Pulmonary hypersensitivity to hexyl isocyanate-ovalbumin aerosol in guinea pigs

Karol, Meryl H.; Hauth, Beth Ann; Alarie, Yves

doi:10.1016/0041-008x(79)90009-7

Cited by 25 publications

(3 citation statements)

References 10 publications

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“…preparation of a suitable test antigen. Previously, we reported that guinea pigs sensitized by repeated inhalation of hexyl isocyanate-ovalbumin conjugate responded with production of antibodies directed exclusively to the hexyl isocyanate (HMI) hapten (Karol et al. 1979a).…”

Section: Introductionmentioning

confidence: 99%

Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker

Karol

Hauth

1982

Toxicol Sci

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Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker. Karol, M.H. and Hauth, B.A. (1982). Fundam. Appl. ToxicoL 2:108-113. Hypersensitivity to hexamethylene diisocyanate (HDI) has been reported following occupational exposure. Diagnosis of sensitivity is usually made from clinical evaluation of symptomatology. An in vitro serologic assay for HDI sensitivity was developed by immunizing guinea pigs with HDI and with hexyl isocyanate (HMI). Animals injected intradermally with HMI produced hapten-specific antibodies whereas guinea pigs injected with HDI produced antibodies specific for larger determinants which included the HDI hapten. The larger determinants were assumed to be composed of portions of "self" molecules which reacted in vivo with HDI. Serum albumin appeared to be one such molecule. No cross reactions were noted between antibodies to HDI and another widely used industrial isocyanate, toluene diisocyanate (TDI). Antigens effective in detecting antibodies to HDI or HMI were tested for ability to detect reaginic antibodies in a worker with clinical "HDI" asthma. Using a radioimmunoassay (RAST), antibodies reacted with conjugates containing either HDI or HMI as haptens. In addition, the prevalence of HDI polyisocyanates (Desmodur N) in spray paints prompted its use as a hapten. Antibodies reacted with Desmodur N antigen conjugates in RAST. RAST inhibition further indicated that Desmodur N antigen reacted more readily with the patient's antibodies than did HDI or HMI antigens. These results suggest that the patient may have been exposed to HDI polyisocyanates in spray paint application. Use of Rast inhibition for diagnosis of sensitivity may indicate the precise sensitizing agent within a mixture.

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Section: Introductionmentioning

confidence: 99%

Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker

Karol

Hauth

1982

Toxicol Sci

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“…Symptoms at all concentrations disappear within 3 months after ceasing exposure [99]. Pulmonary hypersensitivity assessed by an increased respiratory rate was developed [38]. Acute respiratory symptoms occurred requiring medical treatment.…”

Section: Methy/isocyanatementioning

confidence: 99%

Isocyanates

Brochhagen¹

1991

The Handbook of Environmental Chemistry

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“…However, many different mefhods have been used in guinea-pig models of occupafional asthma in regard fo sensifizafion regimen, mode of challenge, and protocol for fhe moniforing of airway reactivity. In studies on reactive organic chemicals such as acid anhydrides and isocyanafes, challenges have been performed by intravenous injection (10), inhalation of hapfen (11,12), inhalafion of aerosol (13,14), or intrafracheal instillation (15,16). Airway reactivity has been monifored by fhe regisfrafion of respiratory rate and tidal volume (11,13,14), pulmonary inflafion pressure (17), lung resistance (16,18,19), or dynamic compliance (18).…”

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confidence: 99%

Anaphylactic bronchoconstriction in immunized guinea pigs provoked by inhalation and intravenous administration of hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride

Zhao¹,

Zhang²,

Welinder³

et al. 1997

Allergy

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We established a guinea-pig model of anaphylactic bronchoconstriction provoked in immunized animals by inhalation and intravenous administration of 4,4-methyltetrahydrophthalic anhydride (MTHPA) and hexahydrophthalic anhydride (HHPA). Guinea pigs were immunized intradermally with either MTHPA (n = 8) or HHPA (n = 8) suspended in olive oil. Control animals (n = 8) were injected with olive oil alone. After 4 weeks, the animals were challenged during mechanical ventilation by inhalation or intravenous administration of MTHPA or HHPA conjugated with guinea-pig serum albumin (GPSA). Airway flow, and airway and esophageal pressures were measured. Resistance (R) and static compliance (Cst) of the respiratory system (rs), lung (1), and chest wall were studied with the flow-interruption technique. After challenge with MTHPA-GPSA or HHPA-GPSA, R,rs and R,1 increased dramatically while Cst,rs and Cst,1 decreased, and severe arterial hypoxia developed. The reaction occurred at a well-defined dose of anhydride and lasted about 30 min. When the same dose was repeated after 30 min, the response was much attenuated. MTHPA and HHPA can induce asthma in guinea pigs. The dose-response curve at antigen challenge is steep. Once a threshold dose is reached, a severe reaction occurs. The reactivity is then exhausted. This model may be suitable for assessing occupational asthma caused by acid anhydrides and possibly by other low-molecular-weight chemicals.

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Pulmonary hypersensitivity to hexyl isocyanate-ovalbumin aerosol in guinea pigs

Cited by 25 publications

References 10 publications

Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker

Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker

Isocyanates

Anaphylactic bronchoconstriction in immunized guinea pigs provoked by inhalation and intravenous administration of hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride

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