2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-10-04 to 2016-10-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17th December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30th May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

EC Number:

230-237-7

EC Name:

2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

Cas Number:

6976-37-0

Molecular formula:

C8H19NO5

IUPAC Name:

2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 199 - 201 g
- Fasting period before study: food for 1 day before treatment and 3 h after treatment, water was available
- Housing: group caging (3 rats/cage), cage Type II polypropylene/polycarbonate
- Diet: ad libitum, ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany
- Water: ad libitum, tap water
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): above 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: standard vehicle
- Purity: aqua purificata Ph.Hg. VIII. from Parma Produkt Kft.

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Selection was based on the basis of the available information about the test item and similar substances

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter. The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, external appearance and appearance of tissue and organs of cranial, thoracic and abdominal cavities

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw: 0 of 6

Clinical signs:

other: No symptoms were observed throughout the 14-day post-treatment period at any groups of the female animals.

Gross pathology:

No pathological changes were found during the macroscopic examination of animals.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP-study according to OECD TG 423 (acute class method) with rats, the LD50 of the substance was determined as > 2000 mg/kg bw.

Executive summary:

A study according to OECD 423 was conducted to determine the acute oral toxicity of the test item in rats. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out after termination of the observation period. All female rats survived until the end of the 14-day observation period. No symptoms were observed throughout the 14-day post-treatment period at any animals. The body weight development was undisturbed in all animals. All organs of the animals treated with 2000 mg/kg bw proved to be free of gross pathological changes. As no animal died in the first and second treatment group at 2000 mg/kg bw the stopping criteria of Annex 2d of OECD Guideline No. 423 was met and no further treatment group was initiated. In conclusion, the LD50 of the test item was considered to be above 2000 mg/kg body weight by oral route in the rat.