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Biomedical subjects

H L Ritz

Publications and source records attributed to H L Ritz.

14 recordsLinked to original sources
PubMed1997

Respiratory allergenicity of detergent enzymes in the guinea pig intratracheal test: association with sensitization of occupationally exposed individuals.

A guinea pig intratracheal test was used to set occupational operating guidelines for new enzyme proteins used in the detergent industry. In these studies, animals were intratracheally dosed with different levels of enzyme protein and sera from the animals were titered for allergic antibody to the enzyme. The amount of antibody produced to an enzyme was compared to the amount of antibody produced to the same protein doses of Alcalase, for which effective operating guidelines exist. These comparisons were used to determine if a new enzyme was more potent, less potent, or equivalent to Alcalase; operating guidelines were then established for the new enzyme. Termamyl was about 10-fold more potent than Alcalase and the protease subtilisin B was shown to be less potent. Another protease, Savinase, was shown to be equivalent in potency to Alcalase. The operating guidelines for Termamyl were adjusted lower, whereas the operating guidelines for the proteases were set the same as that of Alcalase. Under these conditions, we would predict that sensitizations to new enzymes would be comparable to or lower than the sensitizations to Alcalase. Prospective evaluation of skin prick test data of factory workers showed that sensitizations to Termamyl and Savinase were similar to sensitizations to Alcalase. The sensitizations to subtilisin B were lower than those to Alcalase. During this time period (7 years), only three respiratory incidents (rhinitis) were reported, demonstrating that employees with positive skin prick tests can continue to work. These comparisons indicate that the guinea pig intratracheal test is a good animal model for evaluating enzymes as respiratory allergens and that the data generated can be used to set operating guidelines for occupational allergens.

Amylases↗
PubMed1997

Proteolytic detergent enzymes enhance the allergic antibody responses of guinea pigs to nonproteolytic detergent enzymes in a mixture: implications for occupational exposure.

A guinea pig intratracheal test was developed to assess the respiratory allergenicity of enzymes used in the detergent industry. Information gained from this test was used in a process for setting operational exposure guidelines to protect worker health. Mixtures of enzyme proteins were given to guinea pigs once per week for 10 weeks to determine whether there were interactions among enzymes that affected the induction of antibody responses to each enzyme in the mixture. Passive cutaneous anaphylaxis antibody titers against each enzyme were measured in sera. Mixtures of two or three enzymes always consisted of a protease (Alcalase, Savinase; Novo Industri A/S) with an alpha-amylase (Termamyl; Novo Industri A/S), a lipase (Lipolase; Novo Industri A/S), or both. Control animals were exposed to single enzymes. The antibody titers to Termamyl and Lipolase were significantly greater in animals dosed with the protease-containing mixtures as compared with control animals dosed with a single enzyme. Antibody titers to the protease were unchanged in the presence of additional enzymes in the mixture. Complete inactivation of protease activity abrogated the enhanced antibody response to Lipolase. Inhalation exposure of guinea pigs to a mixture of Alcalase and Lipolase also resulted in higher antibody titers to Lipolase as compared with animals exposed by inhalation to Lipolase alone, showing that the enhanced response was not due to intratracheal delivery of antigen to the respiratory tract. These results show that proteolytic enzymes in a mixture enhance antibody responses to other enzymes. This should be considered when defining exposure guidelines for protease-containing enzyme mixtures.

Administration, Inhalation↗
PubMed1993

Respiratory and immunological responses of guinea pigs to enzyme-containing detergents: a comparison of intratracheal and inhalation modes of exposure.

Guinea pigs were exposed once a week for 10 weeks by intratracheal exposure to solutions of 3, 1, 0.3, or 0.1 micrograms of the enzyme protein, Subtilisn Carlsberg (Alcalase), in 250 micrograms of a detergent base. Other groups of guinea pigs were exposed by inhalation (6 hr per day, 4 days a week) to 1 mg/m3 of the aerosolized detergent base containing either 3.5, 1.1, 0.3, or 0.1% Alcalase protein. Evaluations of gross respiratory responses immediately following each intratracheal exposure revealed a significant dose response in respiratory symptoms measurable after the fourth exposure and continuing throughout the study. In the inhalation experiment, during Weeks 4 through 10, animals were observed to have respiratory symptoms which were dependent upon both the dose of enzyme and on total exposure to the enzyme/detergent atmosphere. For both intratracheal and inhalation routes of exposure, the initial appearance of respiratory symptoms coincided with the first appearance of measurable serum allergic antibodies specific to Alcalase. The allergic antibody levels increased with time and dosage by both routes of exposure, and the antibody titers generated by the intratracheal administration of antigen were comparable to those generated by the inhalation route of exposure. These results indicate that the intratracheal technique is appropriate for the evaluation of the respiratory allergic response to a protein.

Administration, Inhalation↗
PubMed1992

Antigenic and allergenic analysis of psyllium seed components.

The outer portions (husk) of psyllium seeds are a concentrated source of natural fiber used in some bulk-fiber laxatives and cereals. They are known to elicit respiratory allergic reactions after inhalation or ingestion among sensitized individuals. Antigenic and allergenic characterization of three psyllium-seed fractions (husk, endosperm, and embryo) was conducted with crossed immunoelectrophoresis (CIE), crossed radioimmunoelectrophoresis, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the source of psyllium allergenicity. Homologous CIE demonstrated psyllium endosperm and embryo extracts contained seven and four antigens, respectively. Husk extracts were too gelatinous to react by CIE. However, heterologous CIE profiles of endosperm or embryo extracts, reacted with antihusk antibodies, resulted in antigen-antibody precipitin peaks that matched the heavy staining precipitin lines of homologous reactions for endosperm and embryo, respectively. These results indicated that commercial-grade husk, endosperm, and embryo contained similar antigens. Extracts of all three seed components contained antigens that bound IgE antibodies in the sera of 11 psyllium RAST-positive individuals, as determined by crossed radioimmunoelectrophoresis. The few prominent husk protein/peptide bands resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were common in either embryo or endosperm. Immunoblots revealed common IgE reactive bands in all three seed fractions. Microscopic examination of the powdered commercial-grade psyllium (95% pure) revealed it contained endosperm and embryo particles. These immunologic, biochemical, and microscopic findings suggest that other contaminating seed components are primarily responsible for the allergenicity of commercial-grade psyllium-husk powder rather than the husk itself.

Allergens↗
PubMed1990

A review of the Buehler guinea pig skin sensitization test and its use in a risk assessment process for human skin sensitization.

The Buehler test is a valuable procedure for screening the sensitization potential of chemicals prior to human exposure. Our experience of over 20 years has shown it to be effective in detecting strong, moderate, and most weak sensitizers. The topical exposure inherent in the Buehler test allows it to be utilized to investigate dose responses, cross reactivity between structurally related chemicals, and the sensitization potential of contaminants in raw material mixtures. For safety assessment purposes, Buehler test results provide an initial indication of the sensitization potential of the material in question under relevant, but exaggerated, exposure conditions. These results can be compared to results on benchmark chemicals to assess sensitization risk for subsequent human exposure. Optimizing the sensitivity of the Buehler test requires adherence to the published methodology and proper interpretation of the challenge and rechallenge data obtained. Adjuvant-type test methods are generally considered to be more sensitive than topical methods. However, when done properly, topical test procedures such as the Buehler test or the open epicutaneous test can accurately detect most chemicals with any realistic potential for sensitizing humans by the topical route. Moreover, from a risk assessment perspective, these topical tests avoid the problems of overestimating the weak sensitization potential of many topically applied materials or underestimating the sensitization potential of very strong sensitizers; both are potential concerns with invasive adjuvant-type test methods. The Buehler test or other topical test methods are particularly valuable for comparative sensitization risk assessment since human sensitization data on benchmark materials are all derived from topical exposure. The risk assessment is developed by comparing the guinea pig data on the new material versus relevant benchmark chemicals or formulations and also by evaluating the existing human sensitization data on the benchmark material. These data are then utilized to predict human sensitization risk from topical exposure to the new material. Confirmation of human safety can be derived from human repeat insult patch testing (HRIPT) and other clinical tests such as the product use test and the diagnostic patch test. Utilized in this manner, the Buehler test is an integral component of an overall skin sensitization safety assessment program for a new chemical or product formulation.

Animals↗
PubMed1990

Antigenic and allergenic characterization of the enzymes alcalase and savinase by crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis.

Alcalase and savinase, produced by Bacillus species, are proteolytic enzymes that are used in laundry products and are known to cause respiratory allergy. Antigenic and allergenic characteristics of alcalase and savinase and their potential cross-reactivity were evaluated using crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis. Alcalase exhibited two distinct antigens; one electropositive and one electronegative. The electropositive antigen exhibited some retrograde anodic mobility when coupled with antiserum components. Savinase exhibited one electropositive and two electronegative antigens. The antigens of the two enzymes were clearly different from each other, the three savinase antigens exhibiting greater electrophoretic mobility than the two alcalase antigens. In crossed radioimmunoelectrophoresis studies, only the electropositive antigen of alcalase, its retrograde complex, and the electropositive antigen of savinase bound IgE from the sera of individuals who were skin test positive to one or both enzymes. No evidence of cross-reactivity was observed in heterologous and tandem crossed immunoelectrophoresis studies and heterologous microimmunodiffusion reactions.

Allergens↗
PubMed1985

A proposed plan for the detection and identification of potential sensitizers.

For toxicologists who are actively involved in safety testing and risk assessment, the ideal animal model should accurately predict the biologic response of humans after any contact with potentially hazardous materials. Unfortunately this goal is seldom, if ever, approached. Therefore, the toxicologist must design and execute experiments that will define to a higher degree of accuracy the inherent toxicity of the chemical and the biological response of the model. If the biologic response can be defined and understood and if the relevant information is available for comparable human responses, then the extrapolation to the human situation, although not always precise, can be made with a measure of assurance. Finally, and perhaps most importantly, it is essential that follow-up on human exposures be in sufficient detail so that the variations in biologic response can be further defined. In this way the precision and accuracy of the safety assessment can be checked.

Animals↗
PubMed1984

Association of high levels of serum antibody to staphylococcal toxic shock antigen with nasal carriage of toxic shock antigen-producing strains of Staphylococcus aureus.

Forty-four asymptomatic male subjects were examined for their nasal carriage of strains of Staphylococcus aureus capable of producing staphylococcal toxic shock antigen (TSA), an exotoxin implicated in the pathogenesis of toxic shock syndrome. In addition, the levels of antibody to TSA in sera from these subjects were determined by an enzyme-linked immunosorbent assay. S. aureus was isolated from the anterior nares of 23 subjects. Of those 23 isolates of S. aureus, 9 were found to produce TSA. All individuals carrying strains of S. aureus capable of producing TSA had high to moderate levels of antibody to TSA. In contrast, those individuals carrying strains not producing TSA had levels of antibody to TSA ranging from high to nondetectable. A second examination of nasal samples from 42 of these subjects revealed that 86% of those carrying S. aureus initially still carried S. aureus after a period of 3 months; all subjects found to carry TSA-producing strains initially and that were examined a second time yielded TSA-producing strains once again.

Adult↗
PubMed1975

Contact sensitization of guinea-pigs with unsaturated and halogenated sultones.

The sensitizing properties of unsaturated and halogenated sultones were examined in a guinea-pig model for contact hypersensitivity. The sensitization potential of 2-chloro-1,3-dodecanesultone was similar to that of 1-chloro-2,4-dinitrobenzene (DNCB). 2-bromo-1,3-dodecanesultone, 1-decene-1,3-sultone, 1-decene-1,3-sultone, 1-tetradecene-1,3-sultone and 1-hexadecene-1,3-sultone were stronger senistizers than DNCB. Ectensive cross-reactivity was observed among sultones of the same side-chain length, but differing from each other in being either unsaturated or halogenated. Extensive cross-reactivity was also noted among 4 unsaturated sultones of differing side-chain lengths. The inter-relationships among these sultones in regard to their immunogenic and tolerogenic properties are discussed.

Animals↗