Reaction mass of L-Glutamic acid, N-coco acyl derivs., monosodium salts and sodium hydrogen N-(1-oxooctadecyl)-L-glutamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 January 2009 and 12 February 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with GLP and agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Remarks:

Study conducted on read-across material

Justification for type of information:

A RAAF report will shortly be provided.

Cross-reference

Reason / purpose for cross-reference:

other: Read-across target

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

A RAAF report will shortly be provided.

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Signature: 15/10/2007 Date of Inspection: 21/08/2007

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

EC Number:

936-610-7

Molecular formula:

See remarks

IUPAC Name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

Constituent 2

Reference substance name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

IUPAC Name:

Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing:The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum):Free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water.
- Acclimation period: Acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature were set to achieve limits of 19 to 25°C.
- Humidity (%): Relative humidity were set to achieve limits 30 to 70%.
- Air changes (per hr): rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From:Day 0 To:Day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200mg/ml
- Amount of vehicle (if gavage):10ml/kg
- Justification for choice of vehicle:. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): Not available
- Purity: Not available


MAXIMUM DOSE VOLUME APPLIED: 10ml/kg


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg bodyweight.

Doses:

A total of five animals were treated at a dose level of 2000 mg/kg in the study.

No. of animals per sex per dose:

Starting dose -1 female rat dose level-2000mg/kg
Additional group - 4 female rats dose level-2000mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Clinical observations were made ½, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

None

Results and discussion

Preliminary study:

There were no deaths.
No signs of systemic toxicity were noted.
No abnormalities were noted at necropsy.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

Individual necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Table1              Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Table2              Individual Bodyweights and Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	208	219	223	11	4
	2-0 Female	171	184	193	13	9
	2-1 Female	183	187	194	4	7
	2-2 Female	186	199	209	13	10
	2-3 Female	184	197	211	13	14

 

Table3              Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Female	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Killed Day 14	No abnormalities detected

0= No signs of systemic toxicity

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted)

§        Method B1bisAcute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as asuspensioninarachis oil BP, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).