Sodium hydrogen N-(1-oxotetradecyl)-L-glutamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From January 15 2013 to 30 January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: See remarks

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficienses, which do not affect the quality of the relevant results. The sudy report was conclusive, done to a valid guideline and the study was conducted under GLP conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium (2S)-4-carboxy-2-(tetradecanoylamino)butanoate

Cas Number:

72716-26-8

Molecular formula:

C19H34NO5K

IUPAC Name:

Potassium (2S)-4-carboxy-2-(tetradecanoylamino)butanoate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Batch 110825
white powder
Shelf life 3 years from production date
Storage conditions room temperature (15 °C - 25 °C)
Routine safety protections

Test animals

Species:

rat

Strain:

Wistar

Remarks:

CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals:
- Weight at study initiation: 202 - 211 g
- Age at study initiation: young healthy adult rats, 9-10 weekd old
- Fasting period before study: overnight
- Housing: in groups of 3 per cage, standard housing conditions, Type II polypropylene/polycarbonate cages used
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 12 days
- Females are nulliparous and non pregnanat
Environmental conditions
- Temperature (°C): 19.2 - 21.9
- Humidity (%): 34 - 66
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 hours daily from 6.00 a.m. to 6.00 p.m

IN-LIFE dates: from 15 January 2013 to 30 January 2013

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Distilled water

Details on oral exposure:

Maximum volume applied: 10 ml/kg bw
The test material was freshly formulated at the concentation of 200 mg/ml in the vehicle. on the day of administration. The formulation container was stirred continuosly up to finishing the treatment.
CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

Single dose of 2000 mg/kg bw

No. of animals per sex per dose:

Two groups of three females were dosed.

Control animals:

no

Details on study design:

- Dosing procedure: Initially, three females (Group 1) were dosed, and then based on the observations a further group of three females (Group 2) were dosed.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> Body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

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 occured

Clinical signs:

other: Treatment at the dose level of 2000 mg/kg bw caused vocalisation (3/6), hunched back (6/6), irritability (3/6). Group 1 was symptom free from 6 hours after the treatment and Group 2 was symptom free from one day after the treatment. See Table 1 for result

Gross pathology:

There was no evidence of any gross findings at a dose level of 2000 mg/kg bw.

Any other information on results incl. tables

Table 1: Clinical Observations

Group No.	Animal No.	Observation	Observation Time													Frequency
			30 min	1 h	2 h	3 h	4 h	6 h	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7-14
1	8897	Symptom Free	-	-	-	-	-	+	+	+	+	+	+	+	+	15/20
		Vocalisation	+	+	+	-	-	-	-	-	-	-	-	-	-	3/20
		Irritability	1	1	-	-	-	-	-	-	-	-	-	-	-	2/20
		Hunched Back	+	+	+	+	+	-	-	-	-	-	-	-	-	5/20
	8898	Symptom Free	-	-	-	-	-	+	+	+	+	+	+	+	+	15/20
		Vocalisation	+	+	-	-	-	-	-	-	-	-	-	-	-	2/20
		Irritability	1	1	-	-	-	-	-	-	-	-	-	-	-	2/20
		Hunched Back	+	+	+	+	+	-	-	-	-	-	-	-	-	5/20
	8899	Symptom Free	-	-	-	-	-	+	+	+	+	+	+	+	+	15/20
		Vocalisation	+	+	-	-	-	-	-	-	-	-	-	-	-	2/20
		Irritability	1	1	-	-	-	-	-	-	-	-	-	-	-	2/20
		Hunched Back	+	+	+	+	+	-	-	-	-	-	-	-	-	5/20
2	8900	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	+	14/20
		Hunched Back	+	+	+	+	+	+	-	-	-	-	-	-	-	6/20
	8901	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	+	14/20
		Hunched Back	+	+	+	+	+	+	-	-	-	-	-	-	-	6/20
	8902	Symptom Free	-	-	-	-	-	-	+	+	+	+	+	+	+	14/20
		Hunched Back	+	+	+	+	+	+	-	-	-	-	-	-	-	6/20

+ = present; - = absent

Frequency of observations = number of occurance of observation/ total number of observations

Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Market/Large/Many

Table 2: Body Weight

Group No.	Animal No.	Body weight (g) Day				Body Weight Gain (g) Days
		-1	0	7	14	-1 - 0	0 - 7	7 - 14	-1 - 14
1	8897	223	208	235	265	-15	27	30	42
	8898	223	210	229	242	-13	19	13	19
	8899	215	202	226	244	-13	24	18	29
2	8900	218	211	237	245	-7	26	8	27
	8901	211	202	244	249	-9	42	5	38
	8902	205	195	228	234	-10	33	6	29
Mean:		215.8	204.7	233.2	246.5	-11.2	28.5	13.3	30.7
Standard Deviation:		7.1	6.1	6.8	10.3	3.0	8.0	9.5	8.2

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw

Executive summary:

The acute oral toxicity of the test material was determined in a GLP study conducted in line with OECD 423, EU Method B.1 tris and EPA OPPTS 870.110, according to the acute toxic class method. A total of six fasted female Wistar rats were exposed to the test material at 2000 mg/kg bw by oral gavage. Individuals were observed for mortality, clinical signs of toxicity, bodyweight gain and then submitted for necropsy 14 days after exposure. Initially, three female animals were treated with the test material at 2000 mg/kg bw. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guideline. Under the conditions of the test no mortality was observed, individual weight gain showed no signs of treatment related effects, and t here was no evidence of any gross findings at necropsy. Clinical signs were observed in some individuals, vocalisation (3/6), hunched back (6/6), irritability (3/6). However, Group 1 was symptom free from 6 hours after the treatment and Group 2 was symptom free from one day after the treatment. Based on these observations the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female Wistar rats.