Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) was considered based on different experimental studies conducted on rats and mice, the LD50 values were considered to be >5000 mg/kg bw in rat and 6450 mg/kg bw in mice. The studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

The given test chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) has very low vapour pressure (6.41E-13 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

Acute Dermal toxicity dose (LD50) for target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) was considered based on experimental study conducted on rats, the value was considered to be >2000 mg/kg bw. The study concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) cannot be classified for acute dermal toxicity.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from handbook
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Acute oral toxicity of 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (CAS no.: 61789-40-0) in rat.
GLP compliance:
not specified
Test type:
other: OECD Guideline 401 (Acute Oral Toxicity)
Limit test:
yes
Specific details on test material used for the study:
- IUPAC Name: 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts- Common Name: Cocamidopropyl Betaine- Smiles: CCCCCCCCCCCC(=O)NCCCN{+} (C)(C)CC(=O)O{-}- Molecular formula :C19H38N2O3- Molecular weight :342.52 g/mole- Substance type:Organic- Physical state:Solid- Purity:31% active ingredient
Species:
rat
Strain:
other: CD [Crl:COBS CD (SD) BR] rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Weight at study initiation: Body weights ranged between 110 and 150 gm
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Total = 10 (per sex per dose: 5)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: Animals were observed immediately after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation. Individual body weights were recorded on days 1, 8 and 15. - Necropsy of survivors performed: yes, all animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs, when present, was recorded.
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was observed at 5000 mg/kg bw
Clinical signs:
Signs of reaction to treatment observed in all rats shortly after dosing were: piloerection and increased salivation. Piloerection persisted throughout Day 1 and was accompanied on Day 2 by abnormal body carriage (hunched posture) and diarrhea. Recovery, as judged by external appearance and behavior, was advanced by Day 3 (piloerection alone) and complete by Day 4.
Body weight:
Slightly low body weight gains were recorded for 4 males and 3 females on Day 8. All rats achieved anticipated body weight gains during the second week of the study.
Gross pathology:
Terminal autopsy findings were normal.
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
Acute oral toxicity dose (LD50) value was considered to be >5000 mg/kg (>1500 mg/kg active ingredient), when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) via oral route.
Executive summary:

Acute oral toxicity study was conducted according to OECD guideline 401 by using test chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts(Cocamidopropyl Betaine) (CAS no.: 61789-40-0) in 10 male and female CD rats at the dose concentration of 5000 mg/kg bw. The given test chemical (31% active ingredient) was administered via oral route.Animals were observed immediately after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation. Individual body weights were recorded on days 1, 8 and 15. Necropsy of survivors was performed. All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs, when present, was recorded.No mortality was observed at 5000 mg/kg bw. Signs of reaction to treatment observed in all rats shortly after dosing were: piloerection and increased salivation. Piloerection persisted throughout Day 1 and was accompanied on Day 2 by abnormal body carriage (hunched posture) and diarrhea. Recovery, as judged by external appearance and behavior, was advanced by Day 3 (piloerection alone) and complete by Day 4. Slightly low body weight gains were recorded for 4 males and 3 females on Day 8. All rats achieved anticipated body weight gains during the second week of the study. Terminal autopsy findings were normal. Therefore, LD50 value was considered to be >5000 mg/kg (>1500 mg/kg active ingredient), when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from handbook.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity of 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (CAS no.: 61789-40-0) in rat.
GLP compliance:
not specified
Test type:
other: Acute Dermal Toxicity
Limit test:
yes
Specific details on test material used for the study:
- IUPAC Name: 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts- Common Name: Cocamidopropyl Betaine- Smiles: CCCCCCCCCCCC(=O)NCCCN{+} (C)(C)CC(=O)O{-}- Molecular formula:C19H38N2O3- Molecular weight :342.52 g/mole- Substance type:Organic- Physical state:liquid- Purity: 31% active ingredient
Species:
rat
Strain:
other: CD [Crl:COBS CD (SD) BR] rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Weight at study initiation: weighing range of 200 to 232 g prior to dosing.
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
not specifiedTEST SITE - Area of exposure: dorsolumbar region - % coverage: 10% of the total body surface - Type of wrap if used: The treated area was then promptly covered with gauze, which was held in place with an impermeable dressing encircled firmly around the trunk. REMOVAL OF TEST SUBSTANCE - Washing (if done): The dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30 - 40 °C) water and blotting dry with absorbent paper. - Time after start of exposure:24-hour
Duration of exposure:
24 hour
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Total = 10 (5 male and 5 female rats)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days - Frequency of observations and weighing: The treated areas of skin were examined daily for 14 days for signs of dermal irritation and assessed according to an arbitrary scoring system. Individual body weights of rats in the study were recorded on Days 1, 8 and 15. - Necropsy of survivors performed: yes, all animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded.
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was observed at 2000 mg/kg bw
Clinical signs:
There were no clinical signs of systemic reaction t to treatment. Sites of application of the test substance showed slight or well-defined erythema on Day 2. Well-defined erythema persisted in three male and all female rats on Day 3. There were no more intense reactions to treatment, and resolution of erythema was completed by Day 6. Slough or hyperkeratinization affected the treated skin of 4, 5, 6, 8, 9 and 10 rats on Days 4 and 5 only.
Body weight:
not specified
Gross pathology:
Terminal autopsy findings were normal.
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
Acute dermal toxicity dose (LD50) value was considered to be >2000 mg/kg bw, when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) by dermal application occlusively.
Executive summary:

Acute dermal toxicity study was conducted according to OECD guideline 402 by using test chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts(Cocamidopropyl Betaine) (CAS no.: 61789-40-0) in 10 male and female CD rats at the dose concentration of 2000 mg/kg bw. One day prior to treatment, hair was removed from the dorsolumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used. The test substance (31% active ingredient) was applied by spreading it evenly over the prepared skin. The treated area was then promptly covered with gauze, which was held in place with an impermeable dressing encircled firmly around the trunk. At the end of the 24-hour exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30 - 40 °C) water and blotting dry with absorbent paper. The treated areas of skin were examined daily for 14 days for signs of dermal irritation and assessed according to an arbitrary scoring system. Individual body weights of rats in the study were recorded on Days 1, 8 and 15. Necropsy of survivors was performed. All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded. No mortality was observed at 2000 mg/kg bw. There were no clinical signs of systemic reaction to treatment. Sites of application of the test substance showed slight or well-defined erythema on Day 2. Well-defined erythema persisted in three male and all female rats on Day 3. There were no more intense reactions to treatment, and resolution of erythema was completed by Day 6. Slough or hyperkeratinization affected the treated skin of 4, 5, 6, 8, 9 and 10 rats on Days 4 and 5 only. Terminal autopsy findings were normal. Hence, LD50 value was considered to be >2000 mg/kg bw, when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) by dermal application occlusively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 4 and from secondary source.

Additional information

Acute oral toxicity:

In different experimental studies, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine). The studies are summarized as below –

The experimental study conducted on rats and mentioned in handbook and secondary sources for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) was designed to determine acute oral toxicity. The study was conducted according to OECD guideline 401 in 10 male and female CD rats at the dose concentration of 5000 mg/kg bw. The given test chemical (31% active ingredient) was administered via oral route.Animals were observed immediately after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation. Individual body weights were recorded on days 1, 8 and 15. Necropsy of survivors was performed. All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs, when present, was recorded.No mortality was observed at 5000 mg/kg bw. Signs of reaction to treatment observed in all rats shortly after dosing were: piloerection and increased salivation. Piloerection persisted throughout Day 1 and was accompanied on Day 2 by abnormal body carriage (hunched posture) and diarrhea. Recovery, as judged by external appearance and behavior, was advanced by Day 3 (piloerection alone) and complete by Day 4. Slightly low body weight gains were recorded for 4 males and 3 females on Day 8. All rats achieved anticipated body weight gains during the second week of the study. Terminal autopsy findings were normal. Therefore, LD50 value was considered to be >5000 mg/kg (>1500 mg/kg active ingredient), when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral route.

The above experimental study is supported with the study mentioned in publication and secondary sources, for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) and conducted in groups of 5/sex/dose male and female wistar albino rats at the dose concentration of 2000, 4000, 5000, 6300, 8000 and 16000 mg/kg bw. The given test chemical (30% active ingredient) was administered via oral gavage route. Animals were observed for mortality and clinical signs for 14 days. Mortality was observed as follows, At 4000 mg/kg - 1/5 rats died on day 14; At 5000 mg/kg - 2/5 rats died 1 each on days 5 and 11; At 6300 mg/kg – 3/5 rats died, 1 each on days 4,6, and 10; At 8000 mg/kg - all 5 rats died, with deaths occurring on days 1,4 and 14; At 16000 mg/kg - all 5 rats died on day 1. Clinical signs such as, sluggishness, diarrhea, nasal hemorrhage, wetness around posterior (increased in severity with dose) was observed. Therefore, LD50 value was considered to be 4900 mg/kg, with a 95% confidence limit of 3700 to 6500 mg/kg; and 1500 mg active ingredient/kg (95% Confidence Limits = 1100-2000 mg/kg), when Groups of 5/sex/dose male and female wistar albino rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

This study is supported by the study conducted on rats and data mentioned in publication for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) in Groups of 10 (5 male and 5 female) Sprague-Dawley rats at the dose concentration of 2000, 2710, 3680, 5000, or 6780 mg/kg bw. The given test chemical (30% active ingredient) was administered via oral gavage route. Animals were observed for mortality, clinical signs and body weight changes for 15 days. Necropsy of survivors was performed. Mortality was observed as follows, At 3680 mg/kg - 2/10 rats died; At 5000 mg/kg - 6/10 rats died; and At 6780 mg/kg – 8/10 rats died within 2 to 3 days. Diarrhea was observed in rats of all treatment groups, and decreased motor activity was observed in rats of all treatment groups, except at the lowest dose. Dried blood around the nose and salivation were observed in 3 to 5 male rats of the 5000 mg/kg dosage groups. Surviving rats gained an average of 20 to 130 gm by day 15. At necropsy, a "bloodlike viscous liquid" was observed in the intestines. Therefore, LD50 value was considered to be 4910 mg/kg, with a 95% confidence limit of 4190 to 5910 mg/kg, when Groups of 10 (5 male and 5 female) Sprague-Dawley rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

All these studies are also supported by the study mentioned in same publication on rats for the target chemical Cocamidopropyl Betaine. The study was conducted in groups of 10 (5 male and 5 female) Wistar rats at the dose concentration of 5000, 6300, 7940 and 10000 mg/kg bw. The given test chemical (30% active ingredient) was administered via oral gavage route. Animals were observed for mortality for 14 days. Mortality was observed as follows, at 5000 mg/kg - 2/10 rats died, 1 died within 24 h of administration. At 7940 mg/kg – 6/10 rats died, 5 died within 24 h. At 10000 mg/kg – 8/10 rats died, 7 died within 24 h. Therefore, LD50 value was considered to be 7450 mg/kg, with a 95% confidence limit of 6480 to 8570 mg/kg, when groups of 10 (5 male and 5 female) Wistar rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

Another study supported by the study mentioned in publication and handbook for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts was conducted in groups of 10 (5 male and 5 female) Wistar rats at the dose concentration of 5000, 6300, 7940 and 10000 mg/kg bw. The given test chemical (30% active ingredient) was administered via oral gavage route. Animals were observed for mortality, clinical signs and body weight changes for 24 h. Necropsy of survivors were performed. 50% mortality was observed. Rats in all dosage groups had decreased motor activity, abnormal body posture, coordination disturbance; cyanosis, diarrhoea, and decreased body temperature beginning approximately 20 min after dosage and persisting for 24 h. Surviving rats in all groups had body weight gains of 36 to 45 g and were normal in appearance and behaviour. Redness of the stomach and intestinal mucous membrane was observed at necropsy. Mild redness of the intestinal mucous membrane was observed in the animals killed at the termination of the study. Therefore, LD50 value was considered to be 8100 mg/kg, with a 95% confidence limit of 6810 to 9640 mg/kg, when groups of 10 (5 male and 5 female) Wistar rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

The above studies are further supported by the study conducted on mice and mentioned in publication for the target chemical Cocamidopropyl Betaine. The acute oral toxicity study was conducted in groups of 10 (5 male and 5 female) CFR Carworth mice at the dose concentration of6450 (5660-7350) mg/kg bw. The given test chemical (30% active ingredient) was administered via oral gavage route.Animals were observed for mortality for 7 days. 50% mortality was observed at 6450 mg/kg bw. Therefore, LD50 value was considered to be 6450 mg/kg, with a 95% confidence limit of 5660 to 7350 mg/kg, when groups of 10 (5 male and 5 female) CFR Carworth mice were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

These studies are further supported by the study mentioned in secondary sources for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine). The study was conducted in groups of 5/sex/dose male and female wistar rats at the dose concentration of 5000, 6300, 7940 and 10000 mg/kg bw. The given test chemical (30% active ingredient) was administered via oral route. Animals were observed for mortality and clinical signs for 14 days. Necropsy of survivors was performed. Mortality was observed within day 1. Clinical signs such as, decreased motor activity, coordination disturbance, abnormal body posture, piloerection, diarrhea, decreased body temperature, (effects were observed 20 min after application, reversible after 24 h) was observed. Redness of stomach and intestinal mucus was observed. Therefore, LD50 value was considered to be 7900 mg/kg bw, when groups of 5/sex/dose male and female wistar rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral route.

Different study mentioned in secondary sources and conducted on rats for the target chemical Cocamidopropyl Betaine is supported to the above mentioned studies. Acute oral toxicity study was conducted in 5/sex/dose male and female Wistar rats at the dose concentration of 4000, 8000, 10000, 12500, 16000 or 32000 mg/kg bw. The given test chemical (30% aqueous solutions) was administered via oral gavage route. Animals were observed for mortality and clinical signs on daily basis for two weeks post-dose. No post-mortem or histopathology examinations were performed in this study. Mortality was observed as, 0/5 at 4000 mg/kg dose level (original solution); 2/5 at 8000 mg/kg dose level (original solution); 4/5 at 10000 mg/kg dose level (original solution); 5/5 at 12500, 16000 and 32000 mg/kg dose levels (original solution). Slight diarrhoea and unkempt coats were observed in animals treated with 4000 mg/kg of the test substance as an aqueous mixture. Lethargy, diarrhoea, nasal haemorrhage and unkempt coats, increasing in severity proportionately to the levels employed, were observed in all animals treated at dose levels of 8000 mg/kg (test substance as an aqueous mixture) and above. Therefore, LD50 value was considered to be 2600 mg active ingredient/kg (95% Confidence Limits = 1800-3600 mg active ingredient/kg) and 8550 mg/kg bw, original solution (30% aqueous), when5/sex/dose male and female Wistar rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

This study is supported with the data mentioned in secondary source for the target chemical Cocamidopropyl Betaine and was conducted in mice at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when mice were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral route.

All the above experimental studies are contradicted with the study mentioned in secondary sources for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts(Cocamidopropyl Betaine) (CAS no.: 61789-40-0). The acute oral toxicity study was conducted according toOECD guideline 401by using test chemical in 10 male and female Sprague-Dawley rats at the dose concentration of 1800 mg/kg bw. The given test chemical (335.61% active) was given as undiluted and administered via oral gavage route. All animals were weighed prior to dosing and at termination. Animals were observed frequently on the day of dosing and for 14 days subsequent to dosing. Necropsy of survivors was performed. All animals that died during the study were subjected to a gross necropsy. All 5 females died by Day 2 (one day after dosing). All females exhibited salivation, diarrhoea, ataxia, and/or decreased activity prior to death. The males exhibited similar clinical signs as the females on Days 1 (day of dosing) and 2; however, all animals recovered by Day 3. Hence, LD50 value was considered to be >1800 mg/kg bw, when 10 male and female Sprague-Dawley rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) via oral gavage route.

From all the above experimental studies, maximum number of studies concluded that the LD50 value is >2000 mg/kg bw, with detailed and reliable data. Thus, comparing this value with the criteria of CLP regulation, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

The given test chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) has very low vapour pressure (6.41E-13 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

In different studies, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) along with the studies available on the structurally similar read across substances. The studies are summarized as below –

The experimental study conducted on rats and mentioned in secondary sources for the target chemical 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) was designed to determine acute dermal toxicity dose. The study was conducted according to OECD guideline 402 in 10 male and female CD rats at the dose concentration of 2000 mg/kg bw. One day prior to treatment, hair was removed from the dorsolumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used. The test substance (31% active ingredient) was applied by spreading it evenly over the prepared skin. The treated area was then promptly covered with gauze, which was held in place with an impermeable dressing encircled firmly around the trunk. At the end of the 24-hour exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30 - 40 °C) water and blotting dry with absorbent paper. The treated areas of skin were examined daily for 14 days for signs of dermal irritation and assessed according to an arbitrary scoring system. Individual body weights of rats in the study were recorded on Days 1, 8 and 15. Necropsy of survivors was performed. All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded. No mortality was observed at 2000 mg/kg bw. There were no clinical signs of systemic reaction to treatment. Sites of application of the test substance showed slight or well-defined erythema on Day 2. Well-defined erythema persisted in three male and all female rats on Day 3. There were no more intense reactions to treatment, and resolution of erythema was completed by Day 6. Slough or hyperkeratinization affected the treated skin of 4, 5, 6, 8, 9 and 10 rats on Days 4 and 5 only. Terminal autopsy findings were normal. Hence, LD50 value was considered to be >2000 mg/kg bw, when 10 male and female CD rats were treated with 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) by dermal application occlusively.

The above experimental study is supported with the study available on the structurally similar read across substance and mentioned in study report. The study was designed and conducted to determine the acute dermal toxicity profile of test chemical in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that given test chemical does not classify as an acute dermal toxicant.  CLP Classification: “Not classified”.

These studies are further supported with the study mentioned in study report for the data available on the structurally similar read across substance. The reported study was designed and conducted to determine the acute dermal toxicity profile of test chemical in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

Thus, based on the above studies on 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine)(CAS no.: 61789-40-0) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing these values with the criteria of CLP regulation, 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., hydroxides, inner salts (Cocamidopropyl Betaine) cannot be classified for acute oral and dermal toxicity. For acute inhalation toxicity wavier were added so, not possible to classify.