1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C12-14(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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: US Guideline: Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, FDA, 1959

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

Study performed before implementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18(even numbered) and C18 unsaturated acyl) derivs., hydroxides, inner salts

EC Number:

931-333-8

Cas Number:

147170-44-3

Molecular formula:

not applicable

IUPAC Name:

1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18(even numbered) and C18 unsaturated acyl) derivs., hydroxides, inner salts

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:

solid - liquid: aqueous solution

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Age: no data
- Sex: males and females
- Weight at study initiation: females: 150 - 170 g, males: 175 - 210 g
- Housing: individual housing in a battery of cages
- Diet: ad libitum, standardised laboratory diest Ssniff/Intermast
- Water: ad libitum
- Fasting period before study: 16 hours

ENVIRONMENTAL CONDITIONS:
- Roomtemperature: 22 +/- 1° C
- Relative humidity: 45 - 55 %
- Illumination: 12 hours daily

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

applied volumes: 0.75 - 2.1 ml/animal (depending on individual body weight and designated dose level)
Test substance was applied in the original state (aqueous solution, a.i. according to producer information 30 %) as delivered by the sponsor.

Doses:

5.0, 6.3, 7.94, 10.0 ml/kg bw, test substance applied as delivered by the sponsor (30 % a.i.)

No. of animals per sex per dose:

5 females
5 males

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 d
- Body weights were recorded before treatment (day 0) and after 14 days (animals which survived)
- Clinical observation: In each animal a number of clinical-toxicological signs were evaluated. Any change from the normal condition was noted and degree of severity of any clinical symptoms was assessed. The animals were examined at the following post-treatment intervals: 20 min, 1 h, 3 h, 24 h, 7 d, 14 d.
- Necropsy of the survivors performed: yes
- Other examinations performed: necropsy on died animals

Statistics:

Method of determining LD 50: according to Litchfield & Wilcoxon in combination with Gauß Integral

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

after 14 d

Effect level:

2 335 mg/kg bw

Based on:

act. ingr.

95% CL:

1 944 - 2 571

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Remarks:

after 14 d

Effect level:

7.45 mL/kg bw

Based on:

test mat.

95% CL:

6.48 - 8.57

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Remarks:

after 24 h

Effect level:

8.1 mL/kg bw

Based on:

test mat.

95% CL:

6.82 - 9.64

Effect levels 4

Sex:

male/female

Dose descriptor:

LD50

Remarks:

after 24 h

Effect level:

2 430 mg/kg bw

Based on:

act. ingr.

95% CL:

2 046 - 2 892

Mortality:

Number of deaths at each dose:
- 5 ml/kg bw: 2/10 (1 animal died within 24 h, 1 animal died within 48 h)
- 6.30 ml/kg bw: 2/10 (within 24 h)
- 7.94 ml/kg bw: 6/10 (5 animals died within 24 h, 1 animal died within 48 h)
- 10 ml/kg bw: 8/10 (7 animals died within 24 h, 1 animal died within 4 days)

Clinical signs:

other: >= 5 ml/kg bw: decreased motor activity, coordination disturbances, abnormal body posture, piloerection, diarrhoea, skin/mucosa cyanosis, decreased body temperature with dose-dependant increase of effects. Clinical signs were observed at 20 minutes, 1

Gross pathology:

- Decedents: reddened gastric and intestinal mucosa
- Animals sacrificed at study termination 14 days p.a.: light reddened intestinal mucosa

Any other information on results incl. tables

LD50 values reported by the study authors refer to the test substance as specified above (30 % a.i.): 7.45 (6.48 - 8.57) ml/kg after 14 days and 8.10 (6.81 - 9.64) ml/kg after 24 hours

Density of the substance: roughly 1 g/cm3.
LD50 (14 day) referring to 100 % active substance: 2235 mg/kg bwLD50 (24 hours) referring to 100 % active substance: 2430 mg/kg bw 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single oral administration, the oral LD50 was determined to be 7.45 ml/kg bodyweight based on product, corresponding to 2335 mg/kg bw active ingredient.

Executive summary:

In an acute oral toxicity study according to US Guideline Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, FDA, 1959, which is comparable to the OECD guideline 401 (1981), 5 male and 5 female Wistar rats were given a single oral dose of Coco AAPB (30 % a.i.) as delivered by the sponsor at doses of 5.0, 6.3, 7.94, and 10.0 ml/kg bw. Animals were then observed for 14 days.

At 5.0, 6.3, 7.94, and 10.0 ml/kg bw 2/10, 2/10, 6/10, and 8/10 animals died, respectively. Most animals died within 24 hours p.a.. Weight gains were normal in all animals. Clinical signs at >= 5 mL/kg bw were decreased motor activity, coordination disturbances, abnormal body posture, piloerection, diarrhoea, skin/mucosa cyanosis and decreased body temperature with dose response realtionship. At >= 7.94 mL/kg bw animals showed prone position. Clinical signs were observed at 20 minutes, 1 h and 3 h after application. Except of slight diarrhoea in one animal in dose groups 6.3, 7.94 and 10 mL/kg bw, each, all symptoms were reversible after 24 hours. 7 days after application, all surviving animals were free of clinical symptoms. Gross pathology examination of animals found dead revealed reddened gastric and intestinal mucosa. Animals sacrificed at study termination 14 days p.a. had light reddened intestinal mucosa.

Oral LD50 Combined =  7.45 mL/kg bw after 14 d

Oral LD50 Combined =  8.1 mL/kg bw after 24 h

LD50 determined refers to the test substance as delivered by the sponsor. There is no information on content of active ingredient of the test substance in the study report. However, according to producer information tested Coco AAPB has 30% active ingredient. The density is roughly 1 g/mL. Therefore the calculated oral LD50 combined referring to 100 % active substance = 2335 mg/kg bw after 14 d

Coco AAPB is of low toxicity based on the LD50 in males and females.