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

Endpoint summary

Description of key information

Acute toxicity 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

supporting study

Justification for type of information:

Refer to the section 13 of the IUCLID dataset for details on the read across justification. The acute toxicity: oral study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
- Source: Bantin & Kingman Ltd., Grimston, Aldborough, Hull, U.K.
- Age at study initiation: 5-8 weeks
- Weight at study initiation: male: 120-145g; female: 120-137g
- Fasting period before study: overnight immediately before dosing and for approximately two hours after dosing
- Housing: in groups of 5 by sex in polypropylene cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
Environmental conditions
- Temperature (°C): 20-24
- Humidity (%): 51-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Maximum volume applied: 1.94 mL/kg bw

Doses:

Single dose of 2000 mg/kg bw

No. of animals per sex per dose:

10 (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once a day; and body weights were recorded on day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: No evidence of systemic toxicity was noted during the study period.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study.

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:

A study was conducted to determine the acute oral toxicity of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 401, in compliance with GLP. Male and female Sprague-Dawley rats were administered the test substance by oral gavage at a dose of 2000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There were no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Safepharm Laboratories Limited, 1989a). Read-Across justification is attached in chapter 13.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Refer to the Read Across Justification document provided in IUCLID6 Section 13. The acute toxicity: oral study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary. The strucutre is analogue, only difference neutralization cation but being usually potassium salt more toxic than sodium and being the substance subjected to dissociation under environmental conditions, absorption, distribution, metabolism and excretion so that the influence of the counterion is eliminated, the Read Across proposed is fully justified.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

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

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.

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.

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

 

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:

Source used for the test is the same as target, only neutralized with potassium instead of sodium.Toxicological properties are not influenced by these two cations.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. Read-Across justification is attached in chapter 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Rationale for reliability incl. deficiencies:

other: Read Across Study that can be used as a result of structural similarity

Justification for type of information:

Refer to the section 13 of the IUCLID dataset for details on the read across justification. The acute toxicity: dermal study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Species:

rat

Strain:

other: Crl:WI (Han) SPF

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On clipped skin (dorsal and dorso-lateral parts of the trunk)
The application area covered at least 10% of the total body surface area

Duration of exposure:

24 hours
The animals were then observed for 14 days.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

According to guideline

Statistics:

According to guideline

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Other findings:

A very slight edema (grade 1) was observed.

Conclusions:

Under the study conditions, the acute dermal LD50 of the substance in rats was determined to be >5000 mg/kg bw.

Executive summary:

A Read-Across analogue approach was used to evaluate dermal acute toxiciy. A study was conducted to determine the acute dermal toxicity of the read-across substance L-glutamic acid, N-coco-acyl derivs., disodium salts according to OECD Guideline 402, in compliance with GLP. Male and female Crl:WI (Han) SPF rats were exposed 5000 mg/kg bwof the test substance to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 h. The application area covered at least 10% of the total body surface area. The animals were observed for 14 d. No mortality occurred during the study. No signs of systemic toxicity were observed. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals did not adequately increase during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study but a very slight edema (grade 1) was observed. Under the study conditions, the acute dermal LD50 of the substance in rats was determined to be >5000 mg/kg bw (BASF SE, 2013). Read Across justification is attached in chapter 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Oral:

A study was conducted to determine the acute oral toxicity of the read-across substance L-glutamic acid, N-coco acyl derivs., monosodium salts according to OECD Guideline 401, in compliance with GLP. Male and female Sprague-Dawley rats were administered the test substance by oral gavage at a dose of 2000 mg/kg bw. Following administration, the animals were observed for 14 d and mortality, clinical signs and body weights were recorded daily. At the end of this period, rats were examined for macroscopic and microscopic abnormalities. There were no mortality in this study. No evidence of systemic toxicity was noted during the study period. No toxicologically significant effects on bodyweight were recorded during the study period and no abnormalities were seen at necropsy of animals killed at the end of the study. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be >2000 mg/kg bw (Safepharm Laboratories Limited, 1989a). The acute oral toxicity of the test material was also 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. This study was done on same molecule as target but neutralized with potassium. As Potassium salts are usually more toxic than sodium and being the substance subjected to dissociation under environmental conditions, absorption, distribution, metabolism and excretion so that the influence of the counterion is eliminated, the Read Across proposed is fully justified. 

Inhalation:

Waiver

Dermal:

A study was conducted to determine the acute dermal toxicity of the read-across substance L-glutamic acid, N-coco-acyl derivs., disodium salts according to OECD Guideline 402, in compliance with GLP. Male and female Crl:WI (Han) SPF rats were exposed 5000 mg/kg bwof the test substance to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 h. The application area covered at least 10% of the total body surface area. The animals were observed for 14 d.No mortality occurred during the study. No signs of systemic toxicity were observed. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals did not adequately increase during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study but a very slight edema (grade 1) was observed. Under the study conditions, the acute dermal LD50 of the substance in rats was determined to be >5000 mg/kg bw (BASF SE, 2013).

Justification for classification or non-classification

Based on the acute oral toxicity and the acute dermal toxicity studies with the read-across substance L-glutamic acid, N-coco acyl derivs., disodium salt, the substance does not warrant classification for acute toxicity according to EU CLP (1272/2008) classification.