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Description of key information

The LD50 value derived from the oral acute toxicity study with AEEA is 2150 mg/kg bw. The dermal LD50 was >2000 mg/kg bw. In two inhalation studies a LC0 value of 51.3 mg/m³ (saturated atmosphere) was established. The acute toxicity studies for the dermal and inhalative administration showed no mortality, only some weak clinical symptoms were noted.

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: Comparable to GLP guideline study with acceptable restrictions. Low purity of test substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: DR. K . THOMAE GMBH, D-7950 BIBERACH . FRG
- Age at study initiation: young adult
- Weight at study initiation: male: 181-191 g , female 169-179 g
- Fasting period before study: 16 h
- Housing: stainless steel wire mesh cages type DK-III (Becker & Co. Castrop-Rauxel. FRG)
- Diet: KLIBA-Labordiet FA. Klingentalmühle AG CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h



Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 , 31.6 , 21.5 , 14.7 w/v

DOSE VOLUME APPLIED:
- 10 mL / kg (for all dose levels)

Doses:
1470; 2150; 3160; 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs were assessed at least once each work day and body weights were recorded on days 3, 5, 7 and 13
- other: check for moribund and dead animals was performed twice on workdays and once on holidays
- Necropsy of survivors performed: yes
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 150 mg/kg bw
Remarks on result:
other: calculated combined for males and females
Mortality:
please refer to "Remarks on results tables and figures"
Clinical signs:
Animals of both sexes receiving 3160 or 5000 mg/kg bw showed symptoms from 30 min until 4 hrs. after dosing. The symptoms included dyspnoea,apathy, staggering, and poor general state. Animals at 2150 mg/kg bw showed the same symptoms, but the onset (after 4 hrs) and duration (1 day) were delayed.
Spastic gait was seen at the highest dose only. Piloerection
was noted at the two intermediate dose levels only.
Body weight:
No effect on mean body weight was noted during the study period.
Gross pathology:
Necropsy revealed no abnormalities in animals that survived. In animals that died a general congestive hyperemia was noted. Stomach was found dilated with red liquid contents, hemorrhagic gastritis in animals at 5000 mg/kg bw. The intestines also contained red liquids, the mucosa of the
small intestine was often found deep-red. This is probably due to the caustic nature of AEEA.

Mortality was noted as follows:

 

 

 

 

Sex

Dose Group [mg/kg bw]

 

1470

2150

3160

5000

 

 

 

 

 

Males

0/5

3/5

5/5

5/5

Females

0/5

1/5

5/5

5/5


Executive summary:

In this acute oral toxicity study (BASF AG, Department of Toxicology, 1986), groups of fasted, young adult wistar rats (5/sex) were given a single oral dose of AEEA (70 -85 % a.i.) in destilled water at doses of  1470, 2150, 3160 or  5000  mg/kg bw and observed for 14 days.

 

Oral LD50

Males =  2150 mg/kg bw

Females = 2380 mg/kg bw

Combined =  2150 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 150 mg/kg bw
Quality of whole database:
Comparable to Guideline study.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed prior to the implementation of GLP and OECD Guidelines, but is in compliance with the principles described in OECD Guideline 403. Observation period is not reported.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Several groups of usually 3 rats per sex were exposed sequentially to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for different time periods ( 8 hours). The exposure time not causing lethality was usually testedtwice.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
saturated atmosphere at 20 °C.
No. of animals per sex per dose:
3 rats (total of 12 rats)
Control animals:
no
Details on study design:
- The animals were observed for signs of toxicity and mortality.
- Necropsy of survivors performed: yes
Sex:
not specified
Dose descriptor:
LC0
Effect level:
51.3 mg/m³ air
Exp. duration:
8 h
Remarks on result:
other: saturated atmosphere
Mortality:
No mortality (0/12) was seen.
Gross pathology:
Apart from strong eye irritation no findings were noted at necropsy.
Other findings:
- Other observations: Animals tried to escape upon start of exposure. 
Effect level:

Animals were exposed to AEEA in a saturated atmosphere at 20 °C. No exposure concentration was reported. As the vapour pressure of AEEA is 0.012 hPa at 20 °C (calculated), a saturated atmosphere corresponds to 51.3 mg/m³.

Executive summary:

In this acute inhalation toxicity study a total of 12 rats (two times 3/sex) were whole body exposed to AEEA (saturated atmosphere at 20 °C) for 8 hours. Animals then were observed. Animals tried to escape upon start of exposure. No mortality occured. Apart from strong eye irritation no findings were noted at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
51.3 mg/m³
Quality of whole database:
Study was performed prior to the implementation of GLP and OECD Guidelines, but is in compliance with the principles described in OECD Guideline 403.

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)
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute 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: SPF-Breed, Wiga, Sulzfeld, Germany
- Age at study initiation: young adult
- Weight at study initiation: male: 145 g , female 127 g
- Diet: concentrated feed, Eggersmann, Rinteln/Weser, Germany, ad libitum
- Water : tap water ad libitum
Type of coverage:
occlusive
Vehicle:
other: applied in olive oil and as neat substance
Details on dermal exposure:
TEST SITE
- Area of exposure: 11.5 cm² of the intact dorsal skin clipped 24 h before treatment
- coverage: 100 %
- Type of wrap if used: inert foil


REMOVAL OF TEST SUBSTANCE
- Washing: after 24 h with warm water


Duration of exposure:
24 h
Doses:
400 mg/kg bw (olive oil), 2000 mg/kg bw (neat)
No. of animals per sex per dose:
10/10 and 5/5 (males/females) for the 400 and 2000 mg/kg bw dose levels, respectively
Control animals:
no
Details on study design:
- Duration of observation period following administration: the animlas were observed for signs of toxicity during the 14-day observation ( after observation period animals were sacrified and necropsied)
- Necropsy of survivors performed: yes
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
- no mortality was seen at either dose level
Clinical signs:
- no signs of systemic toxicity were seen at either dose level
Gross pathology:
- during terminal necropsy pale kidneys were occasionally noted
- local skin irritation was noted 24 hours after application which led to scar formation within 14 days
Executive summary:

In this acute dermal toxicity study groups of young adult Sprague Dawley rats were dermally exposed to AEEA (> 98 % a.i) at doses of 400 (in olive oil, 10/sex) and 2000 mg/kg bw (neat substance, 5/sex) for 24 hours to an area of 11.5 cm². Animals then were observed for 14 days. During terminal necropsy pale kidneys were occasionally noted and local skin irritation was noted 24 hours after application which led to scar formation within 14 days. No mortality and no signs of systemic toxicity were seen at either dose level.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Guideline study

Additional information

Oral route:

In a acute oral toxicity study (BASF AG, Department of Toxicology, 1986), groups of fasted, young adult wistar rats (5/sex) were given a single oral dose of AEEA (70 -85 % a.i.) in destilled water at doses of 1470, 2150, 3160 or 5000  mg/kg bw and observed for 14 days.

 

Oral LD50

Males =  2150 mg/kg bw

Females = 2380 mg/kg bw

Combined = 2150 mg/kg bw

 

Inhalation route:

In an acute inhalation toxicity study (BASF AG, Department of Toxicology, 1970) a total of 12 rats (two times 3/sex) were whole body exposed to AEEA (saturated atmosphere at 20 °C) for 8 hours. Animals then were observed. Animals tried to escape upon start of exposure. No Mortality occured. Apart from strong eye irritation no  findings were noted at necropsy.

 

In another acute inhalation toxicity study (Myers RC & Ballantyne B, 1997), groups of 6 young adult female Wistar rats were exposed by inhalation route to AEEA for 6 -8 hours (saturated atmosphere, whole body). Animals then were observed for 14 days. During the observationperiod weight gain was normal, and no mortality occured. Necropsy showed no gross findings. In both studies a LC0 value of 51.3 mg/m³ (saturated atmosphere) was established.

 

Dermal route:

In an acute dermal toxicity study (BASF AG, Department of Toxicology, 1980) groups of young adult Sprague Dawley rats were dermally exposed to AEEA (>98 % a.i) at doses of 400 (in olive oil, 10/sex) and 2000 mg/kg bw (neat substance, 5/sex) for 24 hours to an area of 11.5 cm². Animals then were observed for 14 days. During terminal necropsy pale kidneys were occasionally noted and local skin irritation was noted 24 hours after application which led to scar formation within 14 days. No mortality and no signs of systemic toxicity were seen at either dose level.


Justification for selection of acute toxicity – oral endpoint
The Key study (BASF AG, 1986) was selected.

Justification for selection of acute toxicity – inhalation endpoint
The Key study (BASF AG, 1970) was selected.

Justification for selection of acute toxicity – dermal endpoint
The Key study (BASF AG, 1980) was selected.

Justification for classification or non-classification

Based on the results of the acute oral, dermal and inhalation key toxicity studies, AEEA is not subjected to classification and labelling for acute toxic effects according to Directive 67/548/EEC and Regulation 1272/2008/EC.