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Description of key information

The acute oral LD0 of N-(3-Aminopropyl)diethanolamine was found to be greater than 2,000 mg active ingredient/kg bodyweight in the Sprague-Dawley CD rats. The single dose acute dermal LD0 of N-(3-Aminopropyl)diethanolamine is greater than 2,000 mg/kg of body weight in male and female rats. No data is available for acute inhalation toxicity.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to the OECD guideline 401 and GLP compliant
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 214 to 230g (males); 202 to 230g (females)
- Fasting period before study: yes (overnight fast immediately before dosing and for approximately three to four hours after dosing)
- Housing: groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 51 to 62 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE - none
MAXIMUM DOSE VOLUME APPLIED: 2.14 ml/kg
Doses:
2268mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Range finding study
A range-finding study was performed to establish a dosing regime as follows: 1 male and 1 female were dosed with 2268 mg/kg of CA058 (equivalent to 2000 mg active ingredient/kg bodyweight). The 2 animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for five days.
lndividual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

Main study
- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days.
- Frequency of weighing: prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: behavioural and clinical observations, gross lesions.
Preliminary study:
There were no deaths.
Hunched posture was commonly noted four hours and up to five days after dosing.
Based on this information, a dose level of 2000 mg active ingredient/kg bodyweight was selected for the main study.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: There were no deaths at this dose level.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD0 of APDEA, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg active ingredient/kg bodyweight.
Executive summary:

The study was performed to assess the acute oral toxicity of N-(3-Aminopropyl)diethanolamine in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987), Method 81 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC) and the US Environmental Protection Agency (EPA) Health Effects Test Guidelines OPPTS 870:1100, 1998.

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2268 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).

The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study.

All animals showed an expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute oral LD0 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg active ingredient/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Test type:
standard acute method
Species:
rat
Route of administration:
inhalation: vapour
Endpoint conclusion
Endpoint conclusion:
no study available

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to the OECD guideline 402 and GLP compliant
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Inc. on May 20, 2011.
- Age at study initiation: 9 weeks
- Weight at study initiation: 233-249 grams and females 172-184 grams
- Fasting period before study: no
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 45-78% The humidity was above the targeted upper limit for four days during the study. A portable dehumidifier was used to lower the humidity levels during this time. This slightly increased humidity does not affect the integrity of this study.
- Air changes (per hr): 12 to 14
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 2 inches x 3 inches
- % coverage: approximately 10% of the body surface
- Type of wrap if used: 3-inch Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently cleaning of any residual test substance.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg
- Constant volume or concentration used: yes

VEHICLE
none
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: during the first severa! hours after application and at !east once daily thereafter for 14 days.
- Frequency of weighing: prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality
Mortality:
All animals survived exposure to the test substance during the study.
Clinical signs:
Dermal irritation was noted at the dose site of all animals between Days 1 and 14.
Body weight:
Although two females lost weight through Day 7, all animals gained body weight over the 14-day observation period.
Gross pathology:
No gross abnorrnalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

 

INDIVIDUAL CAGE-SIDE OBSERVATIONS

Animal number

Findings

Day of occurence

Males

 

 

3201

Active and healthy

0(1-4.5 hrs), 8-14

 

Erythema at dose site

1-4

 

Desquamation at dose site

 5-7

3202

Active and healthy

 0(1-4.5 hrs), 4-14

 

Erythema at dose site

 1-3

3203

Active and healthy

0(1-4.5 hrs), 7-14

 

Erythema at dose site

 1-3

 

Desquamation at dose site

 3-5

 

Small areas of eschar at dose site

 5-6

3204

Active and healthy

 0(1-4.5 hrs)

 

Blanching

 1-4

 

Erythema at dose site

 1-5

 

Areas of dark discoloration at dose site

1-5

 

Small areas of eschar at dose site

 5-7

 

Eschar at dose site

 8-14

3205

Active and healthy

0(1-4.5 hrs), 14

 

Blanching

 1-4

 

Erythema at dose site

 1-5

 

Areas of dark discoloration at dose site

 1-5

 

Small areas of eschar at dose site

5-13

 

Animal number

Findings

Day of occurence

3206

Active and healthy

0 (1-4.5 hrs), 14

Females

 

 

 

Erythema at dose site

1-5

 

Areas of dark discoloration at dose site

1-6

 

Small areas of eschar at dose site

5-13

3207

Active and healthy

0(1-4.5 hrs)

 

Erythema at dose site

1-3

 

Desquamation at dose site

4-12

 

Small areas of eschar at dose site

5-14

3208

Active and healthy

 0(1-4.5 hrs), 12-14

 

Erythema at dose site

1-4

 

Areas of dark discoloration at dose site

1-6

 

Desquamation at dose site

5

 

Small areas of eschar at dose site

5-11

3209

Active and healthy

0(l-4.5hrs), 14

 

Areas of dark disco1oration at dose site

1-4

 

Erythema at dose site

1-1 1

 

Desquamation at dose site

 5-7

 

Small areas of eschar at dose site

5-13

3210

 Active and healthy

0(1-4.5 hrs)

 

Erythema at dose site

1-4

 

Blanching

1-4

 

Areas of dark discoloration at dose site

1-6

 

Small areas of eschar at dose site

5-6, 14

 

Eschar at dose site

7-13

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the single dose acute dermal LD0 of N-(3-Aminopropyl)diethanolamine is greater than 2,000 mg/kg of body weight in male and female rats.
Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for N-(3-Aminopropyl)diethanolamine

to produce toxicity from a single topical application.

Two thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily lor 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived exposure to the test substance during the study. Dermal irritation was noted at the dose site of all animals between Days 1 and 14. Although two females lost weight through Day 7, all animals gained body weight over the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD0 of N-(3-Aminopropyl)diethanolamine

is greater than 2,000 mg/kg of body weight in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Study complete and sufficient to fulfill the endpoint requirements.

Additional information

Acute oral toxicity

The study was performed to assess the acute oral toxicity of N-(3-Aminopropyl)diethanolamine in the Sprague-Dawley CD strain rat (Allen, 1998). The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987), Method 81 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC) and the US Environmental Protection Agency (EPA) Health Effects Test Guidelines OPPTS 870:1100, 1998. Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2268 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination. There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral LD0 of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg active ingredient/kg bodyweight.

 

Acute inhalation toxicity

No study is available.

 

Acute dermal toxicity

An acute dermal toxicity test was conducted with rats to determine the potential for N-(3-Aminopropyl)diethanolamine to produce toxicity from a single topical application (Lowe, 2011). Two thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily lor 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived exposure to the test substance during the study. Dermal irritation was noted at the dose site of all animals between Days 1 and 14. Although two females lost weight through Day 7, all animals gained body weight over the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Under the conditions of this study, the single dose acute dermal LD0 of N-(3-Aminopropyl)diethanolamine is greater than 2,000 mg/kg of body weight in male and female rats.


Justification for selection of acute toxicity – oral endpoint
Study performed according to the OECD guideline 401 and GLP compliant.

Justification for selection of acute toxicity – dermal endpoint
Study performed according to the OECD guideline 402 and GLP compliant

Justification for classification or non-classification

Acute oral toxicity: LD0>2000mg/kg. No classification required according to CLP and DSD criteria.

Acute inhalation toxicity: no data available.

Acute dermal toxicity: LD0>2000mg/kg. No classification required according to CLP and DSD criteria.