIMUM DOSE VOLUME APPLIED: 0.24 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no info, just started with the lowest dose
Doses:
Dose levels:
- 25 mg/kg
- 200 mg/kg
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations after dosing, frequently on Day 1 and on subsequent days twice per day. Weighing on Days 1 (dosing), 4, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (macroscopic post mortem examination)
Statistics:
No statistics.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 200 mg/kg bw
Remarks on result:
other: No confidence limits
Mortality:
At 200 mg/kg 2 rats died (1 male and 1 female).
Clinical signs:
other: - 25 and 200 mg/kg: pilo-erection and increased salivation (shortly after dosing), abnormal body carriage (hunched posture) and abnormal gait (waddling) - 200 mg/kg: lethargy, pallor of the extremities and body tremors - Recovery as judged by external app
Gross pathology:
- Animals that died: Autopsy revealed congestion of the lungs, pallor of the liver, congestion of the stomach blood vessels and haemorrhage of the stomach amongst these animals. Body weight losses were recorded.
- Terminal autopsy findings were normal.
Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute lethal oral dose to rats of Etheramine 800 G was found to be: in the region of 200 mg/kg bodyweight.
Executive summary:

The study was performed with similarities to OECD Guideline 423 (Acute Oral Toxicity - acute Toxic Class Method) and according to GLP standards (audited inhouse).

The test material, Etheramine 800 G was evaluated for its acute oral toxicity potential in rats when administered as gavage doses at levels of 25 and 200 mg/kg to males and females. Dosing started with the lowest dose. As no deaths occured at this level within 24 hours, the next dose was given to another group. At the 200 mg/kg level 2 out of 4 animals died. Clinical signs of toxicity included pilo-erection and increased salivation accompanied by hunched posture and abnormal gait. Gross pathologic examination on the animals that died showed congestion of the lungs, pallor of the liver and congestion of the stomach blood vessels. Gross pathologic examination at termination revealed nothing remarkable.

Conclusion: The acute oral LD50 of Etheramine 800 G for rats is in the region of 200 mg/kg of body weight. Confidence limits could not be calculated.

According to GHS Etheramine 800 G is classified as Toxicity Category III.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
03 August 2010 to 24 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing
sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment
(Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest,
Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory
conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a
good state of health.
Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not
reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis
are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 21.5ºC
- Humidity (%): 46 - 79%
Temporary deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial
fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 03 August 2010 to 24 August 2010
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.

CLASS METHOD
- Rationale for the selection of the starting dose: Based on anticipated mortality at the next higher dose.
Doses:
300 mg/kg (0.36 mL/kg) body weight
2000 mg/kg (2.38 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / density (g/mL)
No. of animals per sex per dose:
300 mg/kg: 6 (2 groups of three females in a stepwise manner)
2000 mg/kg: 3
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 300 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test
substance. Water was available ad libitum.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead or sacrificed after Day 1).
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The
symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50
value).
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The incidence of mortality was as follows, presented in chronological order of treatment:
Dose level Mortality Sex Date of treatment
300 mg/kg 1/3 females 03 August 2010
300 mg/kg 0/3 females 10 August 2010
2000 mg/kg 3/3 females 17 August 2010

The decedents and moribund animals were found dead or sacrificed in moribund condition on Day 4 (300 mg/kg) or between days 2 and 3 post-treatment (2000 mg/kg).
Clinical signs:
other: Clinical signs observed during the study period were as follows: Dose level Clinical signs 300 mg/kg Hunched posture, piloerection, lethargy, labored respiration, rales, watery discharge from the eye, chromodacryorrhoea and/or salivation (all animals). 2
Gross pathology:
The following macroscopic post mortem findings were recorded:
Dose level Macroscopic findings
300 mg/kg : Cannibalism and irregular surface of the forestomach (female found dead).
2000 mg/kg : Gelatinous gastro-intestinal tract (one animal) or beginning stage of autolysis (one animal).
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The oral LD50 value of 3-(Isotridecyloxy)-1-propane amine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.
Executive summary:

The acute oral toxicity of 3-(Isotridecyloxy)-1-propane amine in the rat was studied according to the Acute Toxic Class Method.

Initially, 3-(Isotridecyloxy)-1-propane amine was administered by oral gavage to three female Wistar rats at 300 mg/kg body weight. In a stepwise procedure additional groups of females were dosed at 2000 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

The incidence of mortality was as follows, presented in chronological order of treatment:

300 mg/kg       1/3

300 mg/kg       0/3

2000 mg/kg     3/3

The decedents and moribund animals were found dead or sacrificed in moribund condition on Day 4 (300 mg/kg) or between days 2 and 3 post-treatment (2000 mg/kg).

Clinical signs observed during the study period were as follows:

300 mg/kg: Hunched posture, piloerection, lethargy, labored respiration, rales, watery discharge from the eye, chromodacryorrhoea and/or salivation (all animals).

2000 mg/kg: Restless behaviour, lethargy, hunched posture, uncoordinated movements, shallow respiration, piloerection, diarrhoea, salivation, chromodacryorrhoea, lean appearance and/or ptosis (all animals).

The surviving animals at 300 mg/kg had recovered from the symptoms by Day 6.

 

Weight loss was observed for the female at 300 mg/kg found dead on Day 4 and for two females at 2000 mg/kg found dead/sacrificed on Day 3. Surviving females at 300 mg/kg showed normal body weighty gain.

 

The following macroscopic post mortem findings were recorded:

300 mg/kg : Cannibalism and irregular surface of the forestomach (female found dead).

2000 mg/kg : Gelatinous gastro-intestinal tract (one animal) or beginning stage of autolysis (one animal).

 

The oral LD50 value of 3-(Isotridecyloxy)-1-propane amine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw
Quality of whole database:
All studies are guideline (OECD 423, ACT) studies performed under GLP. Cross-reading validity is high, as various similar structures all lead to similar results.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data is available on 3-((C9-11-iso,C10-rich)alkyloxy)propan-1-amine (further referred to as Etheramine C10i), but there is sufficient data available on vey similar products for an adequate evaluation.

 

Etheramine C13i was tested for acute oral toxicity according to acute toxic class method.

The incidence of mortality:

Dose level

Mortality (day)

Sex

Clinical signs

300 mg/kg

1/3 (4)

females

Hunched posture, piloerection, lethargy, laboured respiration, rales, watery discharge from the eye, chromodacryorrhoea and/or salivation (all animals). Full recovery day 6.

300 mg/kg

0/3

females

2000 mg/kg

3/3 (2-3)

females

Restless behaviour, lethargy, hunched posture, uncoordinated movements, shallow respiration, piloerection, diarrhoea, salivation, chromodacryorrhoea, lean appearance and/or ptosis (all animals).

 

The oral LD50 was established to be within the range ofmg/kg body weight, with LD50 cut-off value of 500 mg/kg body weight.

 

Available data from similar alkyl-etheramines show comparable results. They are all (very) corrosive substances. With alkylamines in general the corrosive properties tend to increase with shortening of the alkyl chain, which is also reflected in a generally observed tendency of higher acute oral toxicity.

Also in the case of the alkyl ether amines, the highest toxicity is observed for the Etheramine C8(branched), where the LD50 was determined at about 200 mg/kg based on the observed mortality of 2/4 animals at that dose level. In literature an acute oral LD50 for Etheramine C8(branched) of 310 mg/kg bw is reported. (Smyth HF, Carpenter CP, Weil CS, 1951, Range-finding toxicity data: List IV, A M A Arch Ind Hyg Occup Med 4(2), 119-22.)

 

Acute toxicity of comparable etheramines:

Substance

Alkyl chain

LD50 (mg/kgbw)

Etheramine C13i

branched C13

500 (between 300 -2000)

3-(C12-15-alkyl)oxypropylamine

C12-15

500 (between 200-2000)

3-octyl/decyloxypropylamine

C8 -10

500 (between 200-2000)

3-(2-ethylhexyl)oxypropylamine

branched C8

about 200; Lit: 320

 

From the above it is concluded that Etheramine C10i can be expected to lead to similar results when tested for acute oral toxicity, leading to a LD50 between 300-2000 mg/kg with LD50 cut-off of 500 mg/kg bw. Testing for acute oral toxicity with this corrosive substance is cannot be expected to contribute to better or different data and therefore scientifically not justified.

 

Support from QSAR (TOPKAT) supports the finding that LD50 increases with chain-length, but also that branching results to an (expected slight) increase of LD50 compared to linear alkyl chains. (See attached graph)

Acute dermal toxicity: Etheramine C10i is corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material. For corrosive substances, the use of protective gloves and other equipment, such as face shields, aprons and good work practices are mandatory. Consequently, the occurrence of substantial dermal exposure of amounts comparable to the levels for acute oral toxicity is unlikely.

 

Acute inhalation toxicity: The substance is classified as corrosive and no acute toxicity testing should normally be conducted. As the substance is corrosive, symptoms of local respiratory irritation are expected, which should limit the systemic uptake of amounts needed for systemic toxicity considering the relatively low acute oral toxicity.

Justification for classification or non-classification

The acute oral LD50 of Etheramine C10i can be expected to be within the range of 300-2000 mg/kg bw. Hence the product should be classified according to GHS for acute toxicity as Cat.4, with hazard statement H302: Harmful if swallowed.

Acute dermal testing with corrosive materials is not justified. As a consequence no classification can be made for acute dermal toxicity. Effects will be characterised by local tissue damage. Systemic uptake via skin is likely to be very limited.

No classification for acute dermal toxicity is therefore indicated.

 

Also for acute inhalation toxicity information for classification is lacking, and is testing not justified.