IFT Luncheon Talk on Prop 65

1. California Proposition 65 –
Current and Emerging Issues
James R. Coughlin, Ph.D. CFS
President, Coughlin & Associates:
Food/Nutritional/Chemical Toxicology & Safety
Aliso Viejo, California USA
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
Institute of Food Technologists
Joint Luncheon
Chicago
July 16, 2018

2. Presentation Outline
 Focus on IARC and U.S. NTP listings of chemicals
(Authoritative Bodies and Labor Code)
 Controversies over recent IARC classifications strongly impact
Prop 65 listings…
o Glyphosate
o Processed Meats / Nitrite
o A Pleasant Surprise…Coffee Gets help…finally!
 Maillard Browning Reaction carcinogens (acrylamide, 4-MEI,
furfuryl alcohol and beyond)…meet Prop 65!
 New Warnings Regulation
 IARC’s “Future Priorities” for evaluation will impact Prop 65
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3. “Proposition 65”
A California Law Passed by the Voters
“Safe Drinking Water and Toxic Enforcement
Act of 1986”
- “Right-to-Know” Warnings
- Prohibition of Discharge
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5. IARC vs. “Agriculture and Foods” (2015-2016)
 March 2015 – Glyphosate (“Roundup” herbicide for GMOs)
 Group 2A “Probable Human Carcinogen”
 “Sufficient evidence” in animals, “Limited” epi evidence (non-
Hodgkin lymphoma) + Mechanisms (genotoxicity & oxidative stress)
 June 2015 – 2,4-Dichlorophenoxyacetic acid (2,4-D) (herbicide):
 Group 2B “Possibly Carcinogenic” but no “sufficient evidence”
 First agency to ever call animal studies even “limited evidence”;
“oxidative stress” mechanism worsened it from Group 3 “not
classifiable”
 October 2015 – Red and Processed Meat
 May 2016 – Coffee, Group 3 “not classifiable as to its carcinogenicity”
 Improved from Group 2B “possible” (bladder cancer/1991).
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6. IARC and Prop 65 Take on Glyphosate…
 OEHHA proposes listing by Labor Code mechanism (Sept. 2015)
 OEHHA eventually lists glyphosate after court battles (July 2017)
 Safe Harbor Level of 1100 micrograms/day adopted (July 1, 2018)
 Recent court decisions (2018) -
 Court allows listing to stand
 U.S. District Court judge upheld preliminary injunction prohibiting
California from enforcing the warning requirement until a final ruling
on the matter is issued by the court
 Judge ruled that the overwhelming majority of agencies examining
glyphosate have determined it is not a cancer risk, and that the weight
of evidence is that glyphosate is not known to cause cancer.
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7. 7

8. IARC: Red & Processed Meat (October 2015)
 22 scientists on WG; 8 global meat industry Observers were silenced!; huge
negative media storm! And NTP Report on Carcinogens subsequently proposed
red and processed meat for inclusion in Fall 2016
 RED MEAT: [No “Sufficient Evidence” found = No Prop 65 listing is expected]
 Group 2A, “Probable Human Carcinogen”
 “Limited Evidence” in humans, colorectal cancer only
 “Inadequate Evidence” in animals
 Mechanistic considerations worsened the classification; WG members
were not shown the 18 written submissions by our global meat industry
 PROCESSED MEAT: [Will be listed by Prop 65, since Monograph is published]
 Group 1, “Human Carcinogen”
 “Sufficient Evidence” in humans, colorectal cancer only;
Relative Risk =1.18; barely statistically significant; IARC did not review all
the epi studies
 “Inadequate Evidence” in animals
 Mechanistic considerations worsened the classification.
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9. What Happens When
Maillard Browning Reaction Carcinogens
MEET Prop 65???
Acrylamide [1990, 2002]
4-Methylimidazole [2011]
Furfuryl Alcohol [2016]
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10. Ammonia
Alkyl amines
Amino acids
Proteins
Phospholipids
Aldehydes
Ketones
Sugars
Carbohydrates
Lipids
Carbonyls
Esters
Amides (Acrylamide)
Heterocyclic Compounds
Amine
Carbonyl
Amino-Carbonyl
Interaction
(Amadori Products)
HEAT
HEAT
Furans Oxazoles
Pyrroles Imidazoles
Thiophenes Pyridines
Thiazoles Pyrazines
Melanoidins
(pigments)
Volatile Compounds
(aroma chemicals)
General Scheme of Maillard Browning Reaction

11. Concentration Range of Food Contaminants
< 500,000
ppb
< 1,000 ppb
< 100 ppb
< 1ppb
• Furfuryl Alcohol
• Acrylamide - 2002
• Mycotoxins, PAHs
• Nitrosamines, HCAs
• Pb, As, Cd, Hg
• Dioxins
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12. Acrylamide Litigation
 French Fries
 Potato chips
 Cereals
 Coffee
 Veggie chips
 Toasted bread
 Hash browns
 Olives
 Granola bars
 Prune juice

13. 4-Methylimidazole
Listed as a Carcinogen Jan. 2011 based on NTP
Bioassay; IARC Monograph April 2011
~
Cola / Caramel Formulations Modified at Great Cost
to Get Concentrations below the NSRL
~
Also in Coffee and Other Heated Food &
Beverage Products
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14. Furfuryl Alcohol
Listed as a Carcinogen Sept. 2016 based on U.S. EPA as
Authoritative Body; IARC Monograph June 2017
~
“Failure to Warn” 60-Day Notices: began Fall 2017
[pretzels, baked potato/sweet potato-based snacks,
potato bread]
~
NTP cancer bioassay (1999) found it very weakly
carcinogenic via inhalation only [but not in females]
~
Fully metabolized to harmless compounds
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15. IARC Evaluated COFFEE in May
2016, Called it Group 3
“not-classifiable”
~
But Coffee Deserved a Group 4 or
even the Non-existent “Group 5”
[REDUCES Cancer Risk!]
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16. The “Coffee / Cancer Paradox”
 IARC and other global health and regulatory authorities now agree that
coffee drinking is NOT causing any increased risk of human cancer
 In fact, a massive number of human studies show significant risk
reductions for numerous cancers in spite of the presence of many animal
carcinogens [IARC did conclude this for liver and endometrium]
 How can this be?
 Naturally occurring antioxidants (chlorogenic acids)
 Heat-formed antioxidants (melanoidin polymers – coffee’s COLOR)
 Chemicals that induce detoxification enzymes (including glutathione
transferase)
 I have termed this the “Coffee-Cancer Paradox” – and it results from doing
“Benefit-Risk” evaluation of the whole beverage using the “Holistic
Approach”
So, the Paradox here is – Coffee contains many animal
carcinogens at trace levels but actually reduces some cancer
risks without raising others.
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18. Los Angeles Superior Court Lawsuit,
brought by Council for Education and
Research on Toxics [R. Metzger]
March 28,2018 Decision by Judge Elihu
Berle (6-year court battle)
Coffee must post cancer warnings!
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21. Future HIGH Priorities for IARC Monographs
Lancet Oncology 15: 683-684 (June 2014)
 Acrylamide, furan and 5-(hydroxymethyl) furfural [5-HMF]
 Aspartame and sucralose - Aspartame also a Prop 65 CIC “Medium/High
Priority” (Nov 2016)
 Beta-carotene – CARET chemoprevention trials’ data in high-risk groups
(cigarette smokers & asbestos exposed workers)
 Bisphenol A - in epoxy resins and plastics; ongoing debate about
carcinogenicity
 Iron (in food and as supplements) - intake exceeds recommended levels in
many women; epi studies of heme iron intake re: colon and other cancers
 Obesity and being overweight - increasing prevalence worldwide; many epi
studies of several cancer types available.
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22. Lessons to be Learned to Minimize the
Threats of Prop 65 Listings…
1. Know everything going on with all 5 Authoritative Bodies,
especially IARC & NTP…
try to prevent their worst classifications or decisions, or
minimize to less than “sufficient evidence”
2. Submit written comments on AB-based proposals to list;
Comment and testify to the CIC and DARTIC Committees to
prevent their listings outright, or at least to achieve “qualified”
less-damaging listings…
e.g., “Furfuryl Alcohol (by inhalation only)” would have been
a great victory for food and beverage products
3. BUT…THE VERY BEST OUTCOME IS TO PREVENT your
chemical or substance of interest from EVER being listed by
Prop 65 in the first place!!!
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23. Thank You!
~
Questions?
James R. Coughlin, PhD CFS
jrcoughlin@cox.net
949-916-6217