Skin sensitization risk assessment: a comparative evaluation of 3 isothiazolinone biocides.

Many of the chemicals in common use possess, to some degree, a capacity to cause skin sensitization. Consequently, it is important to conduct a thorough and accurate risk assessment when it can be anticipated that such chemicals are likely to come into contact with human skin. Such risk assessments must consider the nature and extent of dermal exposure together with the sensitizing potency of the chemical. Whilst the exposure elements of the risk assessment process are often well understood, or can at least be reasonably predicted on the basis of the proposed usage of the chemical, the determination of skin sensitizing potency may be problematic. In this paper, we describe an approach to the determination of relative potency of 3 isothiazolinone biocides. Initially, the local lymph node assay (LLNA) provides an estimate of relative sensitizing potency. Where appropriate, this can be followed by confirmatory testing in the human repeat insult patch test (HRIPT). The data generated reveal that (chloro)methyl isothiazolinone (CMI) is a significantly stronger sensitizer than either methyl trimethylene isothiazolinone (MTI) or benzisothiazolinone (BIT). Furthermore, both the LLNA and the HRIPT data show consistently that BIT is a somewhat weaker skin sensitizer than MTI. As an important additional component of the safety evaluation, the ability of these sensitizing isothiazolinones to cross-react has been considered; the data indicate that the more weakly sensitizing isothiazolinones do not elicit allergic reactions in subjects sensitized to MCI. The implications for use of these biocides in various product types are discussed.

The value and limitations of protective gloves in medical health service: Part III.

The value of protective gloves in the health care environment is well known. However, these gloves are not perfect. Some are permeable to microorganisms and various chemicals, and/or result in side effects for health care professionals. Gloves that offer the greatest protection and least side effects are highly desirable. Limitations of glove use due to side effects, and glove selection and therapeutic alternatives are described in Part III of this three-part series.

The value and limitations of protective gloves in medical health service: part II.

The value of protective gloves in the health care environment is well known. However, these gloves are not perfect. Some are permeable to microorganisms and various chemicals, and/or result in side effects for health care professionals. Gloves that offer the greatest protection and least side effects are highly desirable. Protection against microorganisms and protection against chemicals used in health care are described in Part II of this three-part series.

The value and limitations of protective gloves in medical health service: Part I.

The value of protective gloves in the health care environment is well known. However, these gloves are not perfect. Some are permeable to microorganisms and various chemicals, and/or result in side effects for health care professionals. Gloves that offer the greatest protection and least side effects are highly desirable. Field of application rules and regulations, materials and manufacturing, and test methods of protective gloves are described in Part I of this three part series.

Structure-activity relationship as a tool in contact allergy risk assessment.

About 3000 substances are known to cause contact allergy (type IV allergy). The possibility of predicting the sensitizing capacity of a substance by examining its chemical structure is discussed on the basis of the authors' own experience and of literature data. Since other factors also influence the allergenic activity of a compound, indications based on chemical considerations must be confirmed experimentally in animals because no in vitro methods yet exist.

Measurement of skin-fold thickness in the guinea pig. Assessment of edema-inducing capacity of cutting fluids, acids, alkalis, formalin and dimethyl sulfoxide.

The rabbit has been used for decades for predictive testing of skin irritancy, but in recent years, the guinea pig has been suggested as an alternative, especially for assessment of one of the components of the irritant reaction: edema (fluid accumulation). A method based on skin-fold measurements with Harpenden calipers has been developed and modified. In previous papers, experience with sodium lauryl sulphate, nonanoic acid and industrial solvents was reported. The present results concern the use of cutting fluids, buffered and unbuffered acid and alkaline solutions, formalin and dimethyl sulfoxide. This inexpensive and comparatively unsophisticated method afforded clear dose-response relationships and good discriminating power. The only exception was the acid and alkaline solutions, where no changes in skin-fold thickness were observed despite their documented irritant potential. The appearance of erythema (visual scoring) and the increase in skin-fold thickness, and their relationship, are discussed with some illustrative examples. The method described is now well standardized and is suited for predictive testing of the edema-inducing capacity of chemicals and products.

Assessment of skin irritancy: measurement of skin fold thickness.

It is desirable to use more objective methods than visual scoring for the assessment of skin irritancy reactions. The edema, or fluid accumulation in the exposed skin sites, can be accurately measured by a caliper and this alternative method of assessment is evaluated from different aspects. Sodium lauryl sulfate (SLS) and non-anoic acid in different concentrations were applied daily to human and animal (rabbit and guinea pig) skin, and a dose-response relationship established. Higher concentrations of the irritants induced an earlier response. With 5% SLS as the test substance and the increase in skin fold thickness as the single parameter of skin irritancy, the guinea pig was found to be less reactive than rabbit and man. Measurement techniques, reproducibility and advantages and disadvantages with different animal models are discussed.

Assessment of skin irritancy in man by laser Doppler flowmetry.

It is desirable to use more objective methods than visual scoring for the assessment of skin irritancy reactions. In the present study the blood flow in skin sites exposed to sodium lauryl sulfate (SLS) was recorded by a laser Doppler flowmeter. The irritant was applied to the volar forearm of healthy volunteers in concentrations ranging from 0.001% to 5% under occlusion for 24 h. The test sites were scored visually and the blood flow was recorded at 3 different times: 26 h, 48 h and 72 h after the application of SLS. Approximately 950 recordings were performed and a clear relationship was observed between the applied doses of SLS, the recorded blood flow values and the corresponding scores. In a few cases a deviation from the general trend was observed, implying that the naked eye might be unreliable for the assessment of skin irritancy reactions.

Assessment of chromium allergy: features of patch test reactions at electron microscopic resolution.

The possible correlation of clinically recorded test reactions and morphological changes at electron microscopic resolution in human subjects allergic to chromate (CrVI) was investigated. The effect of simple occlusion and of vehicles, e.g. distilled water, an alkaline buffer, and petrolatum was also studied 72 hours after application. The results indicate that even simple occlusion causes reactive changes in living epidermal cells. These changes become conspicuous in occlusion with distilled water, more pronounced with petrolatum, and were destructive in the case of the alkaline buffer. Chromate solutions produced varying degress of morphological change but were less pronounced in a vehicle of distilled water, compared with the changes seen when the chromate was combined with the alkaline buffer. Destructive cellular changes were observed in the electron microscope even in sections from test ares where no macroscopical reactions were recorded. When the clinical evaluation of hypersensitivity was done 72 hours after the application of the patch test the morphological changes were too advanced to provide specific pathognomonic information.