Validation of innovative technologies and strategies for regulatory safety assessment methods: challenges and opportunities.

Advances in science and innovative technologies are providing new opportunities to develop test methods and strategies that may improve safety assessments and reduce animal use for safety testing. These include high throughput screening and other approaches that can rapidly measure or predict various molecular, genetic, and cellular perturbations caused by test substances. Integrated testing and decision strategies that consider multiple types of information and data are also being developed. Prior to their use for regulatory decision-making, new methods and strategies must undergo appropriate validation studies to determine the extent that their use can provide equivalent or improved protection compared to existing methods and to determine the extent that reproducible results can be obtained in different laboratories. Comprehensive and optimal validation study designs are expected to expedite the validation and regulatory acceptance of new test methods and strategies that will support improved safety assessments and reduced animal use for regulatory testing.

Risk assessment of oral exposure to diisononyl phthalate from children's products.

Dialkyl phthalates are plasticizers used in household products made from polyvinyl chloride (PVC). Diisononyl phthalate (DINP) is the principal phthalate in soft plastic toys. Because DINP is not tightly bound to PVC, it may be released when children mouth PVC products. The potential chronic health risks of phthalate exposure to infants have been under scrutiny by regulatory agencies in Europe, Canada, Japan, and the U.S. This report describes a risk assessment of DINP exposure from children's products, by the U.S. Consumer Product Safety Commission (CPSC) staff. This report includes the findings of a CPSC Chronic Hazard Advisory Panel (CHAP) which: (1) concluded that DINP is unlikely to present a human cancer hazard and (2) recommended an acceptable daily intake (ADI) level of 120 microg/kg-d, based on spongiosis hepatis in rats. The risk assessment incorporates new measurements of DINP migration rates from 24 toys and a new observational study of children's mouthing activities, with a detailed characterization of the objects mouthed. Probabilistic methods were used to estimate exposure. Mouthing behavior and, thus, exposure depend on the child's age. Approximately 42% of tested soft plastic toys contained DINP. Estimated DINP exposures for soft plastic toys were greatest among children 12-23 months old. The mean exposure for this age group was 0.08 (95% confidence interval 0.04-0.14) microg/kg-d, with a 99th percentile of 2.4 (1.3-3.2) microg/kg-d. The authors conclude that oral exposure to DINP from mouthing soft plastic toys is not likely to present a health hazard to children. The opinions expressed by the authors have not been reviewed or approved by, and do not necessarily reflect the views of, the U.S. Consumer Product Safety Commission. Because this material was prepared by the authors in their official capacity, it is in the public domain and may be freely copied or reprinted.