Registration Dossier

Administrative data

Description of key information

Betaine has not been found to be an irritant or corrosive in any in vitro or in vivo tests performed. Betaine has also been tested in well prepared and conducted studies, resembling OECD TG 404 performed on humans for skin irritation. Eye irritation testing was performed by executing OECD TG405 study in accordance with GLP. In vitro testing of skin absorption resulted in extremely low permeation, 0.1%.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from NOV 19 2006 to FEB 4 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well designed and executed study for percutaneous absorption (permeation potential) of betaine in vitro using Franz chambers with freshly isolated human epidermis (abdominal skin). This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Qualifier:
equivalent or similar to
Guideline:
other: OECD 428
Deviations:
yes
Remarks:
only one dose (5%) was used as duplicate, intead of series but two different vehicles were used.
Principles of method if other than guideline:
Franz chambers: donor and receiver chamber filled with PBS. Atop betaine (5% in saline or emulsion, pH7.4. Completely solubilized) was applied, samples were withdrawn from receiver chamber at appropriate intervals and analysed.
GLP compliance:
no
Species:
other: Human freshly isolated abdominal epidermis
Strain:
not specified
Type of coverage:
other: In vitro: Franz chambers (donor/receiver)
Preparation of test site:
other: In vitro: freshly isolated human epidermis clamped between cell halves
Vehicle:
physiological saline
Remarks:
or emulsion
Controls:
not required
Duration of treatment / exposure:
24 hours
Observation period:
1,2,4,6,8,11 and 24 hours
Number of animals:
in vitro
Irritation / corrosion parameter:
other: percutaneous permeation/absorption (in vitro diffusion study using Franz chambers) at 1, 2, 4, 6, 8, 11 and 24 hours
Value:
ca. 0
Remarks on result:
other:
Remarks:
extremely low permeation, 0,1% of the initial dose regardless of formulation
Other effects / acceptance of results:
Percutaneous permeation of betaine was extremely low. Less than 0.1 % of the initial dose applied atop the skin permeated through the skin regardless of the formulation.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was tested for percutaneous absorption using Franz chambers with a protocol similar to OECD guideline 428. The test was designed and performed adequately. The result show that the test substance has an extremely low percutaneous permeation capability.
Executive summary:

The test substance was tested for percutaneous absorption using Franz chambers with a protocol similar to OECD guideline 428. The results showed that betaine has an extremely low percutaneous permeation capability (0.1% of the initial dose regardless of formulation). Therefore, the test substance considered not irritating under the conditions of this test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 OCT 1991 to 25 OCT 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: Albino
Vehicle:
water
Remarks:
10% w/v solution
Controls:
other: The untreated eye served as control.
Amount / concentration applied:
0.1 mL of 10% solution
Duration of treatment / exposure:
single dose
Observation period (in vivo):
1, 24, 48, and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Animals were examined under a standard light source designed to comply with the requirements of BS 950 Part 1 (Artificial Daylight for the Assessment of Colour). The eyes were assessed for damage or irritation to the cornea, iris and conjunctiva using the untreated eye as a control.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
No signs of irritation or corneal or iridial lesions were observed in any of the animals throughout the 72-hour observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The application of betaine (natural extract AP, 10% w/v in distilled water) did not result in any ocular irritation, and it can be considered non-irritant at the concentration used in this study.
Executive summary:

Betaine was tested in an in vivo eye irritation study according to OECD guideline 405. The application of betaine (natural extract AP, 10% w/v in distilled water) did not result in any ocular irritation, and it can be considered non-irritant at the concentration used in this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Betaine has been widely used in cosmetics because of its anti-irritant properties and its favourable effects on skin health as an anti-irritant. Multiple studies have been conducted on humans to study the effects. Respiratory sensitisation has not been tested since the physical state along with particle size, hygroscopic properties and vapour pressure provide information that betaine cannot cause concern for respiratory irritation.

Justification for classification or non-classification

Skin irritation: Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, as irritant / corrosive: based on testing on skin sensitisation and irritation on animals and humans.

 

Eye irritation: Not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, based on eye irritation testing on animals.