Verification of literature‐derived SARs for skin irritation and corrosion

Abstract

Structural features known to irritate and corrode skin and physical properties associated with skin absorption were used to evaluate the irritation and corrosion potential of chemicals. Chemicals that irritate and corrode skin include organic acids and bases, aldehydes, halogenated esters, and chemicals with reactive groups. The activity of the reactive group decreases when sterically hindered by adjacent substituents or when electrons of the reactive group interfere with electrons of adjacent substituents. The structural features presented are a good basis for the calculation of SAR prediction rules. Also quantitative and qualitative physical conditions are given to predict skin irritation and skin corrosion.

Use of structural alerts to develop rules for identifying chemical substances with skin irritation or skin corrosion potential

“…Hulzebos et al [20] gathered structural alerts from literature. These 2-D alerts were estimated and drawn according to the description of the authors when no 2-D description was given in their paper.…”

“…The (Q)SARs of Gerner et al [15,16] based on physicochemical property limits for identifying chemicals with no skin irritation and corrosion potential can be expanded by the use structural alerts to identify chemicals with skin irritation and corrosion potential [15,16,20]. The purpose of this paper is to describe the structural alerts for skin irritation and skin corrosion of Hulzebos et al [20], in an unambiguous way that can be used for manual and computerized systems.…”

“…The purpose of this paper is to describe the structural alerts for skin irritation and skin corrosion of Hulzebos et al [20], in an unambiguous way that can be used for manual and computerized systems. In the present paper the structural alerts were categorized as irritation or corrosion or a combination of corrosion/irritation alerts, depending on their mechanisms of skin irritation and corrosion [21].…”

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

“…The database has been used to develop specific structure-activity relationship (SAR) models for predicting skin and eye irritation/corrosion, which have been incorporated into a decision support system (DSS) (Gerner et al 2000a(Gerner et al , 2000bZinke et al 2000). Recently these and other data have been used to verify skin irritation and corrosion predictions (Hulzebos et al 2003 Step 1: Data collection. The regulation was initially concerned, in phases I and II of the data collection step, with the so-called high-production-volume (HPV) chemicals: substances that have been imported or produced in quantities exceeding 1,000 metric tons per year and produced or imported between 23 March 1990 and 23 March 1994.…”

“…The substructures in SuCCSES that were associated with membrane irritation were included in a recent publication (Hulzebos et al 2003). A forthcoming book chapter (Walker and Gray.…”