1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C12-18(even numbered) acyl) derivs., hydroxides, inner salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

other: OECD test guideline 401 ‘Acute Oral Toxicity’ deleted on 17th December 2002

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide

Molecular formula:

C16H34N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxooctyl)amino]propyl]ammonium hydroxide

Constituent 2

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C18H38N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxodecyl)amino]propyl]ammonium hydroxide

Constituent 3

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide

EC Number:

242-893-1

EC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxododecyl)amino]propyl]ammonium hydroxide

Cas Number:

19223-55-3

Molecular formula:

C20H42N2O5S

IUPAC Name:

N-[3-(dodecanoylamino)propyl]-2-hydroxy-N,N-dimethyl-3-sulfopropan-1-aminium hydroxide

Constituent 4

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C22H46N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxotetradecyl)amino]propyl]ammonium hydroxide

Constituent 5

Reference substance name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide

Molecular formula:

C24H50N2O5S

IUPAC Name:

(2-hydroxy-3-sulphopropyl)dimethyl[3-[(1-oxohexadecyl)amino]propyl]ammonium hydroxide

Constituent 6

Reference substance name:

[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide

EC Number:

264-390-6

EC Name:

[2-hydroxy-3-sulphopropyl]dimethyl[3-[(1-oxooctadecyl)amino]propyl]ammonium hydroxide

Cas Number:

63663-12-7

Molecular formula:

C26H54N2O5S

IUPAC Name:

2-hydroxy-N,N-dimethyl-N-[3-(stearoylamino)propyl]-3-sulfopropan-1-aminium hydroxide

Constituent 7

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

impurity 1

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

sodium chloride

impurity 2

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

impurity 3

Reference substance name:

Disodium 2-hydroxypropane-1,3-disulfonate

Molecular formula:

C3H8O7S2.Na2

IUPAC Name:

Disodium 2-hydroxypropane-1,3-disulfonate

impurity 4

Reference substance name:

Sodium (±)-2,3-dihydroxypropanesulphonate

EC Number:

252-542-4

EC Name:

Sodium (±)-2,3-dihydroxypropanesulphonate

Cas Number:

35396-47-5

Molecular formula:

C3H8O5S.Na

IUPAC Name:

sodium (±)-2,3-dihydroxypropanesulphonate

impurity 5

Reference substance name:

Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

EC Number:

930-947-3

IUPAC Name:

Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: not provided
- Weight at study initiation: 171-276 g (males), 164-216 g (females)
- Fasting period before study: from 16 hours before until 3-4 hours after administration
- Housing: up to a maximum of 5 rats per cage (Macrolon type III cage)
- Diet (e.g. ad libitum): not detailed
- Water (e.g. ad libitum): not detailed
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50-85
- Air changes (per hr): not detailed
- Photoperiod (hrs dark / hrs light): 12 / 12 (7.00 am-7.00 pm)

IN-LIFE DATES: Not provided

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
No vehicle used (solution administered as such with different dosing volumes)

MAXIMUM DOSE VOLUME APPLIED:
1000 mg/kg: 2.33 mL/kg bw
2000 mg/kg: 4.65 mL/kg bw
3000 mg/kg: 6.98 mL/kg bw

Doses:

1000, 2000 and 3000 mg active component/ kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Examinations performed: mortality (over the 24-hour post-dosing period, and then daily), clinical signs (daily), body weights (just before dosing, on days 7 and 14)
- Necropsy of survivors performed: yes

Statistics:

The method of Finney D.Y., Probit Analysis (3rd ed., Cambridge, 1971) was used for calculating the oral LD50.

Results and discussion

Preliminary study:

One animal died within 24 hours of dosing at 2000 mg/kg

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Remarks on result:

other: Could not be calculated because only at the high dose pre-terminal deaths were lower than 100% and higher than 0%

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 020 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: at 24 h and 14 days after dosing

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 950 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: at 24 h and 14 days after dosing

Mortality:

See table below

Clinical signs:

other: Up to 3 days post-dosing, reduced general activity was observed at 3000 mg/kg, together with squatting position, reduced skin turgor, cyanosis, diarrhea and piloerection on some occasions.

Gross pathology:

- 2000 and 3000 mg/kg: animals killed in extremis within 24 hours post-dosing showed hemorrhagic and lytic alterations in the gatro-intestinal tract and/or yellow-orange discoloration of lungs and/or reddish pelvis at macroscopic examination.
- At terminal sacrifice (14 days post-dosing): no test-article abnormalities noted at necropsy.

Any other information on results incl. tables

Dose (mg/kg)	Post-treatment time
	Males			Females
	24 hours	7 days	14 days	24 hours	7 days	14 days
1000	0/5	0/5	0/5	0/5	0/5	0/5
2000	0/5	0/5	0/5	2/5	2/5	2/5
3000	3/5	3/5	3/5	2/5	2/5	2/5

Cumulative Mortality over the 14-day observation period

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The oral LD50 in rats was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively, at 24 hours and 14 days after administration. The oral LD50 in male rats could not be calculated because deaths occurred only in the high-dose group.

Executive summary:

Cocamidopropyl hydroxysultaine, as a 42% aqueous solution, has been tested for acute oral toxicity in Wistar rats. The test article was administered as such using different dosing volumes to reach the desired dose levels. Three groups of 5 rats per gender received a dose volume of 2.33, 4.65 and 6.98 mL/kg, equivalent to 1000, 2000 and 3000 mg active ingredient/kg, respectively. Examinations for mortality and clinical signs were performed daily during the 14-day study period. Body weights were measured just before dosing, and 7 and 14 after dosing. A macroscopic examination was performed at the necropsy of survivors on day 14.

 

A high incidence of pre-terminal deaths occurred at 2000 and 3000 mg/kg, whereas no death occurred at 1000 mg/kg: 3/5 male rats were found dead or sacrificed in extremis within 24 hours of dosing in the 3000 mg/kg dose group, and 2/5 female rats were found dead or sacrificed in extremis within 24 hours of dosing in each of the 2000 mg/kg and 3000 mg/kg dose groups. Marked clinical signs, such as general reduced activity together with diarrhea, squatting position, piloerection and/or reduced skin turgor were observed at 3000 mg/kg within 3 days post-dosing. Body weight gain was normal in surviving animals over the observation period. Hemorrhagic and lytic mucous membrane alterations in the gastro-intestinal tract, considered test-article related, were observed at necropsy in animals found dead or sacrificed in extremis within 24 hours of dosing in the 2000 mg/kg and 3000 mg/kg dose groups. At terminal sacrifice, no test-related macroscopic findings were observed in the other animals.

The oral LD50 in rats was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively, at 24 hours and 14 days after administration. The oral LD50 in male rats could not be calculated because deaths occurred only in the high-dose group.