Assessing the genotoxicity and carcinogenicity of 2-chloroethanol through structure activity relationships and in vitro testing approaches.

The detection of 2-chloroethanol in foods generally follows an assumption that the pesticide ethylene oxide has been used at some stage in the supply chain. In this situation the Pesticide Residues in Food Regulation (EC) 396/2005 requires 2-chloroethanol to be assessed as if equivalent to ethylene oxide, which has been classified as a genotoxic carcinogen. This review investigated whether this is an appropriate risk assessment approach for 2-chloroethanol. This involved an assessment of existing genotoxicity and carcinogenicity data, application of Structure Activity Based Read Across for carcinogenicity assessment, biological reactivity in the ToxTracker assay and micronuclei formation in HepaRG cells. Although we identified there is an absence of a standard oral bioassay for 2-chloroethanol, carcinogenicity weight-of-evidence assessment along with data on relevant structural analogues do not show evidence for carcinogenicity for 2-chloroethanol. The absence of genotoxicity was demonstrated for 2-chloroethanol and suitable analogues. In contrast, ethylene oxide showed reactivity towards markers indicative of direct DNA damage which is consistent with what is known about its mode-of-action. These data facilitate the understanding of 2-chloroethanol and given that it is not a genotoxic carcinogen suggest it must be assessed relative to non-cancer endpoints and a health protective Reference Dose should be established on that basis.

Threshold of toxicological concern (TTC) for botanicals - Concentration data analysis of potentially genotoxic constituents to substantiate and extend the TTC approach to botanicals.

This paper evaluates use of the Threshold of Toxicological Concern (TTC) approach to assess safety of botanical preparations that may contain potentially genotoxic constituents, based on estimation of the fraction that may be genotoxic. A database of 107 chemical constituents of botanicals was compiled and their potential for genotoxicity evaluated from published data. Forty-three constituents met the criteria for potential genotoxicity. Concentration data on their occurrence in plants provided 2878 data points; the majority were in the low ppm level (range 0.00001-139,965 ppm, by dry weight). Weibull models of the quantitative distribution data were used to calculate 95th percentile values for chemical concentrations, analysing the dataset according to their presence in botanicals (i) as a single chemical, (ii) as two or more chemicals from the same chemical group, or (iii) as two or more chemicals from different chemical groups. The highest 95th percentile concentration value from these analyses was 1.8%. Using the TTC value of 0.15 µg/person per day for potentially genotoxic substances proposed in 2004, this value of 1.8% was used to derive an adjusted TTC value of 10 µg of plant material on a dry weight basis/person per day for assessment of potentially genotoxic substances in botanicals.

Safety evaluation of superabsorbent baby diapers.

Superabsorbent disposable baby diapers are sophisticated, well-engineered products that provide many benefits including convenience, comfort, exceptional leakage protection, improved hygiene and skin care benefits compared with cloth diapers. Safety assurance is an integral part of the diaper development process at Procter & Gamble, with the goal of ensuring safety for both caregivers and babies. A systematic, stepwise approach to safety assessment starts with a thorough evaluation of new design features and materials, using the principles of general risk assessment including, as appropriate, controlled trials to assess clinical endpoints or independent scientific review of safety data. The majority of the diaper materials are polymers that are safe and do not have inherent toxicity issues. Trace amounts of non-polymeric materials, such as colorants, are assessed based on their skin contact potential. New materials or design features are introduced in marketed products only if they have been shown to be safe under the conditions of recommended or foreseeable use. The product safety continues to be confirmed after launch by means of in-market monitoring. This article provides a broad overview of human safety exposure-based risk assessment used at Procter & Gamble for absorbent hygiene products.