Introduction and Definition of Xenobiotics

• Xenobiotics = foreign chemicals not used by reference organism (human, animal, plant)
• Not essential for normal physiologic/biochemical function or homeostasis
• Not part of conventional array of chemicals synthesized from nutrients in normal metabolism
• Differs from xenobiology (search for extraterrestrial life)
• Can enter body purposefully (alcohol) or unknowingly (microbeads in lipstick)
• Essential amino acids like tryptophan don't qualify as xenobiotics despite being "foreign"

Scale and Prevalence

• Tens of millions of xenobiotics exist
• 52+ million organic/inorganic substances synthesized
• 39 million commercially available
• Average person exposed to 1-3 million different xenobiotic substances in lifetime
• 65% of chemicals in EU countries harmful to human health
• Field of toxicology struggles with proving harm conclusively

Classification Challenges

• EU has 17 groups of classifications for xenobiotics of most concern
• Massive overlap between categories makes classification difficult
• Classification important for research funding and scientific communication
• Renders system either too detailed (universe-wide book) or useless (everything in every category)
• Shows how new this field of understanding is

Ubiquity in Environment and Products

• Present in cosmetics, cooking pans, food packaging, shampoos
• In water we drink, air we breathe
• Passed through womb, breast milk, blood donations
• Found in Arctic and deep ocean
• Synthetic ones settled globally in most human bodies
• Microbeads banned from rinse-off cosmetics (2015 Microbead-Free Waters Act) but still allowed in lipstick/mascara

Body Processing Mechanisms

• Absorption: Goes into tissue, blood, back and forth
• Distribution: Shuttles between different body parts
• Biotransformation: Body breaks down into different parts
• Metabolism: Converted into new chemical compounds
• Elimination: Liver processes, then excreted via urine, feces, sweat, hair growth

Liver Processing and Metabolism

• Liver = primary processing center for xenobiotics
• Cytochrome 450 genes express enzymes dedicated to metabolizing xenobiotics
• Shows xenobiotics not new to human bodies evolutionarily
• Liver renders harmless, sends to kidneys/intestines for elimination
• Intestines may reabsorb, send back to liver for further processing
• Half-lives determine elimination timeframes (varies by individual health, age, weight)

Metabolite Formation and Risks

• Body can transform xenobiotics into entirely new compounds
• Sometimes creates more harmful metabolites than original substance
• Alcohol → acetaldehyde (carcinogen) → acetate (less toxic)
• Acetaldehyde causes genetic damage, liver scarring, cirrhosis
• THC example: absorbed in adipose fat, released when fat burned, can transform into new compounds

Ecosystem Parallels

• Ecosystems process xenobiotics similarly to human body
• Wetlands = "Earth's kidneys" - filter toxins from water
• Methods: trap in sediment, chemical/biological breakdown, sun exposure
• Algae/microorganisms can eat gasoline, break into less harmful parts
• Environmental half-lives differ from human body half-lives

Forever Chemicals and Persistent Pollutants

• Some xenobiotics called "forever chemicals" due to extremely long half-lives
• Example: Oxychlordane (pesticide metabolite) - 30-year half-life
• Environmental journalist Anna Turns had chlordane metabolite 30+ years after exposure as 1-year-old
• Passed from mother through womb, likely passed to her children
• Persistent Organic Pollutants (POPs) around since 1940s

PFAS (Per- and Polyfluoroalkyl Substances)

• 12,000+ forms in thousands of products
• Used in Scotchgard, Gore-Tex, Teflon, flame retardants
• Resistant to oil, heat, water due to strong carbon-fluorine bonds
• Washes out of products into wastewater systems
• No current method to remove from water supply
• Found in blood of 97% of Americans (CDC report)
• Linked to: endocrine disruption, low birth weight, immune system problems, multiple cancers
• Companies (DuPont, 3M) knew harmful effects since 1961
• EPA issued first guidelines 2016
• Potential lawsuits larger than tobacco settlements

Microplastics

• Defined as plastic particles <5mm
• Secondary: Broken down from larger plastics
• Primary: Manufactured and purposefully added to products
• Examples: Teflon coating on burger wrappers, cellophane wrap
• Released when washing synthetic clothing (Gore-Tex)
• Can evaporate from water into air, carried atmospherically
• Found in pristine Arctic areas via atmospheric transport
• Cellulose in shredded cheese prevents clumping (xenobiotic example)

Health Impacts and Cancer Risk

• Cancer often result of buildup from repeated exposure
• Xenobiotics that aren't easily cleared have more time to cause genetic damage
• Damaged DNA replication genes → uncontrolled cell growth → tumors
• Acute poisoning treatable with antidotes
• Chronic exposure more problematic
• Multi-year studies expensive, time-consuming
• Tens of millions of chemicals make comprehensive study daunting

Future Research Directions

• AI application to understand complex xenobiotic interactions
• Metabolomics: Measuring/quantifying every metabolic process in body
• Goal: Assign signatures to detect body's state at any time
• Currently mostly hypothetical, still relying on urine tests
• Post-mortem bone/fatty tissue analysis for xenobiotic presence

Safety Considerations

• Not all xenobiotics necessarily dangerous
• Dose makes the poison (Paracelsus principle)
• Soy isoflavones beneficial in small amounts, harmful in excess
• Natural doesn't mean safe, synthetic doesn't mean harmful
• Breast milk benefits vastly outweigh xenobiotic risks
• Impossible to 100% avoid but can minimize exposure
• Avoid products with known additives when possible