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Description of key information

Oral (OECD 423), rat: LD50 = 5000 mg/kg bw (cut-off value, limit test)
Dermal, rat: LD50 > 2000 mg/kg bw

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
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: SPF, Crj:CD(SD)IGS
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Co., Japan
- Age at study initiation: 8 weeks
- Weight at study initiation: 179 - 211 g (mean: 190 g)
- Housing: The animals were housed one per cage in mesh cages
- Fasting: From approximately 16 hours prior to dosing until 4 hours after dosing
- Diet: CRF-1 pellets (Oriental Yeast Co.), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 hours
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The concentration was adjusted to administer the animals 10 mL/ kg bw
- Amount of vehicle (if gavage): 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to OECD 423, the initial dose shoud be 300 mg/kg bw. If no mortalities occur during 2 separate administrations of 300 mg/kg bw (step 1 and 2), the dose should be increased to 2000 mg/kg bw. The 2000 mg/kg bw dose was also administered in two separate groups (step 3 and 4).
Doses:
Step 1: 300 mg/kg bw
Step 2: 300 mg/kg bw
Step 3: 2000 mg/kg bw
Step 4: 2000 mg/kg bw
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs 5, 15 and 30 minutes; and 1, 2, 4 and 6 hours after dosing, and every day during the observation period thereafter. Body weights were measured before dosing on day 0 and on day 1, 2, 3, 7, 10 and 14.
- Necropsy of survivors performed: Yes. At the end of 14 days, the surviving animals were weighed, sacrificed and examined for gross pathological changes.
Statistics:
An average of the lethal dose was estimated from the numbers of dead animals per each dose. The mean body weight and standard deviation was calculated for each administration day.
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No effects were observed up to and including the highest dose level. According to OECD 423, the LD50 cut-off is set at 5000 mg/kg bw.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed during the observation period.
Body weight:
No changes in body weight between the control and treatment groups were observed.
Gross pathology:
No abnormalities were observed in any of the animals in the control or treatment groups.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity: oral

In the study performed by Nishimura (2004) according to OECD 423 (limit test), 3 females per group were administered 300 mg/kg bw 2-amino-2-ethyl-1,3-propanediol (AEPD) by gavage, in two consecutive steps. As no mortality was observed at the 300 mg/kg bw dose level, 2 groups of 3 animals were administered 2000 mg/kg bw, in two consecutive steps. Again, there was no mortality. No clinical signs and no effects on body weight were observed during the 14-day observation period in any of the animals. According to the acute toxic class method described in the OECD guideline 423, if there is no mortality following administration of 2000 mg/kg bw in two separate steps, the LD50 cut-off limit is 5000 mg/kg bw. Therefore, the LD50 is considered to be 5000 mg/kg bw for female rats. In a study performed according to the 1979 version of 16 CFR 1500.3 (Parekh, 1982), male and female rats were administered 1800, 2500, 3500 and 5000 mg/kg bw of the test substance per oral. The mortality was 0, 1, 5 and 5 for the males and 0, 1, 2, and 9 for the females, respectively, listed by increasing dose. In the rats that died, severe stomach- and intestinal haemorrhage was noted, indicating a local irritating effect of the test substance due to the alkaline pH value. The calculated LD50 for females was 3882 mg/kg bw and for males the LD50 was 4571 mg/kg bw. A relatively old study (Rubenkoenig, 1955) was also available, in which mice were administered 1000, 1500, 2000, 3000, 3600 and 4250 mg/kg bw AEPD, using 10 animals per dose level. The mortality was 0, 1, 3, 7, 10 and 10, respectively, by increasing dose. The estimated LD50 (oral) was 2470 mg/kg bw for the sexes combined.

Acute toxicity: dermal

A non-standard acute dermal toxicity study was performed in rabbits (Parekh, 1982). The animals' abdomens were shaved free of hair, and the test area was abraded. 2000 mg/kg bw AEPD was spread over the prepared abdominal skin area, which was then covered with an occlusive dressing. After 24 hours, the skin area was cleaned and the animals were observed for 14 days following administration. No mortality was observed. There were no signs of toxicity, no effects on body weight and no unusual gross histopathological findings were noted. The exposed skin areas were necrotic and oedemateous within 24 hours of the administration. The LD50 is considered to be > 2000 mg/kg bw.

Acute toxicity: other routes

The acute effects of an intraperitoneal dose of AEPD on mice was assessed in a study performed by Rubenkoenig (1955). In the groups administered 250, 500, 750, 1000, 1250 and 1750 mg/kg bw (10 per dose), the mortality was 0, 1, 4, 8, 9 and 10, respectively. The calculated intraperitoneal LD50 was 790 mg/kg bw.

The test substance-related findings were comparable for oral and dermal routes of application in the acute toxicity studies; with the high LD50-values indicating that AEPD has a very low potential to cause acute toxicity via these routes.

Justification for classification or non-classification

The available data on acute toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

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