Science in the box

P&G scientists adopt a stepwise approach in testing for skin safety. The stepwise approach starts with an assessment of all available skin effects data, then moves to benchmarking with previous testing data before testing is done with volunteer panellists (starting with small control groups and then leading to larger numbers in more realistic use situations).

Stepwise Testing for Safety Assessments
Our commitment to the skin safety of all our products, and our stepwise approach to ensuring that safety, has been detailed in a number of publications by Procter & Gamble scientists. Our approach is consistent with the highest industry standards, such as outlined by the European Association of the Soap & Detergent Industry (A.I.S.E.) (see our A.I.S.E. pages).

We use a stepwise approach to ensure the skin safety and compatibility of our products. The approach starts with an evaluation of all available skin effects data on each component of the formulation from our previous testing and from the scientific literature. The ingredients and concentrations for the proposed formulation are then compared to our large number of historical product formulations to determine which products may be similar in composition and, therefore, similar in their safety profile. These similar, historical formulations serve as benchmarks for the new product in the course of the testing programme.

Skin safety test results on the historical formulations, along with information on each formulation component, allow the toxicologist to develop an interim safety assessment so that careful testing can proceed with the help of volunteer panellists.

A large number of testing protocols have been developed specifically for laundry detergents. Some of them have been published by company scientists (check our publication database for further scientific material).

All of these tests rely on some exaggeration of concentration and/or duration of normal exposures, i.e., those exposures that a consumer might have during normal product use.

Initial tests are done under highly controlled conditions using small numbers of panellists. As our experience grows with the particular product formulation, the exposures approach more normal product use with larger numbers of panellists. In most of these tests, the new product is compared side-by-side with the benchmark formulation.

A variety of skin irritation studies have been conducted on volunteers under conditions that exaggerate the exposures to laundry detergents. The results demonstrate that P&G laundry detergents and fabrics laundered in P&G detergents are not irritating to the skin.

Single Application Patch Test









Single Application Patch Tests are short-term tests conducted to confirm that a product is not a skin irritant even under highly exaggerated exposure conditions. In the single application patch test, undiluted test material is moistened and applied to the upper arm using a small patch (smaller than the pad of a standard plaster). The patch stays in place for 4 hours, then the test site is observed for signs of irritation over the next 3 days. If the test material is irritating, the patch site will appear red, and may appear to be dry or rough. Typically, a minimum of 12 volunteer panellists will participate in a single test.

3-Patch Application Test (3-PAT)

A 3-Patch Application Test (3-PAT) is conducted to confirm that the product will not be irritating with exposures of even longer duration. The 3-Patch Application Test (3-PAT) is commonly used for this purpose. The exposure conditions of the 3-PAT are highly exaggerated over any exposure that would be encountered in real-life circumstances. Therefore, it is considered a very rigorous test of the potential to cause irritation.

In the 3-PAT, a dilution of the test material is applied to the upper arm using a small patch, and left in place for 24 hours and removed. After a 24 hour recovery period, it is replaced by a fresh patch. This is repeated for a total of 3 applications (i.e., three 24 hour applications in a five day period). The test site is observed for signs of irritation throughout the test, and 24 hours after removal of the final patch. If the test material is irritating, the patch site will appear red, and may appear to be dry or rough. Typically, 12 volunteer panellists are used in the 3-PAT.

Result: We tested 8 liquid products in the 3-PAT. All products caused very slight irritation reactions, which is consistent with our historical data for products that are considered to be very mild to skin. We also conducted the test using fabric swatches that had been laundered in a liquid detergent to confirm that detergent residue on the laundered fabrics is non-irritating. The laundered fabric swatches did not cause irritation in the 3-PAT.

21-Day Cumulative Irritation Test

This test was developed as a means of evaluating any irritant effects that may be cumulative with repeated exposure. In this test, small swatches of fabrics are laundered in detergent formulations. These are applied to the upper arms of panellists five times a week for three weeks. Each application stays in place for 24 hours. The sites are observed for signs of irritation throughout the test. If the test material is irritating, the patch site will appear red, and may appear to be dry or rough.

Result: Fabric laundered in a liquid detergent was tested using 33 volunteer panellists. The fabric was only slightly irritating. This slight irritation is attributed to constant shutting off of the skin for a prolonged period of time and a result that is consistent with our historical data for products that are considered to be very mild to skin.

Wrist Band Wear Test













This test simulates wearing a tight-fitting garment. (Bannan, et al, 1992) In this test, swatches of knitted cotton are laundered in the detergent and placed around the wrists of volunteer panellists using a tight fitting athletic wrist band. These are kept in place for 6 hours per day on 4 consecutive days. The skin is evaluated for signs of irritation 24 hours after each application of the test material. Normally, 15 volunteer panellists are used for this type of study.

Hand Immersion Test





This test involves prolonged, repeated soaking of the hands in detergent solution to simulate and/or exaggerate the type of exposure that occurs when a detergent is used for hand laundry (Suskind, et al, 1963). This test can involve 12-64 volunteer panellists, depending on the number of products being tested. One hand is immersed in a solution of the test product, while the other is immersed in a solution of a product for which the mildness and skin safety profile are very well known. Products can be tested at the expected hand laundry use concentration (0.1-0.5%), or at concentrations 5-10 times higher than expected use. Hands are immersed in solutions 30 minutes per day for 4 consecutive days. The condition of the hands and nails are evaluated each day.

Result: We evaluated 6 liquid product solutions (at 0.75%) and 2 powder products (at 0.5%). There were no signs of irritation.

References

• Bannan, E. A., J. F. Griffith, T. L. Nusair, L. J. Sauers. 1992. Skin testing of laundered fabrics in the dermal safety assessment of enzyme-containing detergents, Journal of Toxicology - Cutaneous and Ocular Toxicology, 11:327-339.
• Suskind, R. R., M. M. Meister, S. R. Scheen, D. J. A. Rebello. 1963. Cutaneous effects of household synthetic detergents and soaps, Archives of Dermatology, 88:117-124.

 

Human Repeat Insult Patch Test (HRIPT)

For decades, the Human Repeat Insult Patch Test (HRIPT) has been used worldwide to determine if a material has the potential to cause contact sensitization or skin allergies (Stotts, 1980). In the HRIPT, a small patch of the test material (smaller than the pad of a standard plaster) is applied for 24 hours to the upper arm of each of 80 to 100 volunteer panellists. The material is reapplied three times a week for three weeks at the same site on the upper arm. After a two week rest period, the test material is applied again at the same site. If the test material causes a contact allergy, the test site will appear red, and may be slightly swollen or itchy.

Result: Thirteen HRIPTs have been conducted on our current detergent formulations. These tests involved a total of 1221 volunteer panellists. There was no indication that any or our formulations caused skin allergies. This was the expected result for the finished product formulation since none of the individual ingredients have been shown to cause skin allergies when used in our laundry detergents.

Simulated Laundry Pre-treatment Test with Diagnostic Patch Test

The exposure in this test is designed to simulate and exaggerate the types of exposures a consumer might have if she uses a concentrated product to pre-treat stains. In this test, a 50% slurry of powder product is used. The volunteer panellists rub their hands with this slurry for 60 seconds, three times each week for 8 weeks. A 48-hour diagnostic patch test for contact sensitization is conducted prior to the first exposure, and following the final exposure to determine if this rigorous exposure to the product produced any evidence of contact sensitization (skin allergy).

Result: There was no evidence that exposure to the laundry powder product used in this test produced skin allergy in any of the volunteers.

References
• Stotts J., "Planning, conduct and interpretation: Human predictive sensitization patch tests," in Current Concepts in Cutaneous Toxicity, V. A. Drill and P. Lazar, Eds. (Academic Press, New York, 1980), pp. 41-53.

P&G scientists have conducted long-term home use tests to evaluate the potential of a detergent to cause either skin irritation or skin allergy with realistic product exposures.

Home Usage Test

This type of test is based on realistic exposures to the product, and can evaluate the potential of the product to cause either irritation or sensitization (allergy). It has been described in several P&G publications (Rodriguez, et al. 1994 and Bannan, et al. 1992).

Volunteer panellists are assigned to one of two groups. In phase one, one group uses a test laundry detergent in place of their normal detergent for a period of six weeks. The other group uses a different product. At the end phase one, the panellists switch products. This eliminates bias in the study. In addition to normal laundry use, panellists are asked to use the product for hand laundering and stain pre-treatment at least once a week for the duration of the test. The skin condition of the panellists is assessed for each product and compared with historical data on products with a well defined skin safety and mildness profile.

A professional assessment of the skin condition confirmed that our products did not cause skin irritation or skin allergy.

References:

• Rodriguez C., G. Calvin, C. Lally, J. M. LaChapelle. 1994. Skin effects associated with wearing fabrics washed with commercial laundry detergents, Journal of Toxicology - Cutaneous and Ocular Toxicology, 13:39-45.
• Bannan, E. A., J. F. Griffith, T. L. Nusair, L. J. Sauers. 1992. Skin testing of laundered fabrics in the dermal safety assessment of enzyme-containing detergents, Journal of Toxicology - Cutaneous and Ocular Toxicology, 11:327-339.

Biological detergents (detergents containing enzymes) have been tested for skin irritation, skin sensitization (allergies) and skin effects under various conditions and across different continents. Results show that detergents with enzymes have the same excellent skin compatibility profile as so-called non-biological products.

3-Patch Application Test (3-PAT)

The 3-PAT is commonly used to evaluate irritation with repeated exposures. We compared biological and non-biological products side-by-side. Each of four laundry products was tested at 0.25%: a non-biological compact powder, a biological compact powder, a non-biological liquid and a biological liquid.

Results: The biological products did not produce more irritation than the non-biological products, confirming that the addition of enzymes to a detergent formulation does not result in an increase in the skin irritation caused by profile of the detergent.

Home Usage Tests

This type of test is based on realistic exposures to the product, and can evaluate the potential of the product to cause either irritation or sensitization (allergy). It has been described in several P&G publications (Rodriguez, et al. 1994 and Bannan, et al. 1992). The general test design is for volunteer panellists to use the test product in place of their usual laundry detergent for all home laundry.

Usage Test in Homes with Toddlers
For this test, volunteer panellists with at least one child of age 4 or less in the family were allowed to participate. Volunteer panellists were assigned to one of two groups. In phase one, one group used a biological laundry detergent in place of their normal detergent for a period of 6 weeks. The other group used a non-biological product. At the end phase one, the panellists switched product for another 6 week home use phase. Skin evaluations were conducted every 3 weeks. In addition, diagnostic patch testing was conducted at the beginning and the end of the study to detect contact sensitization (skin allergy).
Results: In our test on laundry products, 111 families participated. There were no differences in skin condition during use of product with enzyme versus product without enzymes. Furthermore, there was no evidence of contact sensitization among any panellists or family members. These results confirmed that
Home Usage Tests in Mexico

In Mexico, 65% of consumers perform all laundry tasks exclusively by hand. The remainder use a combination of hand and machine laundry. In addition, over 90% of consumers use the same detergent product for both hand laundry and washing dishes. Therefore, consumers in Mexico typically have much greater skin exposure to laundry products than consumers in Europe and North America.

We conducted two home usage tests in Mexico. In the first test (a two week test), a biological powder detergent was compared to a non-biological product currently on the market in Mexico. The 502 volunteer panellists used each product for 2 weeks. The condition of the panellists’ skin after using each product was evaluated by a dermatologist after using each product. In addition, the panellists were asked to rate the mildness of each product.

Results: The dermatologist's evaluation indicated that the biological product was milder to skin than the non-biological product. The panellists’ rating showed a similar result. Thus, the results of the two week test confirm that enzymes do not have an adverse effect on the mildness of the detergent product.

In a second home usage test (a four week test), 311 volunteer panellists compared two different biological detergent formulations.

Results: The skin evaluations gave no indication of any adverse skin effects due to either product, confirming that biological detergent formulations are mild under the extreme use conditions common in Mexico.

Home Usage Test in Venezuela

We conducted a three week home usage test in Venezuela where, like Mexico, hand laundry is the norm. The test compared two biological powder detergents: one had a higher level of enzyme compared to the other with different enzyme levels. The 223 volunteer panellists used each product for 3 weeks. The condition of the panellists’ skin after using each product was professionally evaluated after using each product. In addition, the panellists were asked to rate the mildness of each product.

Results: There were no significant irritant or other adverse skin effects from either product, confirming that an increase in the level of enzymes does not have a harmful or negative effect on the mildness of the product.

Home Usage Test with Diagnostic Patch Test in Morocco

In Morocco, the normal laundry practice is for consumers to mix their laundry powder with a small amount of water to make a highly concentrated slurry or paste of the product. This is applied directly to clothes by hand, resulting in skin exposure to a high concentration of the laundry product ingredients.

The total duration of the home usage in the test in Morocco was 12 weeks. For the first 6 weeks, the 142 volunteer panellists laundered clothes in a controlled test facility using a concentrated paste of a powder product containing enzymes. For the next 6 weeks, panellists used the product at home as they would normally use their regular laundry detergent. A diagnostic patch test for contact sensitization (skin allergy) was conducted prior to the start of the test, and after completion of the test. The skin condition was evaluated at the start, after the first 6 weeks and at the completion of the test.

Results: After 12 weeks of use under these extreme conditions there was no evidence of adverse skin effects either in the objective evaluation or in the panellists’ comments. In addition, there was no evidence of contact sensitization (skin allergy).

References
• Suskind, R. R., M. M. Meister, S. R. Scheen, D. J. A. Rebello. 1963. Cutaneous effects of household synthetic detergents and soaps, Archives of Dermatology, 88:117-124.

Testing with human volunteers must follow certain quality standards and ethical guidelines. P&G researchers apply Good Clinical Practice (GCP) standards in all of their clinical trials and tests. Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, performing, monitoring, auditing, recording, analysis and reporting trials that involve human subjects. Compliance with GCP assures that the rights, safety, and well-being of trial subjects are protected and that the clinical trial data are credible. This International Conference on Harmonization (ICH) guidance provides a unified standard for the European Union, Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in those jurisdictions. GCP is codified by FDA (Food and Drug Administration) in 21CFR50, 56. Underpinning the GCP regulation is the requirement for all human research to be approved by an Institutional Review Board/Ethics Committee (IRB/EC). The sole charge of the IRB/EC is to protect the rights of human research subjects, assuring that 1) the study protocol is well designed to provide meaningful data, 2) the risk to the health of the subject is justified relative to the benefit of the knowledge to be gained by the research, 3) that research subjects are not coerced into participating, i.e., participation is purely voluntary, and 4) that each potential subject is fully informed in writing of the a) intent of the research, b) the potential risks of the research, c) full knowledge of their rights, and d) telephone numbers to call for help in the event of an adverse event or if they have any questions regarding the study or their subject rights.

The following is link to the FDA document

http://www.gpo.gov/fdsys/pkg/CFR-2001-title21-vol1/pdf/CFR-2001-title21-vol1.pdf (pages 282 and 294)