N,N-bis(2-hydroxyethyl)glycine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 December 2016 - 21 December 2016

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:

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:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(2-hydroxyethyl)glycine

EC Number:

205-755-1

EC Name:

N,N-bis(2-hydroxyethyl)glycine

Cas Number:

150-25-4

Molecular formula:

C6H13NO4

IUPAC Name:

N,N-bis(2-hydroxyethyl)glycine

impurity 1

Reference substance name:

N-(2-hydroxyethyl)ethylenediaminetriacetic acid

EC Number:

205-759-3

EC Name:

N-(2-hydroxyethyl)ethylenediaminetriacetic acid

Cas Number:

150-39-0

Molecular formula:

C10H18N2O7

IUPAC Name:

N-{2-[bis(carboxymethyl)amino]ethyl}-N-(2-hydroxyethyl)glycine

impurity 2

Reference substance name:

Not specified

IUPAC Name:

Not specified

impurity 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Dihydrogen oxide

Test material form:

solid: crystalline

Details on test material:

Appearance: white crystalline powder
Storage conditions: at room temperature protected from light

Specific details on test material used for the study:

Solubility in water: 167.13 g/L (20°C)
pH: 4-5 (10% solution)

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 – 20.8
- Humidity (%): 39 - 48
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of daily mean relative humidity occurred. However, laboratory historical data do not indicate an effect of the deviations and therefore it is not considered to affect the study adversely.

IN-LIFE DATES: From: 6 December 2016 to 21 December 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes, the test item preparations were stirred on a magnetic stirrer during dosing.

Frequency: single dosage, on Day 1.

VEHICLE:
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at Charles River Den Bosch and on test item data supplied by the Sponsor. There was no information available regarding the stability in vehicle.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The preparations (w/w) were kept at room temperature protected from light and were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. No correction was made for purity of the test item.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: Yes, descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture, piloerection and/or quick breathing were noted for all animals on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

(Also, not classified according to CLP)

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw for Bicin was determined. Based on these results, The substance does not meet GHS and CLP criteria for classification.