1-Propanaminium, 2-hydroxy-N-(2-hydroxyethyl)-N-methyl-N-[2-[(1-oxo-9-octadecen-1-yl)amino]ethyl]-3-sulfo-, methyl sulfate, sodium salt (1:1:1)

Endpoint summary

Description of key information

acute oral: The LD50 in female rats is reported to be >2000 mg/kg bw.

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:

21 May 2018 - 18 June 2018

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:

17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in house bred, Animal Facility, Bioneeds India Private Limited Devarahosahally, Sompura Hobli, Nelamangala Taluk, Bangalore Rural District, PIN - 562 111, Karnataka, India
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 160.39 g to 176.55 g
- Housing: max. 3 animals per cage in standard polypropylene cage
- Diet: ad libitum, Altromin Maintenance diet for rats and mice 1324 manufactured by Altromin Spezialfutter GmbH & Co. KG
- Water: ad libitum, deep bore-well water passed through reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.6 to 22.9°C
- Humidity: 43 to 65%
- Air changes: 12 to 15 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Step I 30 mg/mL and Step II 200 mg/mL
- Amount of vehicle: 0.5% w/v Carboxy Methyl Cellulose (CMC)
- Justification for choice of vehicle: 0.5% w/v CMC is universally accepted and routinely used vehicle in oral toxicity studies.

Doses:

300 mg/kg bw (Step I) and 2000 mg/kg bw (Step II)

No. of animals per sex per dose:

3 females per Step and dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) post dosing on Day 1 and at least once daily thereafter for clinical signs of toxicity throughout the
experimental period. Individual animal body weight was recorded at receipt, on day 1 before test item administration and on day 8 and 15 during the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, observations included changes in skin, fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern

Statistics:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In Step-I and Step-I confirmation, the animals were dosed with 300 mg/kg body weight. No mortality was observed.
In Step-II and Step-II confirmation, the animals were dosed with 2000 mg/kg body weight. No mortality was observed.

Clinical signs:

other: No clinical sigsns were observed.

Gross pathology:

No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the experiment, it is concluded that the LD50 for the test item is > 2000 mg/kg body weight when administered as a single dose by oral gavage to female Sprague Dawley rats.

Executive summary:

The test item was evaluated for acute oral toxicity in Sprague Dawley rats according to OECD Guideline No. 423: Acute Oral Toxicity - Acute Toxic Class Method adopted on 17 December 2001. A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as there was no available information on the LD50 of the test item.

A total of 12 females (3 females each for each Step-I, Step-I confirmation, Step-II and Step-II confirmation) were used for the experiment. All then animals of Step-I and Step-I confirmation were administered with 300 mg/kg body weight of the test item and Step II and Step II confirmation were administered with 2000 mg/kg body weight of the test item by oral route.

All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Body weight was recorded on day 1 before test item administration and on day 8 and 15 during the observation period. At the end of observation period, all the surviving animals were sacrificed under carbon dioxide anaesthesia, subjected to necropsy and gross pathological examination.

In Step-I and Step-I confirmation, the animals dosed with 300 mg/kg body weight did not reveal any clinical signs of toxicity and mortality. In Step-II and Step-II confirmation, the animals dosed with 2000 mg/kg body weight did not reveal any clinical signs of toxicity and mortality.

No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg and 2000 mg/kg body weight. All the animals revealed physiologically normal increase in the body weight.

No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according OECD TG 423

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

Oral

The test item was evaluated for acute oral toxicity in Sprague Dawley rats according to OECD Guideline No. 423: Acute Oral Toxicity - Acute Toxic Class Method adopted on 17 December 2001. A starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight as there was no available information on the LD50 of the test item.

A total of 12 females (3 females each for each Step-I, Step-I confirmation, Step-II and Step-II confirmation) were used for the experiment. All then animals of Step-I and Step-I confirmation were administered with 300 mg/kg body weight of the test item and Step II and Step II confirmation were administered with 2000 mg/kg body weight of the test item by oral route.

All the animals were observed for clinical signs of toxicity and mortality at 30 to 40 min, 1 hr (±10 min), 2 hrs (±10 min), 3 hrs (±10 min) and 4 hrs (±10 min) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Body weight was recorded on day 1 before test item administration and on day 8 and 15 during the observation period. At the end of observation period, all the surviving animals were sacrificed under carbon dioxide anaesthesia, subjected to necropsy and gross pathological examination.

In Step-I and Step-I confirmation, the animals dosed with 300 mg/kg body weight did not reveal any clinical signs of toxicity and mortality. In Step-II and Step-II confirmation, the animals dosed with 2000 mg/kg body weight did not reveal any clinical signs of toxicity and mortality.

No changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg and 2000 mg/kg body weight. All the animals revealed physiologically normal increase in the body weight.

No gross pathological changes were observed in any of the animals dosed at 300 mg/kg and 2000 mg/kg body weight. Based on the results of the experiment, it is concluded that the LD50 for the test item is > 2000 mg/kg body weight when administered as a single dose by oral gavage to female Sprague Dawley rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test substance is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) No 2019/521.