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Exposure related observations in humans: other data

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Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Type of study / information:
Skin irritation
Endpoint addressed:
skin irritation / corrosion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 404
Deviations:
yes
Remarks:
humans were used instead of animals. The number of humans was significantly larger than the number of animals required by TG 404.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Betaine monohydrate (Product name: Betafin AP) was mixed with common, slightly irritative personal care products in order to study (anti-)irritant properties of betaine.

1. Marbert Deodorant (Control)
2. Marbert Deodorant + 5% Betafin AP
3. Rexona Antiperspirant (Control)
4. Rexona Antiperspirant + 5% Betafin AP
5. Clearasil (Control)
6. Clearasil + 5% Betafin AP
7. Boots Eau de Cologne (Control)
8. Boots Eau de Cologne + 5% Betafin AP
9. Insignia After Shave Lotion (Control)
10. Insignia After Shave Lotion + 5% Betafin AP
Samples 1-6 were received from the sponsor on 29th March, 1989. Samples 7-10 were supplied by Toxicol Laboratories.

Method

Ethical approval:
other: Each volunteer was required to give their written informed consent before taking part.
Details on study design:
The test materials were applied to the upper outer arm under occlusion to 26 healthy human volunteers 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 50 mm^2 with a diameter of 8 mm and volume of 25 microliters. They are arranged in rows on Scaupor non-occlusive surgical tape at a standard spacing of 1 cm. The test and control samples were applied by immersing Whatman 3 mm 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.
Exposure assessment:
not specified
Details on exposure:
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

Results and discussion

Results:
The overall irritation score for the mean of the 26 human volunteers at 24 hours was ca. 1 and was fully reversible. The slight irritant effect was also observed in the control groups.

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.

Applicant's summary and conclusion

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.
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.