Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 05 October 2017 to 07 November 2017

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:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

On one occasion the temperature and humidity values were not recorded

Principles of method if other than guideline:

On one occasion the temperature and humidity values were not recorded. The maximum and minimum values taken the next day were within the required limits therefore they were within limits on the day the recording was not taken. This deviation from protocol therefore had no impact on the integrity or the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

morpholin-4-ium morpholine 6-(4-methylbenzenesulfonamido)hexanoate

EC Number:

944-090-8

Molecular formula:

C13H19NO4S.C4H9NO/C4H9NO/H2O

IUPAC Name:

morpholin-4-ium morpholine 6-(4-methylbenzenesulfonamido)hexanoate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 to 10 weeks old
- Weight at study initiation: 157 to 183 g
- Fasting period before study: from the evening of the day prior to dosing until approximately 3 hours after dosing
- Housing: 5 animals per cage conforming to the 'Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes’ (Home Office, London, 2014).
- Diet: 5LF2 EU Rodent Diet 14% ad libitum
- Water: ad libitum
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): 15 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL or 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The test item is soluble in water.

- Rationale for the selection of the starting dose: LD50 was assumed to be comprised between 300 and 2,000 mg/kg bw as a worst-case scenario taking into account the acute oral toxicity of one of the constituents of the substance.

Doses:

A preliminary study was performed at 300 mg/kg bw and 2,000 mg/kg bw. Main study was performed at 2,000 mg/kg bw.

No. of animals per sex per dose:

One animal per dose for the preliminary study.
Four animals per dose for the main study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat. Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

No animal died during the preliminary study at 300 mg/kg bw or 2,000 mg/kg bw.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died as a result of the treatment.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

See attached background material

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in rats was concluded to be above 2,000 mg/kg body weight. Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) does not meet the criteria for classification in accordance with Regulation (EC) No.1272/2008.

Executive summary:

The acute oral toxicity of the test item Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) was evaluated during a GLP-compliant study performed in accordance with the OECD Testing Guideline 420.

During a preliminary study, one female Wistar rats received a single dose of 300 mg/kg bw of 2,000 mg/kg bw of the test substance. Considering that no death was observed, four female Wistar rats received a single dose of 2,000 mg/kg of the test substance during the main study.

Animals were observed for 14 days following the administration of the test substance. Mortality, clinical signs, and bodyweight were recorded. At the end of the observation period, animals were sacrificed and a necropsy was performed.

No animal died as a result of the treatment with Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1). No clinical signs were observed and the animals showed the expected bodyweight increase. There was no treatment-related finding during the necropsy.

It can be concluded that the substance has a LD₀ of 2,000 mg/kg bw and a LD₅₀ above 2,000 mg/kg bw. Therefore reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) does not meet the criteria for classification in accordance with Regulation (EC) No.1272/2008.