Safety Assessment in the 21 st Century

Transcription

1 Safety Assessment in the 21 st Century PCPC Legal & Regulatory Conference 6 May 2016 Donald L. Bjerke, PhD, DABT The Procter & Gamble Company

2 Outline Common ground Safety assessment basic principles Safety assessment in the 21 st century How do we come to conflict? Case study endocrine disruptors Tool kit how do we come back together?

3 Consumers Industry Litigators Consumer products that are consistently safe, effective and of high quality Regulators NGOs Media

4 Assessing Risk The National Academy of Sciences (NAS) four-step Risk Assessment paradigm*: Hazard Identification Dose-Response Assessment Exposure Risk Characterization * From the National Research Council s Risk Assessment in the Federal Government: Managing the Process, Similar paradigms are used by international groups, IPCS.

5 Risk of an Adverse Event Safety Assessment Basic Principles High None None Exposure High

6 U-shaped Dose Response Curve

7 Applicability Domain ToxCast Hazard Aggregate Exposure SEURAT Mixtures COSMOS Algorithms Special Populations Point of Departure Genomics Validation Metabolomics ADME Expert Systems Epidemiology Human Relevance Safety Assessment in the 21st Century 7 th Amendment to Cosmetics Directive animal testing ban Systems Biology Structure Activity Relationship (SAR) Big Data Molecular Initiating Event (MIE) Benchmark Dose Modeling Tox21 Neural Networks Nanomaterials Structural Similarity In Silico Structural Alerts Margin of Safety Organ on a Chip Threshold of Toxicological Concern (TTC) Endocrine Disruption High throughput screening (HTS) Proteomics Adverse Outcome Pathways (AOPs) Regulatory Acceptance Metabolism Bayesian Modeling Microarrays Extrapolation Apical Outcome Primary Cell Cultures Klimisch Score Uncertainty Pluripotent Stem Cells Immortalized Cell Lines Risk Data Mining Dermal Penetration Physicochemical Properties Quantitative Structure Activity Relationship (QSAR) Read Across Carcinogen/Mutagen/Reproductive Toxicant (CMR) Probabilistic Weight of Evidence In Vitro to In Vivo Extrapolation (IVIVE) Physiologically Based Pharmacokinetics (PBPK) Computational Toxicology

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9 How do we come to conflict?

10 Beware of chemicals!

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12 Case Study Endocrine Disruptors

13 Puberty and Parabens: New Study Cites Risk Adolescent girls using personal care products free-of phthalates, parabens, triclosan, and benzophenone-3 for 3 days can reduce exposure to possible endocrine disrupting chemicals. Data demonstrated a reduction in some compounds in urine, no change in others, and an increase in some compounds (authors speculate about contamination or substitution of parabens).

14 Balanced Response by PCPC Toxicologist Dr. Linda Loretz notes that the levels reported for these ingredients have not been shown to cause negative health effects, and the mere presence of a substance does not translate to harm. Consumers are often confused by scary sounding claims about chemical risks that may sound sciencebased, but do not reveal anything about actual risk levels. For example, the presence of trace levels of synthetic chemicals found in the human body does not mean there is any danger to health. The substances that were included in the study are quickly excreted from the body, which is why they show up in urine, they do not bioaccumulate.

15 Did the EHP authors do their homework?

16 Subject Matter Experts

17 What does FDA have to say?

18 Tool Kit Independent subject matter experts Bradford Hill criteria strength of the association consistency and reproducibility of the effect temporality (effect occurs after the cause) biological gradient (greater exposure, greater incidence/effect) plausibility (biological mechanism) coherence between epidemiology and laboratory findings experimental evidence analogy (effect of similar factors) Questions to ask What is to be gained What biases could be present Myth busters (snope.com), coincidence, other explanations Do your homework, be skeptical but open minded

19 Beware of the Consequences The studies conducted to determine the hazard associated with inadequately preserved eye area cosmetics revealed that microbial contamination of new mascaras was rare but that many became readily contaminated with the microorganisms found on the eyelids and fingers of consumers. If an inadequately preserved mascara becomes contaminated with Pseudomonas aeruginosa and the delicate cornea of the eye is scratched with the applicator, the eye may become infected. P. aeruginosa is an ubiquitous microorganism which may also occasionally be present on the skin. Corneal ulceration may lead to partial or total blindness in the injured eye. Several cases of corneal ulceration and blindness associated with Pseudomonas-contaminated mascaras have been identified. Eye area cosmetics contaminated with Staphylococcus epidermidis or other cocci may cause conjunctivitis or blepharitis.

20 Questions?