N-[2-[bis(carboxymethyl)amino]ethyl]-N-(1-oxononyl)Glycine

Endpoint summary

Description of key information

In an acute oral toxicity study conducted according to OECD TG 423, the LD50 cut-off in rats was determined to be 5000 mg/kg bw (unclassified). 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2022-05-02 to 2022-09-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot/batch number of test material: LFND3B1003
- Purity: 100% (HPLC)
- Expiry Date: August 2025

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: store in a cool place, protected from light and moisture

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Test item was dissolved in corn oil. The dose formulations were made shortly before each dosing occasion. Homogeneity of the test item in the vehicle was maintained by vortexing the prepared solution thoroughly before each dose administration.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: step 1: 8–9 weeks; step 2: 9–10 weeks; step 3: 8-9 weeks
- Weight at study initiation: step 1: 158–163 g; step 2: 173–177 g; step 3: 174–185 g
- Fasting period before study: 17 to 18 hours (access to water was permitted)
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: step 1: 7 days; step 2: 14 days; step 3: 7 days under laboratory conditions

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

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): lot no. MKCP9878

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 300 mg/kg body weight, as recommended in the OECD TG 423.

Doses:

Step 1: 300 mg/kg bw
Step 2: 2000 mg/kg bw
Step 3: 2000 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: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15. A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Necropsy of survivors performed: yes; all animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.
- Clinical signs including body weight: Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

The test item showed no mortality and no acute oral toxicity characteristics after a single dose administration at a dosage of 300 mg/kg bw and 2000 mg/kg bw.

Clinical signs:

other:

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Other findings:

None of the animals showed weight loss during the observation period. The body weight development of all animals was within the expected range.

For individual results see box "Any other information on results incl. tables".

Table 1: Absolute Body Weights in g and Body Weight Change in %

Step	Animal No./Sex	Starting Dose (mg/kg bw)	Body Weight (g)			Body Weight Change in Comparison to Day 1 [%]
			Day 1	Day 8	Day 15
1	1/Female	300	163	188	200	23
	2/Female		158	176	190	20
	3/Female		160	191	204	28
2	4/Female	2000	177	202	215	21
	5/Female		177	197	208	18
	6/Female		173	202	214	24
3	7/Female	2000	174	196	214	23
	8/Female		185	222	230	24
	9/Female		176	202	207	18

 

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, no signs of toxicity or mortality were observed and the median lethal dose of N-[2-(bis(carboxymethyl)amino]ethyl]-N-(1-oxononyl)Glycine after a single oral administration to female rats, observed over a period of 14 days is unclassified (LD50 cut-off = 5000 mg/kg bw).

Executive summary:

In an acute oral toxicity study according to OECD 423, fasted young female Wistar rats/group were given a single dose N-[2-(bis(carboxymethyl)amino]ethyl]-N-(1-oxononyl)Glycine (100% purity) dissolved in corn oil. One group of three female rats was treated with the test item by oral gavage administration at a starting dosage of 300 mg/kg body at a dose volume of 10 mL/kg. No compound related mortality was recorded for any animals of this step. Based on these results and according to the acute toxic class method regime, two groups, each of three female rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. No compound related mortality was recorded for any animal of step 2 and 3.

All animals survived until the end of the study. No clinical findings were observed in any of the animals. None of the animals showed weight loss during the observation period. No specific gross pathological changes were recorded for any animal.

In this study, a LD50 cut-off = 5000 mg/kg bw (unclassified) was determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study with the test item N-[2-(bis(carboxymethyl)amino]ethyl]-N-(1-oxononyl)Glycine in fasted young female Wistar rats according to OECD 423, no compound related mortality, clinical findings, body weight effects or pathological signs was recorded at doses of 300 and 2000 mg/kg bw/day.

Based on this study, a LD50 cut-off = 5000 mg/kg bw (unclassified) was determined.

Justification for classification or non-classification

Based on the available study results, classification of N-[2-[bis(carboxymethyl)amino]ethyl]-N-(1-oxononyl)glycine for acute toxicity is not warranted in accordance with CLP Regulation (EC) No 1272/2008.