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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 vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 APR 1989 to 19 APR 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The studies were well prepared and conducted, resembling OECD TG 404 for the irritation scoring and the methods parts, except where humans were used instead of animals. The number of humans was significantly larger than the number of animals required by TG 404. 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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
other species: human
GLP compliance:
yes
Species:
human
Strain:
not specified
Details on test animals and environmental conditions:
26 healthy human volunteers of both sex between 16 and 65 years of age. They reported no allergies to common consumer products and had not taken part in a skin test on the same site during the last three months. Each volunteer was required to give their written informed consent before taking part.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: several different vehicles
Controls:
yes
Amount / concentration applied:
Large dose of betaine (5%) in several different vehicles with corresponding negative controls.
Duration of treatment / exposure:
48 hour occlusive patch test: 24h initial contact period and second 24h period (fresh patch)
Observation period:
After 24h and after 48h
Number of animals:
26 healthy human volunteers.
Details on study design:
The test materials were applied to the upper outer arm under occlusion for an initial contact period of 24 hours. Patches were then removed and the skin reaction was assessed one hour later using a numerical scoring system. Immediately after assessment, an identical fresh patch was applied to the same skin site for further 24 hours and skin reactions were again examined one hour after removal. The test and control samples were applied to adjacent sites on the outer surface of the upper arm occlusive aluminum Finn chamber. The Finn chambers are concave aluminum discs providing a test area of 50mm^2 with a diameter of 8mm and volume of 25 microliters. They are arranged in rows on Scaupor non-occlusive surgical tape at a standard spacing of 1cm.

The test and control samples were applied by immersing Whatman 3mm filter paper discs in the product and applying the saturated discs to the Finn chambers using forceps. The completed patch assembly was held in position on the arm by means of the Scanpor backing tape.

After 24 hours patches were removed and the degree of skin irritation was assessed one hour later by a trained assessor using a numerical scoring system outlined below. An identical fresh patch was applied to the same site immediately after assessment by aligning the new patch with ink marks on the skin. The second patch was removed after further 24 hours and test sites were again assessed one hour later.

All assessments were carried out under standard lighting conditions by an assessor who was not aware which sample had been applied to each skin site.

Method of Assessment: in order to assess the degree of irritancy several signs symptomatic of skin irritation and their severity were noted using the scoring system
0 = no visible relevant reaction
1 = reaction just present
2 = slight reaction
3 = moderate reaction
4 = severe reaction

the signs of irritation were awarded different ratings of significance as follows.
Sign / Abbreviation / Rating
Vesicles / V / 5
Oedema / Oe / 4
Erythema / R / 3
Flakiness / F / 2
Dryness / D / 1
Wrinkling / W / 1
Glazing / G / 1

In order to obtain a numerical value for the total reaction at each site, the severity score for each sign was multiplied by the rating. The resulting values were summed to give a total score for the degree of irritation at that site.

The skin irritation scores for the test and control products were compared statistically using the binomial probability test.
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 26 human volunteers
Time point:
other: 24 hours
Score:
ca. 1
Reversibility:
fully reversible
Remarks on result:
other: the slight irritant effect is seen also in control groups
Irritant / corrosive response data:
Sample / Mean skin irritation scores 24 hours / Mean skin irritation scores 48 hours
1. Marbert Deodorant (Control) / 0.96 / 1.04
2. Marbert Deodorant + 5% Betafin AP / 0.65 / 1.12
3. Rexona Antiperspirant (Control) / 0.62 / 1.35
4. Rexona Antiperspirant + 5% Betafin AP / 1.35 / 1.85
5. Clearasil (Control) / 1.5 / 2.12
6. Clearasil + 5% Betafin AP / 1.27 / 1.50
7. Boots Eau de Cologne (Control) / 1.15 / 1.88
8. Boots Eau de Cologne + 5% Betafin AP / 1.46 / 1.65
9. Insignia After Shave Lotion (Control) / 1.45 / 1.54
10. Insignia After Shave Lotion + 5% Betafin AP / 0.85 / 1.23

Individual scores were subjected to statistical analysis using the binomial probability test. Results of the analysis indicated the following, significance probability, p<0.05.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of this test, addition of Betafin AP 5% to the Clearasil product significantly reduced the irritancy of the sample. This effect was not reflected, however, in the results obtained from the other test samples.

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

Since betaine does not have sensitising or irritating properties the study was designed to assess the anti-irritant properties of betaine in common skin care products. The results indicate that in the majority of samples tested addition of 5% Betafin AP made little difference to the irritancy of the product. The irritancy of the Clearasil sample was, however, significantly reduced by addition of Betafin AP. The Clearasil control was the most irritant sample tested, and as it contains surfactant, it may be that this contributed to the irritancy. The effect of adding Betafin AP would therefore be to reduce the irritancy of the surfactant of the surfactant component.

 

The irritancy of the Rexona Antiperspirant sample actually appeared to be enhanced by the addition of Betafin AP but this effect was only significant at 24 hours. In the absence of detailed information on the product formulae it is not easy to explain the observed effects but it would seem likely that the anti-irritant effect property of Betafin AP is related to its water binding properties.

 

Under the conditions of this test, addition of Betafin AP 5% to the Clearasil product significantly reduced the irritancy of the sample. This effect was not reflected, however, in the results obtained from the other test samples.

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:
other: OECD TG405 study following GLP standards. 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:
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
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
>= 0
Max. score:
0
Reversibility:
fully reversible
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
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.

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
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 the EU Directive 67/548/EEC and 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 the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, based on eye irritation testing on animals.