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Acute Toxicity: oral

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Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
03 August 2010 to 24 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Available data from Etheramine C13i are considered to be applicable for C10i-etheramine as well. The structure of Etheramine C13i only differs from that of Etheramine C10i, in that the alkyl chain is only 2 carbons longer. This only has limited effects on physical properties, whereas chemical behaviour, reactivity and metabolism are the same. With alkylamines in general, the corrosive properties tend to increase with shortening of the alkyl chain. Therefore the results obtained from Etheramine C13i are therefore also expected to be of similar severity for Etheramine C10i. (See for more information endpoint summary Ch.7.1 Toxicokinetics)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reference
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:
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).
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.
Body weight:
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.
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(isotridecyloxy)propylamine
EC Number:
256-881-9
EC Name:
3-(isotridecyloxy)propylamine
Cas Number:
50977-10-1
Molecular formula:
C16H35NO
IUPAC Name:
3-[(11-methyldodecyl)oxy]propan-1-amine
Details on test material:
- Name of test material (as cited in study report): 3-(Isotridecyloxy)-1-propane amine
- Chemical name (IUPAC): 3-[(11-methyldodecyl)oxy]propan-1-amine
- Substance type: Clear colourless liquid
- Physical state: liquid
- Analytical purity: 95.8% m/m (NMR)
- Lot/batch No.: S001287
- Expiration date of the lot/batch: 30 April 2018
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Density: 840 kg/m3
- pH: 11

Test animals

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

Administration / exposure

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).

Results and discussion

Effect levels
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:
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).
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.
Body weight:
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.
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).

Applicant's summary and conclusion

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.