Tris(2-hydroxyethyl)ammonium acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1999-07-21 to 1999-08-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is the result of a structural analogue substance used as read-across substance. Study is conducted according to Guidelines in a GLP certified laboratory.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

444-360-0

EC Name:

-

IUPAC Name:

444-360-0

Details on test material:

- Physical state: Pale Yellow Liquid
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature (17 - 23 degrees C) away from direct sunlight.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd.,
Biotechnology & Animal Breeding Division,
CH-4414 Fullinsdorf,
Switzerland.
- Age at study initiation: Males: 8 weeks
Females: 10 weeks
- Fasting period before study: Overnight fasting prior to intubation
- Housing: Groups of three in MAkrolon type -4 cages with standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, batch no. 37/99, rat maintenance diet.
- Water (e.g. ad libitum): Community tap water from Itingen
- Acclimatisation: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light.


IN-LIFE DATES: From: July 21 -27, 1999 (Females) July 23 - 29, 1999 (males) To: August 11, 1999 (Females) August 13, 1999 (Males)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Bi-distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2g/ml
- Amount of vehicle (if gavage): 10 ml/kg


DOSAGE PREPARATION (if unusual): The test article was placed into a glass beaker on a tared Mettler balance and the vehicle was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogenicity of the test article was in the vehicle was maintained during treatment.

The preparation was made shortly before each dosing.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 animals per sex. Only one dose (2000 mg/kg) was used.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality / viability: four times during test day 1 and once daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: Changes in appearance and behaviour were examined four times during day 1 nad once daily during days 2-15
body weight: Animals were weighed on test day 1 (pre-administration), day 8 and day 15.

Statistics:

No statistical analysis was performed as no deaths occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No death occurred during the study.

Clinical signs:

other: No clinical signs were noted during the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Table 1: Individual Findings - Clinical Signs

Sex	Animal No.	Signs	Test Day
			1				2	3	4	5	6	7	8	9	10	11	12	13	14	15
			1h	2h	3h	4h
Female 2000 mg/kg	1	No clinical signs
	2	No clinical signs
	3	No clinical signs
Male 2000 mg/kg	1	No clinical signs
	2	No clinical signs
	3	No clinical signs

Table 2: Body Weights

Body Weight in grams
Sex	Animal No.	Day of Treatment	Day 8	Day 15
Female 2000 mg/kg	1 2 3	175.9 181.4 180.0	204.2 202.9 208.1	217.7 214.9 218.9
Male 2000 mg/kg	1 2 3	206.7 211.7 211.1	264.8 260.1 258.3	289.6 286.4 275.8

Table 3: Macroscopic Findings

Sex	Animal No.	Type of death	Findings
Female 2000 mg/kg	1	Scheduled necropsy	No macroscopic findings
	2	Scheduled necropsy	No macroscopic findings
	3	Scheduled necropsy	No macroscopic findings
Male 2000 mg/kg	1	Scheduled necropsy	No macroscopic findings
	2	Scheduled necropsy	No macroscopic findings
	3	Scheduled necropsy	No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The LD50 of Read Across substance 1 (RA1) after single oral administration to rats of both sexes, observed over a period of 14 days was greater than 2000 mg/kg body weight.

Executive summary:

The Read Across test substance RA1 was evaluated for its potential to produce death following oral administration at a dose of 2000 mg/kg in male and female Wistar rats.

Animals were administered a single dose of the test substance on a mg/kg bw basis by oral gavage following fasting for approximately 16.5 hours, but with free access to water. Three hours after dosing, the animals were returned to their cages and supplied with feed and water ad libitum.

No mortalities or clinical signs were observed during the study and the body weight of the animals was within the range commonly recorded for this strain and age.

Based on these results, the medial lethal dose (LD50) of RA after single oral administration to rats of both sexes, observed over a period of 14 days was greater than 2000 mg/kg body weight.