California’s Proposition 65: Recent Developments in Litigation, Regulation, and Compliance
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• Not all questions may be answered due to time constraints. If your question is not answered during the Q & A, email it to [email protected]. Please add to the subject line, “CRN Prop 65”. REND AL-MONDHIRY is Associate General Counsel at the Council for Responsible Nutrition (CRN) in Washington, DC. At CRN she provides legal counsel and advice to CRN’s staff and members in the areas of legislation, regulatory compliance and advocacy, and international policy development with respect to dietary supplements and nutrition issues. She also advises the association on a variety of general business matters, including contract drafting, negotiation and review, non-profit and association governance issues, and general corporate matters affecting CRN, CRN- International, and the CRN Foundation. Previously, Ms. Al-Mondhiry worked as state legislative counsel for Rend Al-Mondhiry the Consumer Healthcare Products Association Associate General Counsel (CHPA) where she provided testimony and comments CRN on legislative and regulatory proposals, drafted legislation and regulatory language and served as a policy expert in the area of food and drug law. Ms. Al- Mondhiry received her BA from The George Washington University and her JD from Pennsylvania State University, Dickinson School of Law. Agenda
New Clear and Reasonable Warning Regulations Anthony J. Cortez Shareholder, Greenberg Traurig LLP
Lead and the Beech-Nut Backlash Trenton H. Norris Senior Partner, Arnold and Porter LLP
The Threat of New Chemical Listings on the Horizon James R. Coughlin. Ph.D., CFS President & Founder, Coughlin and Associates
Practical Considerations for Dietary Supplement Manufacturers Paul R. Bolar Vice President, Regulatory Affairs, Pharmavite LLC Today’s Speaker Anthony is a regulatory attorney and business litigator with a focus on the representation of national consumer product companies and other businesses in compliance, commercial litigation, and government enforcement matters. Throughout California and nationally, Anthony advises and defends clients in legal, regulatory, and administrative proceedings involving numerous industries including food, drug, supplement, cosmetic, apparel, and industrial products, among others.
He is regularly involved in complex and high-dollar value litigation involving federal and state consumer protection and environmental laws, including CA’s Proposition 65, false adverting law, FTC regulations, and other labeling or Anthony J. Cortez marketing laws. He has handled matters involving the FTC, FDA, the CA Office of Environmental Health Hazard Shareholder, Assessment (OEHHA), the CA Department of Pesticide Greenberg Traurig, LLP Regulation (DPR), and the CA Department of Toxic Substances Control (DTSC). Today’s Speaker Trenton H. Norris litigates complex scientific disputes in the areas of consumer protection, product safety, and environmental law. His clients are consumer product manufacturers, distributors, and retailers facing challenges from plaintiffs’ lawyers, the FTC, state attorneys general, and local district attorneys. In his 23 years of practice, Mr. Norris has represented over a thousand companies, including over a hundred dietary supplement companies, in lawsuits and regulatory matters concerning state consumer protection and toxics laws, with a particular focus on California Proposition 65. Mr. Norris regularly advises trade associations in this area and is a registered lobbyist in California. Mr. Norris is listed in Chambers USA for both Environmental and Food & Beverages Regulatory and Litigation and in Best Trenton H. Norris Lawyers for Environmental Law. He received his law Senior Partner, degree magna cum laude from Harvard Law School, Arnold & Porter LLP where he was an editor of the Harvard Law Review. Today’s Speaker Dr. James R. Coughlin received his M.S. in Food Science and Technology, Ph.D. in Agricultural and Environmental Chemistry and postdoctoral training in Environmental Toxicology at the University of California, Davis. He is a Certified Food Scientist. He worked at Armour Foods, General Foods and Kraft General Foods for 12 years before undertaking independent consulting in 1991. He served as President of the Paris-based Association for Science and Information on Coffee and has been an ASIC Board member for the last decade. He was elected three times as Chair of the Institute of Food Technologists’ Toxicology and Safety Evaluation Division and has served for over a decade as IFT’s Codex Subject Expert on Food Contaminants. He specializes in safety evaluation and risk assessment of food additives/contaminants, James R. Coughlin, Ph.D., CFS California Proposition 65, health and regulatory issues for President & Founder, Coughlin & Associates: functional foods and supplements, and safety and Consultants in Food/Nutritional/Chemical regulatory issues surrounding coffee/caffeine, meats and Toxicology & Safety other major food products and ingredients. Today’s Speaker Paul Bolar is Vice President of Regulatory Affairs for Pharmavite LLC, a major manufacturer of dietary supplements and maker of Nature Made® supplements, based in Los Angeles. Since joining Pharmavite in 1974, Paul has held a number of positions, including oversight of quality control, quality assurance and regulatory affairs operations. In his current role, Paul is responsible for guiding the company in domestic and international regulatory matters.
Paul currently serves on the Board and the Executive Committee of the Council for Responsible Nutrition (CRN). He also served for many years as the chairman/co-chair of the CRN Regulatory Affairs Committee where he was actively involved in developing Paul R. Bolar and representing industry positions on dietary supplement VP, Regulatory Affairs Pharmavite LLC GMPs and other regulatory issues. Paul is a graduate of UCLA with a bachelor’s degree in biochemistry. CRN / Natural Products INSIDER Webinar California’s Proposition 65: Recent Developments in Litigation, Regulation and Compliance December 6, 2016
©2016 Greenberg Traurig, LLP. Attorneys at Law. All rights reserved. Greenberg Traurig is a Anthony J. Cortez Shareholder trademark and trade name of Greenberg Traurig, LLP and Greenberg Traurig, P.A. This presentation is intended for general GREENBERG TRAURIG, LLP | ATTORNEYS AT LAW | WWW.GTLAW.COM information purposes only and should not be construed as legal advice or legal opinions on ©2016 Greenberg Traurig, LLP. All rights reserved. any specific facts or circumstances. Why Are We Talking About CA’s Prop 65?
Greenberg Traurig, LLP | gtlaw.com 11 Increased Enforcement Activity Anticipated
> 2015 was a year of big cases, new trends – Less NOVs, but more $$$$: 1336 total NOVs (2015) vs. 1404 (2014) > All 2015 trends expected to continue/worsen in 2016 – Lead and Cadmium remain “low hanging fruit” > Food/Supplements still major targets > Possible 2016 new trends: Beta-myrcene, Pulegone, lead in non-supplement “foods,” BPA
Greenberg Traurig, LLP | gtlaw.com 12 The Litigation and Regulatory Environment
Food Cases Dominate 2016
> Coffee > Rice > Ginger Cookies/Baked Goods > Tea > Many notices for powders, bars, tablets, and herbal supplements
Greenberg Traurig, LLP | gtlaw.com 13 The Litigation and Regulatory Environment
Beech-Nut (Cal. App. 2014) decides several key defense issues:
Sample/lot analytical results can be averaged (for ‘bad apples’);
Non-daily consumption means exposure averaged over time;
NHANES database vindication (for proof of consumption rate); No “Beech-Nut Revolution” but…
ERC v. Aloe Vera Of America (Supplement): average consumption did not exceed 0.5ug/day (MADL) based on NHANES/labeling, however….
ERC v. Ardyss: admitted liability but 12k penalties + fees
Greenberg Traurig, LLP | gtlaw.com 14 The Litigation and Regulatory Environment
Environmental Research Center (ERC) continues to be the primary enforcer in the supplement space > Over $25 million in penalties and fees recovered > Significant uptick in the cost of settlement > Moving on to less obvious products
Others in food space: > As You Sow > Chanler > Center For Environmental Health
Greenberg Traurig, LLP | gtlaw.com 15 Regulatory Changes Coming Your Way
Greenberg Traurig, LLP | gtlaw.com 16 The Warning Requirement – That Sign You See Everywhere in California……….. is About to Change
WARNING: This product contains a chemical known to the State of California to cause cancer, or birth defects or other reproductive harm.
Safe-Harbor Product Warning
Greenberg Traurig, LLP | gtlaw.com 17 An Example of a New Food/Supplement Warning
WARNING: Consuming this product can expose you to lead, a chemical known to the State of California to cause cancer. For more information go to www.P65Warnings.ca.gov/food.
Greenberg Traurig, LLP | gtlaw.com 18 Under New Regs Chemical Must Be Identified
> Initially Only the 12 Target Chemicals (The Dirty Dozen)
acrylamide arsenic benzene cadmium chlorinated tris 1,4-dioxane formaldehyde lead phthalates mercury tobacco smoke toluene – No more generic safe harbor language – Chemical name must be included in the warning > Current Form Any Chemical Regardless if one of the 12
Greenberg Traurig, LLP | gtlaw.com 19 New Warning Regulations Key Changes
> Two- year phase in > Products manufactured prior to the effective date do not require new warnings > Clarifies that manufactures bear primary responsibility for warning – Manufacturer can add warning or provide to downstream retailers/distributors > Online warnings > No product inserts
Greenberg Traurig, LLP | gtlaw.com 20 The New Website Requirements
> Get Ready To Go Online! Regulations went into effect on 4/1/16 Businesses providing a warning must provide the Prop. 65 information, when reasonably available, upon the lead agency’s request, and within the timeframe specified in the request. Highlights: 1) The name and contact information for the person providing the information. 2) The name and contact information for the manufacturer of the product. 3) The name of the listed chemical for which a warning may be required. 4) The location of the chemical on or in the product. 5) The matrix in which the listed chemical is found in the product and the concentration of the listed chemical in the product matrix, if known. 6) The anticipated route, routes, or pathways of exposure to the listed chemical for which the warning is being provided. 7) Any other related information that the lead agency deems necessary.
Greenberg Traurig, LLP | gtlaw.com 21 Proposed “Reforms”: More Questions Than Answers (Continued) What is “supplemental information” that “contradicts” a warning?
“(d) A person may provide information to the exposed individual that is supplemental to the warning required by Section 25249.6 of the Act. In order to comply with this article, supplemental information may not contradict the warning. Supplemental information may not be substituted for the warning required by Section 25249.6 of the Act.”
Many questions: Does website information count? What if the information is truthful? What if a customer asks?
Greenberg Traurig, LLP | gtlaw.com 22 Proposed “Reforms”: More Questions Than Answers (Continued) Will old “out-of-court” settlements remain valid?
“(f) A person that is a party to a court-ordered settlement or final judgment establishing a method or content for a consumer product or environmental warning is deemed to be providing a “clear and reasonable” warning for that exposure for purposes of this article, if the warning fully complies with the order or judgment.”
Note, also covers only settlements involving “consumer products or environmental warnings.”
Greenberg Traurig, LLP | gtlaw.com 23 Greenberg Traurig LLP An International Firm of 2000 Attorneys & Government Law & Policy Professionals in 38 Cities
Greenberg Traurig, LLP | gtlaw.com 24 California’s Proposition 65: Recent Developments in Litigation, Regulation, and Compliance
Trenton H. Norris
Council for Responsible Nutrition/ INSIDER Webinar
December 6, 2016 arnoldporter.com Arnold & Porter LLP, All Rights Reserved. Agenda
. Lead and the Beech-Nut Backlash – The Beech-Nut Decision – Lawsuit Challenging the Lead Safe Harbor – The Agency’s “Pre-Regulatory” Proposals – Petition to List Lead Again – Possible Legislation
26 The Beech-Nut Decision
. Lawsuit filed by Environmental Law Foundation . Lead in baby foods, fruit juices, packaged fruit, and vegetables . Plaintiff claimed products exceed the lead safe harbor of 0.5 mcg/day . Defendants won on the safe harbor defense at trial . Defense victory upheld on appeal
27 The Beech-Nut Decision
. Three defenses raised — only one needed for defendants to win case: 1. Exposures to lead do not exceed 0.5 mcg/day safe harbor based on the “reasonably anticipated rate of intake or exposure by average users” *Defendants win on this defense only* 2. Lead is naturally occurring and exempt from Prop. 65 3. Lawsuit is preempted by a conflict with federal law . Very expert-heavy defenses
28 Beech-Nut: Safe Harbor Defense
Average amount of lead in a particular product X Amount of that type of product consumed by average 0.5 consumer when they eat it < mcg/day X Average consumption period of time over which a consumer eats the product type
29 Beech-Nut: Safe Harbor Defense
. Defendants averaged lead testing results . Defendants averaged exposures over a 14-day period using 14-day consumption surveys – The regulations support averaging over time if it is “scientifically appropriate” – Defendants argued no reproductive harm would result from the lead levels at issue if averaged over time – If the average user consumes a serving of a food product once every 14 days, that serving can effectively have up to 7 mcg of lead, not 0.5 mcg . Defendants used the geometric mean
30 Beech-Nut and averaging
. Defendants calculated “average” exposure levels using the geometric mean (not arithmetic mean) . The law does not define what is meant by “average” – Central tendency can be geometric mean, arithmetic mean, median . The geometric mean corrects for outliers that skew the distribution:
31 Beech-Nut Trial Court Ruling
. Court rules that lead levels do not exceed safe harbor . Judgment granted for defendants
BUT….
. Defendants failed to prove the amount of lead that is naturally occurring in origin – Trial court ruled that defendants were required to quantify the lead naturally occurring (i.e., 90 %, etc.) . Defendants failed to prove any conflict preemption
32 Beech-Nut Appeal
. California AG filed amicus brief seeking reversal – Granted oral argument . Justices focused on a narrow issue: Did trial court err in finding sufficient evidence proving the lead levels in the products? In other words, was the testing representative?
. Court of Appeal upheld ruling April 16, 2015 . The Beech-Nut Backlash begins….
33 Lawsuit Challenging Lead Safe Harbor
. Mateel Environmental Justice Foundation sued OEHHA in January 2015
. Mateel seeks to require OEHHA – to update lead safe harbor in light of science – to invalidate the lead safe harbor level of 0.5 mcg/day as illegally adopted in 1989 . California Chamber of Commerce and California Farm Bureau Federation joined litigation as intervenors
34 Safe Harbor Levels
. Warning thresholds described in the statute in narrative: – Listed Reproductive Toxicants: The exposure level that causes no observable reproductive effect, divided by 1,000 – Listed Carcinogens: Level causing no more than a 1 in 100,000 risk of cancer over a lifetime of exposure . Safe harbor levels for some chemicals published in regulations and quantified: – Presumptively valid – All expressed as micrograms of exposure per day
35 Safe Harbor Levels
. Safe harbor levels are based on a review of animal or human studies
– Studies must be of “sufficient quality” . OEHHA has published safe harbor levels only for a minority of the 800+ listed chemicals . If no safe harbor level is published, a business must prove the threshold level in litigation
36 Mateel Lawsuit Against OEHHA
. Mateel argues that the OSHA level on which the lead safe harbor level is based results in blood lead levels causing reproductive harm . OEHHA and Intervenors defend the safe harbor as based on the level that would have no observable effect . Trial court ruling (April 11, 2016): Mateel loses – Court defers to OEHHA’s scientific findings supporting decision to establish MADL of 0.5 mcg/day . Mateel appealed. Opposing briefs filed November 28, 2016. Oral argument anticipated in early to mid 2017.
37 The Regulatory Front
. Administrative petition filed in July 2015 by Center for Environmental Health to repeal or lower the safe harbor level for lead
. In response, OEHHA issues a “pre-regulatory” proposal on lead safe harbor level and averaging in anticipation of future rulemaking
38 OEHHA’s Pre-Regulatory Proposal on Safe Harbor Levels . Lead: OEHHA proposes a matrix of different lead safe harbors – Safe harbors range from 0.2 mcg/day to 8 mcg/day – Levels depends on different intervals of exposures (e.g., once every day, once every two days, once every five days, and so on....) . Other reproductive toxicants: Safe harbor levels for reproductive toxicants other than lead could not be averaged over time
39 OEHHA’s Pre-Regulatory Proposal on Naturally Occurring
. Specifies naturally occurring levels for arsenic in rice and for lead in certain foods and beverages:
Chemical Food Concentration (parts per billion)
Inorganic White rice grain 60 arsenic Brown rice grain 130
Lead Raw leafy vegetables 8.8 Raw non-leafy vegetables, 6.2 fruit, meat, seafood, eggs, and fresh milk
40 OEHHA’s Pre-Regulatory Proposal on Averaging
. Would say that “average” exposure means the arithmetic mean only (precluding geometric mean and median)
– “Long-standing” OEHHA position . Would not allow business to average test results across different lots of products (vs. from the same lot) – This lot-by-lot approach could require warnings for some lots but not others – Very hard to implement
41 OEHHA’s Pre-Regulatory Proposal
. Public workshops held in Oct. 2015 . Comments submitted by businesses, trade groups, environmental groups, and enforcers . Next steps? – OEHHA has not yet issued a formal proposal – Discussions between industry and activists
42 Petition to List Lead Again
. Mateel petitions OEHHA (Sept. 22, 2016) – Sought listing of lead as a female reproductive toxicant • NTP and US EPA: lead delays onset of puberty in females – Lead is already listed for • Male reproductive toxicity • Developmental toxicity • Cancer – Mateel seeking a fourth endpoint to lower safe harbor level . California Administrative Procedure Act does not apply to Proposition 65 listings
43 Petition to List Lead Again
. OEHHA denied petition (October 28, 2016)
– NTP is an “authoritative body,” but solely as to final reports of NTP-CERHR
– NTP Monograph on Health Effects of Low-Level Lead does not qualify
– US EPA is an “authoritative body”
– Delayed onset of human puberty is an effect on post-natal development, not an effect on female reproduction
– Post-natal development is not a Prop 65 endpoint
44 Possible Legislation
. Discussions underway between industry and activists . Consensus will be required – Proposition 65 can only be amended by 2/3rds vote of both the Assembly and Senate – Must “further the purposes” of Proposition 65 . Likely to include: – Naturally occurring concentration levels (ppb) for broad categories of foods – 0.5 mcg/day safe harbor level for lead on a single-day basis – Lack of action by OEHHA on averaging proposals
45 The Threat of New Chemical Listings on the Horizon
James R. Coughlin, Ph.D. CFS President, Coughlin & Associates: Food/Nutritional/Chemical Toxicology & Safety Aliso Viejo, California USA [email protected] www.linkedin.com/in/jamescoughlin
CRN / INSIDER Webinar Series December 6, 2016 Presentation Outline
What are the mechanisms for listing chemicals under Proposition 65? o Labor Code, State’s Qualified Experts, Authoritative Bodies, and State or Federal Agencies
NTP/IARC - historical coordination on herbals/supplements
Qualified listings (aloe vera, titanium dioxide, others)
Controversies over recent IARC classifications o Glyphosate, 2,4-D, red & processed meats o “Nitrite combined with amines or amides”
IARC Future Priorities (aspartame, sucralose, beta-carotene, iron in food and as dietary supplements, BPA)
U.S. House investigating funding of IARC Monographs 47 Four Mechanisms for Listing Chemicals
“State’s Qualified Experts” (Section 25305) -- Science Advisory Board (Carcinogen Identification Committee and Developmental and Reproductive Toxicant Identification Committee) can decide that a chemical has been “clearly shown…to cause cancer or reproductive toxicity.”
Authoritative Bodies (Section 25306) -- automatically listed if a body considered to be authoritative by the state’s qualified experts has formally identified it as causing cancer or reproductive toxicity.
State or Federal Agency (Section 25902) -- a chemical is listed if an agency has formally required it to be labeled or identified as causing cancer or reproductive toxicity.
California Labor Code -- certain animal and human carcinogens and reproductive toxicants identified by the International Agency for Research on Cancer (IARC) and the U.S. National Toxicology Program (NTP). 48 “State’s Qualified Experts”
Science Advisory Board
Carcinogen Identification Committee (CIC) - Currently 8 medical / toxicology experts
Developmental and Reproductive Toxicant (DART) Identification Committee - Currently 9 medical / toxicology experts
Meet once annually; review “Hazard Identification Documents” (HIDs); vote Yes/No on listing chemicals.
49 Five Prop 65 “Authoritative Bodies”
International Agency for Research on Cancer (IARC)
U.S. National Toxicology Program (NTP)
U.S. Environmental Protection Agency (EPA)
U.S. Food and Drug Administration (FDA)
U.S. National Institute of Occupational Safety and Health (NIOSH) 50 How does IARC classify agents/substances with respect to their cancer risk? IARC classifies compounds into 4 Groups based on the available scientific evidence for increasing cancer risk in animals and humans. The four classifications correspond to decreasing available evidence for cancer risk.
Group 1 Carcinogenic to humans
Group 2A Probably carcinogenic to humans
Group 2B Possibly carcinogenic to humans
Group 3 Not classifiable as to its carcinogenicity to humans
Group 4 Probably not carcinogenic to humans 51 “Labor Code” Listing Mechanism – Big Legal Battle
“Labor Code” (Sections 6382[b][1] and [d]) – Certain animal and human carcinogens and reproductive toxicants identified by IARC and NTP are required to be listed; Governor’s Initial List used the LC mechanism
OEHHA began using LC to list chemicals “ministerially” in 2004 [areca nut, betel without tobacco, aristolochic acids], after not using this mechanism for 17 years; this mechanism allows zero discussion of the science!
Sierra Club and other activist groups sued the state in Nov. 2007 over several causes of action, including a demand to list at least 92 LC substances, some in foods, supplements, consumer packaged goods
Appellate Court in SF backed the state in Dec 2012; but IARC chemicals with only “limited evidence” cannot be listed. 52 We Can Fight for “Qualified” Listings
If the chemical to be potentially listed has some modifying characteristics related to its carcinogenic or reproductive toxicity effects, we can press OEHHA, the CIC or the DART Committees to modify or “qualify” the listing
Best Examples: Aloe vera, non-decolorized whole leaf extract Alcoholic beverages, when associated with alcohol abuse Carbon black (airborne, unbound particles of respirable size) Chromium (hexavalent compounds) Retinol/retinyl esters, when in daily dosages in excess of 10,000 IU, or 3,000 retinol equivalents Silica, crystalline (airborne particles of respirable size) Sulfur dioxide (gas) Titanium dioxide (airborne, unbound particles of respirable size) 53 NTP Bioassays – Food & Supplement Ingredients Substance Levels of Evidence Already Listed Remarks (Clear, Some, (Likely to be?) (NTP Tech. Report) Equivocal, No) Chromium Picolinate Ginseng αβ-Thujone NOT SUFFICIENT NO All Final Technical Milk Thistle Extract Reports
Goldenseal Root Powder C – C – S – N YES TR 562 Dec. 2015 (2010) Ginkgo Biloba Extract S – S – C – C (Maybe) TR 578 IARC 2B (2016) (2013)
Aloe Vera Non-decolorized C – C – N – N YES TR 577 Whole Leaf Extract Dec. 2015 (2013)
Kava Kava Extract E – N – C – S (Maybe) TR 571 IARC 2B (2016) (2012)
Isoeugenol E – N – C – E (Maybe) TR 551 [Methyleugenol listed 2001] (2010)
Pulegone (mint oils) N – C – C – C YES TR 563 Apr. 2014 (2010)
β-Myrcene (citrus, other oils) C – E – C – E YES TR 557 Mar. 2015 (2010) 54 IARC’s Recent Classifications (Coffee, Glyphosate, 2,4-D, Red and Processed Meat)
55 IARC vs. “Agriculture and Foods” (2015-2016) - Monograph Meetings
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) Monsanto filed lawsuit to prevent California Prop 65 listing in Jan 2016
June 2015 – 2,4-Dichlorophenoxyacetic acid (2,4-D) (pesticide): Group 2B, “Possibly Carcinogenic” First agency in the world to call the animal studies even “Limited evidence”; but oxidative stress mechanism raised the call above the Group 3 “not classifiable” category
October 2015 – Red and Processed Meat: [see following slide]
Coffee – Monograph meeting May 24-31, 2016, Group 3 “not classifiable” 56 IARC: Red & Processed Meat Decisions (Oct. 2015)
22 invited scientists on Working Group; 8 global meat industry Observers (were silenced!); 8 days of deliberations; conclusions published two week later in Lancet Oncology
RED MEAT: [No Sufficient Evidence = No Calif. Prop 65 listing] Group 2A, “Probable Human Carcinogen” Limited Evidence in humans, colorectal cancer only Inadequate Evidence in animals Mechanistic considerations raised the classification
PROCESSED MEAT: [Will eventually be listed by Calif. Prop 65] Group 1, “Human Carcinogen” Sufficient Evidence in humans, colorectal cancer only [Relative Risk =1.18; barely statistically significant, translates to 18% increase in risk] Inadequate Evidence in animals Mechanistic considerations raised the classification CSPI petitioned USDA for cancer warning labels on December 1. 57 Sodium Nitrite - Carcinogen Listing Challenge
IARC Monograph No. 94 (July 2010) – 10-day meeting held June 2006; over 20 experts; I was Observer for AMIF “Ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans (Group 2A)” Limited evidence in humans for nitrite in food (stomach cancer) Limited evidence in animals for nitrite per se Mechanistic information raised it to Group 2A
American Meat Institute Foundation Expert Panel – completed 1.5-year effort to scientifically dispute IARC’s classification – Bryan, Alexander, Coughlin, Milkowski and Boffetta. 2012. “Ingested nitrate and nitrite and stomach cancer risk: An updated review.” Food Chem. Toxicol. 50: 3646-3665. Absolutely no response from IARC to date.
58 “Nitrite in Combination with Amines or Amides” – Carcinogen Listing Challenge [“Sufficient Evidence”]
Cited in IARC Monograph No. 94 (2010) on “Ingested Nitrite and Nitrate” classified as Group 2A “probably carcinogenic”
American Meat Institute and Grocery Manufacturers Association submitted comments objecting to this “Authoritative Bodies” listing in May 2014; would impact processed meats and all natural products
After consideration of our comments, OEHHA determined that the regulatory criteria for automatic listing had not been met
But the state notified us in May 2015 that they would ask the Carcinogen Identification Committee (CIC) to consider this for listing
The CIC evaluated this on November 15, 2016 and voted unanimously not to list, agreeing with our industry comments.
59 Future HIGH Priorities for IARC Monographs
Acrylamide, furan and 5-(hydroxymethyl) furfural - commonly found in cooked foods; cancer bioassay data are available
Aspartame and sucralose - widespread use and concern about their potential carcinogenicity
Beta-carotene - chemoprevention trials provide data on cancer incidence in high-risk groups (cigarette smokers and asbestos exposed workers) who were exposed to high doses
Bisphenol A - widely used in epoxy resins and plastics; ongoing cancer bioassays of perinatal exposure
Iron (in food and as supplements) - daily iron intake exceeds recommended levels in many women; epidemiological studies of haem iron intake and colon and other cancers are available
Obesity and being overweight - high and increasing prevalence; many epidemiological studies of several cancer types are available Lancet Oncology 15: 683-684 (June 2014) 60 IARC Controversies Raging in the Media, in Industry and within and amongst Public Health & Regulatory Bodies!
~ ~ ~
Mainly from Agriculture and Foods Classifications
61 62 63 64 65 66 Lessons to be Learned to Minimize the Threats…
1. Know everything going on with the 5 Authoritative Bodies early enough to try to prevent their final classifications or minimize their damage to less than “sufficient evidence”
2. Submit written scientific comments in response to AB-based proposals to list, and comment and testify to the CIC and DARTIC in order to prevent listings outright or to achieve “qualified” listings
3. THE BEST OUTCOME: Prevent your chemical of interest from EVER being listed by Prop 65 in the first place!
67 Naturally Occurring Constituents
. Recent listings of plant or plant-derived substances – Pulegone – Beta-myrcene – Goldenseal root powder – Aloe Vera, non-decolorized whole leaf extract
. The “naturally occurring” defense under Proposition 65 – 27 CCR section 25501(a): A chemical is “naturally occurring” if it is a natural constituent of a food – Natural (not synthetic) forms of these ingredients only
68 Naturally Occurring Constituents
. Pulegone
– “a natural constituent of various plants, including mint and other herbs, and of their essential oils”
. Beta-myrcene
– “Natural constituent of food plants, such as hop, bay, verbena, lemongrass, citrus, pomegranate, and carrot, and of their juices and essential oils.”
. Goldenseal Root Powder
– “a natural constituent of the goldenseal plant (Hydrastis Canadensis)”
. Aloe Vera, Whole Leaf Extract
– “consists of the liquid portion of the Aloe vera leaf and is a natural constituent of the Aloe barbadensis Millerplant” Naturally Occurring Constituents
. The Methyleugenol Letter (Jan. 2002)
. Addition to other foods or consumer products does not constitute “human activity” . No need to reduce to “lowest level currently feasible” or apply GAPs/GMPs
70 IARC Listing Mechanism
. Statute requires listing of all substances identified as Category 1, 2A, or 2B carcinogens by IARC with sufficient animal data . Allows automatic listings without consideration of science or even waiting for IARC monograph . Not used for many years; revived in mid-2000’s . Challenged in comments on areca nut and betel quid without tobacco (Nov. 2005) . Endorsed by Court of Appeal in Sierra Club v. OEHHA (2011) IARC Listing Mechanism
. Monsanto v. OEHHA (filed Jan. 2016, Fresno) – Challenges unaccountable rulemaking – Pleadings motions to be heard Dec. 2016 – Focused on glyphosate – But may affect multiple listings • Nickel compounds • Titanium dioxide • Benzophenone • Pulegone • Aloe vera • DEA/cocamide DEA • Mineral oils – May block future listings (e.g., processed meats) Proposition 65: Recent Developments in Litigation, Regulation & Compliance
Practical Considerations for Dietary Supplement Manufacturers
Paul R. Bolar CRN/Natural Products INSIDER Webinar December 6, 2016 ~800 chemicals listed under Prop 65 as Carcinogens and/or Reproductive Toxins
Examples of Prop 65 chemicals that may be of concern in dietary supplements
• Heavy metals • PCBs, Dioxins, Furans (marine products) • Lead • 4-Methylimidazole (caramel) • Cadmium • Various pesticides • Arsenic • Aloe Vera, non-decolorized whole leaf extract • Mercury • Goldenseal root powder “Safe harbors” can serve as an initial target for product specifications
Listed chemicals without safe harbors can be problematic Carcinogen Reproductive Toxin
0.5 mcg/day Lead 15 mcg/day* ( 0.2 mcg/day?)
Cadmium None* 4.1 mcg/day*
Inorganic Compounds Inorganic Oxides Arsenic 10 mcg/day* None
PCBs 0.09 mcg/day None
* Oral One size does not fit all
• Common industry raw material standards may not always satisfy Prop 65 requirements, e.g. > FCC > USP – Heavy Metals > GOED – PCBs
• Dietary Supplement manufacturers’ requirements for raw material specs may vary depending on formulation and total recommended daily intake Multiple dose Large tablets/capsules Powders products/Packs
Mineral tablets/ Calcium Botanicals Marine & Other Animal granulations sourced ingredients Consistent with GMP Reverse engineer finished principles, raw material product specifications to specifications are key to determine appropriate raw ensuring that finished material specs products meet Prop 65 requirements Qty./Dose Lead Spec Max. Lead/ Ingredient Unit ppm Dose Unit (g) (mcg/g) (mcg) Botanical Powder 0.5 1 0.5 Excipient A 0.2 3 0.6 Excipient B 0.1 5 0.5 Gelatin Shell 0.1 10 1.0 Total @ 1 Capsule/Day 0.9 2.8 Avg. Spec Needed To Meet 0.55 0.5 mcg Safe Harbor
Total @ 3 Capsules/Day 2.7 8.4 Avg. Spec Needed To Meet 0.185 0.5 mcg Safe Harbor Raw materials used in multiple finished products should have specifications set to meet worst case scenario.
Example: Dicalcium Phosphate (DCP) used in 3 different products:
DCP Used In: Required DCP Lead Spec Product A 3.0 ppm Product B 1.0 ppm Product C 0.5 ppm Reduce the recommended intake
Reformulate
Set separate specs for products shipped to California vs. rest of country
The “Naturally Occurring” exemption may be a defense, but is not a free pass • What is the original source of the contaminant? • Are cleaner alternatives available?
If all else fails … add the warning Know your ingredients Use safe harbors where possible to set specs Set raw material specs that support finished product needs Consider spec needs for all ingredients in the product Focus on high risk products and ingredients Consider maximum total daily intake Set raw material specs based on worst case finished product use Q & A Please send questions to our moderator using the Q & A feature on your screen Not all questions may be answered due to time constraints. If your question is not answered during the Q & A, email it to [email protected]. Please place “CRN Prop 65” in the subject line.
Trenton H. Norris Senior Partner James R. Coughlin, Ph.D., CFS Arnold & Porter LLP President & Founder 415-471-3303 Coughlin & Associates [email protected] 949-916-6217 [email protected]
Paul R. Bolar Anthony J. Cortez VP, Regulatory Affairs Shareholder Pharmavite LLC Greenberg Traurig LLP 808-221-6260 916-868-0679 [email protected] [email protected]
Rend Al-Mondhiry Associate General Counsel CRN 202-204-7672 [email protected] Thank you for attending today’s Webinar sponsored by:
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