Registration Dossier

Administrative data

Description of key information

An acute oral toxicity study is available; waivers are provided for acute dermal toxicity and acute inhalation toxicity, based on the corrosivity of the substance.

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:
guideline study with acceptable restrictions
Remarks:
incomplete characterization of the test substance (no data on test substance purity available)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Report title states test material is N, N, N Trimethylaminoethyl-Ethanolamin.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Further characterisation: KFM-Han. Wistar (outbred, SPF-Quality)
Source: Kleintierfarm Madoerin AG , CH 4414 Fuellinsdorf / Switzerland
Age at study initiation: 9 - 11 wks
Weight at study initiation: 201 - 227 g (males), 173 - 204 g (females)
Fasting period before study: 12 to 18 hours (access to water was not interrupted). Food was again presented approximately one hour after dosing.
Housing: Groups of five in Makrolon type-3 cages
Diet: Pelleted standard Kliba 343, Batch 47/86 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland); available ad libitum
Water: Community tap water from Itingen; available ad libitum
Acclimation period: at least 7 day
Other: analysis of feed and water for contamination and nutrients indicated no variations that would affect the outcome of the study

ENVIRONMENTAL CONDITIONS
Temperature (°C): 22 ± 3 °C
Humidity (%): 40 - 70 %
Air changes (per hr): 10 - 15
Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION
The test article was placed into a glass beaker on a tared Mettler PK 4800 balance, and the vehicle (distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, Staufen, FRG). Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Auer-Bittmann, 8953 Dietikon, Switzerland). The preparation was made immediately prior to dosing.

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
2,000, 3,200, 5,000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
Frequency of observations/mortality: Four times during test day 1, and daily during days 2-15
Frequency of weighing: Test days 1 (pre-administration), 8 and 15
Necropsy of survivors and animals that perished performed: yes
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex the slope of the dose response line were estimated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 801 mg/kg bw
Based on:
test mat.
Remarks:
(in water)
95% CL:
2 235 - 3 346
Remarks on result:
other: Slope = 5.373
Sex:
male
Dose descriptor:
LD50
Effect level:
3 081 mg/kg bw
Based on:
test mat.
Remarks:
(in water)
95% CL:
2 207 - 4 066
Remarks on result:
other: Slope = 5.242
Sex:
female
Dose descriptor:
LD50
Effect level:
2 570 mg/kg bw
Based on:
test mat.
Remarks:
(in water)
95% CL:
1 107 - 3 534
Remarks on result:
other: Slope = 3.913
Mortality:
Mortality: (out of 5 males and 5 females)
Number of dead males at doses 2,000, 3,200, 5,000 mg/kg bw: 0/3/5
Number of dead females at doses 2,000, 3,200, 5,000 mg/kg bw: 1/4/5
Clinical signs:
At 2,000 mg/kg bw: sedation, curved body position, ruffled fur
At 3,200 mg/kg bw: sedation, ataxia, ventral body position (males), latero-abdominal position (females), curved body position, ruffled fur
At 5,000 mg/kg bw: sedation, somnolence, ataxia, curved body position, tremor, ruffled fur.
The surviving rats recovered within 4 to 8 observation days.
Body weight:
No significant difference among the surviving animals (see table 2)
Gross pathology:
Animals that died:
At 2,000 mg/kg bw: red discolouration of lungs, stomach/intestines was filled with test article
At 3,200 mg/kg bw: dark-red discolouration of the lungs, stomach/intestines were totally filled with test article and/or reddish fluid, dark reddish discolouration of the stomach and intestines, severe enlargement of the stomach
At 5,000 mg/kg bw: dark-red discolouration of the lungs (not collapsed), stomach/intestines were partly or totally filled with reddish fluid and test article, dark reddish discolouration of the stomach, enlargement of the stomach and intestines

Animals that were sacrificed:
No pathological changes seen at any dose level

Mortality (out of 5/sex/dose)

 

 

 

 

 

 

 

 

Dose (mg/kg bw)

Gender

2 h

3 h

5 h

7 h

24 h

Total after 15 days

2,000

male

0

0

0

0

0

0

female

0

0

0

0

1

1

3,200

male

0

1

0

0

2

3

female

0

0

1

2

1

4

5,000

male

0

0

1

2

2

5

female

0

1

3

0

1

5

 

Mean weight (g)

Dose (mg/kg bw)

Gender

Day 1

Day 8

Day 15

2000

male

214 ± 8.1

248 ± 11

279 ± 14

female

193 ± 5.4

204

222

3200

male

205 ± 7.7

229

265

female

180 ± 3.7

201

228

5000

male

213 ± 6.9

All dead

-

female

185 ± 13

All dead

-

 

Clinical signs

Dose (mg/kg bw)

2000

3200

5000

 

 male

 female

 male

 female

 male

female

Sedation

≤ 24 hours

≤ 24 hours

≤ 6 days

≤ 6 days

2 – 5 h

2 – 5 h

Curved body position

≤ 24 hours

≤ 24 hours

≤ 5 days

≤ 5 days

2 – 5 h

2 – 5 h

Ruffled fur

≤ 48 hours

≤ 48 hours

≤ 6 days

≤ 6 days

2 – 5 h

2 – 5 h

Ataxia

-

-

≤ 5 days

≤ 5 days

2 – 5 h

2 – 5 h

Central body position

-

-

2 h

-

-

-

Latero-abd-pos

-

-

-

2 – 5 h

-

-

Tremor

-

-

-

-

2 – 5 h

2 – 5 h

Somnolence

-

-

-

-

2 – 5 h

2 – 5 h

h: hour

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 values were 3081 mg/kg bw (males), 2570 mg/kg bw (females) and 2801 mg/kg bw (combined males and females). The substance is not classified for acute toxicity accoridng to the CLP Regulation.
Executive summary:

An acute oral toxicity was conducted in rats according to OECD 401 and EU methods B.1. N, N, N Trimethylaminoethyl-Ethanolamin was adminstered by oral gavage to 5 rats/sex/group at dose levels of 2000, 3200 and 5000 mg/kg bw. Mortality was observed at all doses; all animals dosed with 5000 mg/kg bw died, seven animals dosed with 3200 mg/kg bw died and one animal dosed with 2000 mg/kg bw died. Clinical signs included sedation, curved body position, ruffled fur, somnolence, ataxia and tremors. In those animals which died during the study, red discoloration of the lungs, stomach and intestines filled with test article and/or red fluid, red discolouration of the stomach and intestines and enlargemet of the stomach and intestines were observed. No pathological changes were noted in animals surviving to the scheduled termination. The LD50 values were 3081 mg/kg bw (males), 2570 mg/kg bw (females) and 2801 mg/kg bw (combined males and females). In accordance with CLP, classification for acute oral toxicity is not required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 570 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 study available

Additional information

An acute oral toxicity was conducted in rats according to OECD 401 and EU methods B.1. N, N, N Trimethylaminoethyl-Ethanolamin was adminstered by oral gavage to 5 rats/sex/group at dose levels of 2000, 3200 and 5000 mg/kg bw. Mortality was observed at all doses; all animals dosed with 5000 mg/kg bw died, seven animals dosed with 3200 mg/kg bw died and one animal dosed with 2000 mg/kg bw died. Clinical signs included sedation, curved body position, ruffled fur, somnolence, ataxia and tremors. In those animals which died during the study, red discoloration of the lungs, stomach and intestines filled with test article and/or red fluid, red discolouration of the stomach and intestines and enlargemet of the stomach and intestines were observed. No pathological changes were noted in animals surviving to the scheduled termination. The LD50 values were 3081 mg/kg bw (males), 2570 mg/kg bw (females) and 2801 mg/kg bw (combined males and females). In accordance with CLP, classification for acute oral toxicity is not required.

Waivers are provided for acute dermal toxicity and acute inhalation toxicity, based on the corrosivity of the substance.

Justification for classification or non-classification

No classification for acute oral toxicity is required, based on the available study. LD50 values are reported to be >2000 mg/kg bw; therefore classification under CLP is not required.