1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-coco 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:

27 February, 1990 - 15 March, 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 401 compliant), the test guideline being in force at the time of the study but deleted in 2002 and substituted by other test guidelines (not up-to-date).

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:

3-(3-Cocoamido-propyl)-dimethylammonium-2-hydroxypropansulfonate

Cas Number:

68139-30-0

IUPAC Name:

3-(3-Cocoamido-propyl)-dimethylammonium-2-hydroxypropansulfonate

Constituent 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

Test material form:

liquid

Details on test material:

Light yellow, clear, slightly viscous liquid.

Commercial products covered by the composition:
- MACKAM CBS 50GE = aqueous solution at 36.3% w/w of active content (= surface-active fraction); aqueous solution at 49.5% w/w of solids (= REACH registered UVCB);
- MACKAM CBS 50G = aqueous solution at 42% w/w of active content (= surface-active fraction); aqueous solution at 50% w/w of solids (= REACH registered UVCB);
- REWOTERIC AM = aqueous solution at 42% w/w of active content (= surface-active fraction); aqueous solution at 50% w/w of solids (= REACH registered UVCB);
- REWOTERIC AM-CAS = aqueous solution at 42% w/w of active content (= surface-active fraction); aqueous solution at 50% w/w of solids (= REACH registered UVCB);
- BETADET SH-R = aqueous solution at 41.5% w/w of active content (= surface-active fraction).

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: No data.
- 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): No data.
- Water (e.g. ad libitum): No data.
- Acclimation period: at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2.
- Humidity (%): 50-85.
- Air changes (per hr): No data.
- Photoperiod (hrs dark / hrs light): 12 / 12 (7.00 am-7.00 pm).

IN-LIFE DATES: No data.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

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

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.

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:

GHS criteria not met

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.