title: Safety assessment of enzyme-containing personal cleansing products: exposure characterization and development of IgE antibody to enzymes after a 6-month use test.
abstract: BACKGROUND
  Enzyme-containing personal cleansing products were being considered for the consumer market. Although enzymes have been marketed safely for many years as ingredients in laundry products, their use in a personal cleansing application represented a new type of exposure for consumers that was not supported by the historical safety data. An exposure assessment and additional safety data would be needed before marketing to ensure consumer safety.
  
  
  OBJECTIVE
  The work in this paper was designed to evaluate the potential for inhalation exposure to the enzyme during use of this new product while showering. Then a clinical trial was conducted to determine whether or not the level, duration, and routes of exposure encountered during use of this product would induce a Type I sensitization response to the enzyme.
  
  
  METHODS
  Exposure was assessed during normal showering activities by collecting air samples with both high volume and personal samplers and quantitating enzyme levels with an ELISA. To assess the potential for sensitization, panelists were asked to use a prototype protease-containing bar product for all personal cleansing tasks and to keep a use diary reporting any associated symptoms. Physical and dermatologic examinations and skin prick tests with enzyme were conducted before the test commenced and at 2-month intervals.
  
  
  RESULTS
  Exposure assessment results showed that airborne enzyme levels were primarily dependent on the concentration of the enzyme in the personal cleansing product. Mean values for total airborne enzyme protein ranged from 5.7 to 11.8 ng/m3 when enzyme concentration, time of use, and measurement technique remained constant. After 6 months of at-home product use, four of 61 test subjects using the enzyme-containing bar had positive skin prick test responses when tested with the enzyme. The skin prick test data were supplemented with serologic analyses, which detected IgE specific for the protease enzyme. None of these subjects showed any clinical symptoms indicative of allergic reaction.
  
  
  CONCLUSIONS
  The ability of enzymes to induce development of allergic antibodies in this study led to the conclusion that this prototype enzyme-containing personal cleansing bar would represent an inappropriate use of enzymes in a consumer product application. The likelihood of both induction of an immunologic response and subsequent elicitation of allergy symptoms in a small but significant fraction of the user population was high. This finding resulted in the decision to halt further development of this prototype.
authors.affiliation: Procter & Gamble Company, Cincinnati, Ohio 45253-8707, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Kelling
authors.forename: R G
authors.initials: RG
authors.lastname: Bartolo
authors.forename: K D
authors.initials: KD
authors.lastname: Ertel
authors.forename: L A
authors.initials: LA
authors.lastname: Smith
authors.forename: D D
authors.initials: DD
authors.lastname: Watson
authors.forename: K
authors.initials: K
authors.lastname: Sarlo
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000209:etiology* / Q000276:immunology; D003902:Detergents / Q000009:adverse effects* / Q000737:chemistry; D010450:Endopeptidases / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D010865:Pilot Projects; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D012882:Skin Tests; D013997:Time Factors
chemical_list: D000336:Aerosols; D001426:Bacterial Proteins; D003902:Detergents; D007073:Immunoglobulin E; D010450:Endopeptidases