Fatty acids, C16-18 (even numbered), reaction products with diethylene triamine, di-Me sulfate quaternized

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-07-26 to 2017-10-12

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:

17 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:

30 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:

Imidazolium compounds, 2-(C15 and C17 -alkyl)-1-[2-(C16 and C18) amidoethyl]-4,5-dihydro-(1 or 3)-methyl, Me sulfates

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Imidazolium compounds, 2-(C15 and C17 -alkyl)-1-[2-(C16 and C18) amidoethyl]-4,5-dihydro-(1 or 3)-methyl, Me sulfates

Constituent 2

Reference substance name:

Imidazolium compounds, 2-(C15 and C17)-1-[2-(C16 and C18) amidoethyl]-4,5-dihydro, Me sulfates

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Imidazolium compounds, 2-(C15 and C17)-1-[2-(C16 and C18) amidoethyl]-4,5-dihydro, Me sulfates

Constituent 3

Reference substance name:

N,N,N-trimethyl-2-[2-(C15 and C17)]-4,5-dihydro-1H-imidazol-1-yl)ethanaminium, Me sulfates

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

N,N,N-trimethyl-2-[2-(C15 and C17)]-4,5-dihydro-1H-imidazol-1-yl)ethanaminium, Me sulfates

1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

2

Reference substance name:

Glycerides, C16-18 mono-

EC Number:

293-208-8

EC Name:

Glycerides, C16-18 mono-

Cas Number:

91052-47-0

Molecular formula:

C19H38O4 to C21H42O4

IUPAC Name:

Glycerides, C16-18 mono-

Test material form:

not specified

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 185-197 g
- Fasting period before study: 16 h before administration
- Housing: individually or pair in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (e.g. ad libitum): ad libitum until 16 h before the first administration, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 12 to 18
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): The test item was suspended in sesame oil to a concentration of 500 mg/mL, considering the correction factor of 1.32.

CLASS METHOD (if applicable) Acute toxic class
- Rationale for the selection of the starting dose: 5000 mg/kg bw as recommended by the guideline.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days. During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working
day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD 50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: Under the present test conditions, a single oral administration of 5000 mg test item/kg b.w. revealed slightly reduced motility, ataxia, reduced muscle tone and dyspnoea 15 minutes after administration until test days 3 or 4 and, in

Gross pathology:

No pathological changes were observed at necropsy.

Any other information on results incl. tables

Tabel 1: Summarized results

5000 mg test irem/kg b.w., p.o.

Symptoms/Criteria	(n = 1) femalefirst step	(n = 2) femalessecond step
Clinical signs
reduced motility	+15'-TD 4 (1)
ataxia	+15'-TD 4(1)
reduced muscle tone	+15'-TD 3(1)
dyspnoea	+15'-TD 3(1)
forepaw bloody	+3h-TD 3(1)
forepaw with scab	+TD 4-TD 7(1)
Mortality
within 6h	0
within 24 h	0
within 7 days	0
within 14 days	0
Mean body weight (in g)
start	185	193.5
after 7 days	192 (+3.8)	220.5 (+14.0)
after 14 days	223 (+ 20.5	229.5 (+18.6)
inhibition of body weight gain	none	none
necropsy findings	none	none

in brackets:   number of animals affected

':                                                       minutes
h:                                                      hours

TD:                                                    test day
b.w.:                                                  body weight
p.o.:                                                   per oral

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the present study 3 female Sprague Dawley rats were administered 5000 mg/kg bw of the test item by gavage and observed for 14 days. Clinical signs were only detected in one of the animals and were reversible. No premature death occurred and there were no findings at necropsy of the animals, thus, the substance does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Executive summary:

In an acute oral toxicity study according to OECD guideline 404, three female Sprague Dawley rats, weighing 185- 197g and aged approximately 8 weeks old were given a single oral dose of IS-2017-761 (100 % a.i.) in sesame oilat a dose of 5000 mg/kg bw and observed for 14 days.

 

Oral LD₅₀Females ≥  5000 mg/kg bw

Limit test, no mortality was observed

IS-2017-761 is of LOW Toxicity based on the LD₅₀in female Sprague Dawley rats. There were no treatment related clinical signs, necropsy findings or changes in body weight, thus the substance does not need to be classififed according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).