(carboxylatomethyl)dodecyldimethylammonium

Endpoint summary

Description of key information

From the surrogate data available, this substance does not appear to exhibit acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Only very limited documentation, only 5 days observation period

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Physical state: liquid, aqueous solution
- Analytical purity: 30% a.i.
- Composition of test material, percentage of components: 30 % active (C8-18 with majority in C12-14), 7 % sodium chloride, 63 % water
- Lot/batch No.: 26R-259.
The members of the alkyl betaines category are amphoteric surfactants containing a quaternary ammonium ion and a carboxylic structure. They are referred to as inner salts due to their zwitterionic character. They are all manufactured from natural materials such as vegetable oils and can vary in chain length from C8 to C18. They are generally marketed as aqueous solutions (20 - 40 %).
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected.
The Cosmetic Ingredient Review Expert Panel reviewed the product use, formulation and safety data of eleven alkyl betaines, as used in cosmetics. (Final report issued 2014-04-04)
The Panel concluded that the common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group.

Species:

mouse

Strain:

CF-1

Sex:

not specified

Details on test animals or test system and environmental conditions:

- Source: Charles River
- Weight at study initiation: 18 - 21 g
- Fasting period before study: no data
- Housing: 5/cage
- Diet (e.g. ad libitum): Lab Blox, ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

- Concentration in vehicle: 10 % (test material was diluted 1:3 in water just prior to the test)

Doses:

6670, 8350, 10000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days
- Necropsy of survivors performed: no data

Statistics:

Oral LD50 was calculated according to the method of Litchfield and Wilcoxon (1949).

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 640 mg/kg bw

Based on:

act. ingr.

95% CL:

>= 2 310 - <= 3 000

Remarks on result:

other: recalculated to neat substance

Mortality:

10000 mg/kg: 7/10
8350 mg/kg: 4/10
6670 mg/kg: 1/10

Clinical signs:

other: not reported

Gross pathology:

not reported

Interpretation of results:

GHS criteria not met

Conclusions:

Cocoalkyldimethylbetaine has a similar structure to lauryl betaine.This is considered to be a good surrogate substance for the lauryl betaine being registered.
Further animal testing cannot be justified.

Executive summary:

The members of the alkyl betaines category are amphoteric surfactants containing a quaternary ammonium ion and a carboxylic structure.

Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected. The Cosmetic Ingredient Review Expert Panel reviewed the product use, formulation and safety data of eleven alkyl betaines, as used in cosmetics. (Final report issued 2014-04-04). The Panel concluded that the common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group.

Reference 2

Endpoint:

acute toxicity: oral

Data waiving:

study waived due to provisions of other regulation

Justification for data waiving:

other:

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Single dose, 14 day observation

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

EPA review of data
Study performed on non-phosphated form
Results used to help confirm biological equivalence for read across

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

other: Old LD50 protocol

Limit test:

no

Specific details on test material used for the study:

The members of the alkyl betaines category are amphoteric surfactants containing a quaternary ammonium ion and a carboxylic structure. They are referred to as inner salts due to their zwitterionic character. They are all manufactured from natural materials such as vegetable oils and can vary in chain length from C8 to C18. They are generally marketed as aqueous solutions (20 - 40 %).
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected.
The Cosmetic Ingredient Review Expert Panel reviewed the product use, formulation and safety data of eleven alkyl betaines, as used in cosmetics. (Final report issued 2014-04-04)
The Panel concluded that the common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group.
This is considered to be a good surrogate substance for the substance being registered.
Further animal testing cannot be justifed.

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

Dose levels based on actives; 1200 mg/kg - 10 000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 500 mg/kg bw

Based on:

act. ingr.

Mortality reported at highest concentrations

No pathology reported

Interpretation of results:

GHS criteria not met

Conclusions:

The members of the alkyl betaines category are amphoteric surfactants containing a quaternary ammonium ion and a carboxylic structure. They are referred to as inner salts due to their zwitterionic character. They are all manufactured from natural materials such as vegetable oils and can vary in chain length from C8 to C18. They are generally marketed as aqueous solutions (20 - 40 %).
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected.
The Cosmetic Ingredient Review Expert Panel reviewed the product use, formulation and safety data of eleven alkyl betaines, as used in cosmetics. (Final report issued 2014-04-04)
The Panel concluded that the common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group.
Cocamidopropyl betaine is considered to be a good surrogate substance for the substance being registered.
Further animal testing cannot be justifed.
(Note - HPV reports indicate other acute toxicity tests and although some variation in results, it is concluded that the substance need not be classified as harmful)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 hours on occluded skin

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Remarks:

No details given in the review report.

Test type:

standard acute method

Specific details on test material used for the study:

94.9% pure

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Groups of 5 male Sprague-Dawley rats received the test material dermally on clipped trunks; test sites were occluded for 24 h, after which the test sites were wiped clean of the test material

Duration of exposure:

24 hours

Doses:

not specified

No. of animals per sex per dose:

5

Control animals:

not specified

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 16 other: g/kg

Based on:

test mat.

Clinical signs:

other: Erythema, edema, desquamation, necrosis, and scab formation observed on test sites for test material, as was sluggishness and reddish nasal and ocular discharges; body weight gains within normal parameters; no treatment-related changes due to either test

Interpretation of results:

GHS criteria not met

Conclusions:

Cetyl betaine is not harmful by skin absorption.
Lauryl betaine has a very similar structure to cetyl betaine, the only difference being in the chain length of the alkyl grouping, i.e. C16 9cetyl) vs C12 (lauryl).
The CIR panel concluded that 'The common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group'

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

24 hours exposure; 14 day observation

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

US EPA source considered reliable
Test performed on analogue substance; Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected between this test material and cetyl betaine.
Although headline result is LD50 > 2 g/kg, it is uncertain if this relates to the active or to a diluted test material.
However, the EPA have judged the result as 'valid without restrictions' and cited 2 g/kg.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Limit test

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Source not specified. Activitiy not specified (not known if test material was a diluted form)

Species:

rat

Strain:

CD-1

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg (assumed actives)

No. of animals per sex per dose:

Five

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

other: Local irritation

Gross pathology:

No adverse effects on termination

Interpretation of results:

GHS criteria not met

Conclusions:

Local irritation, but this resolved during the observation periods
Although headline result is LD50 > 2 g/kg, it is uncertain if this relates to the active or to a diluted test material.
However, the EPA have judged the result as 'valid without restrictions' and cited 2 g/kg.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Specific details on test material used for the study:

30 – 35.5 % aqueous solution.
Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected between this test material and cetyl betaine.

Species:

rat

Strain:

not specified

Sex:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

study cannot be used for classification

Conclusions:

The acute toxicity of cocamidopropyl betaine (30 – 35.5 % aqueous solutions) in rats is low, with a dermal LD50 value greater than 2000 mg/kg bw.
The active ingredient level is ca. 600 mg/kg/bw but since the test does not appear to have been taken to a higher level of active ingredient, this value cannot be used for classification.

Reference 4

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The members of the alkyl betaines category are amphoteric surfactants containing a quaternary ammonium ion and a carboxylic structure.

Because of the structural and functional similarities and comparable physico-chemical properties these inner salts and sodium salts, a similar ecotoxicological and toxicological profile can be expected. The Cosmetic Ingredient Review Expert Panel reviewed the product use, formulation and safety data of eleven alkyl betaines, as used in cosmetics. (Final report issued 2014-04-04). The Panel concluded that the common core chemical structure, similar functions and concentrations in cosmetics, and the predicted physicochemical properties enabled grouping these ingredients and reading across the available toxicological data to support the safety assessment of each individual compound in the entire group.