Toxicodendron radicans Exposure may be harmful to your health - - PowerPoint PPT Presentation

Warning !!! Danger This location is contaminated with

Toxicodendron radicans

Exposure may be harmful to your health

POISON IVY

l we each eat ~ 1200 lbs of food a year l children eat more fruits and vegetables l total food business is >$700 billion ($340

billion at home and $360B in food service)

l ~ 12,000 new product introductions yearly l Government and educators are encouraging

greater consumption of fruits and vegetables for improved health (Food Pyramid)

l Greater interest in fresh foods - less

processing

The Food Environment

FOOD SCARES

l MSG l artificial sweetners l Alar in apples l Cyanide in grapes

Food Safety Issues

Safety Issues

l microbial toxins and pathogens l pesticides l environmental contaminants l migration from packaging materials l intentional or unintentional additives l animal drugs (antibiotics) l biotechnology products l tampering

Shakespear ÒMuch ado about nothingÓ

• r the problem of finding the

presence of and assessing the risk of potential chemical and biological hazards present at infinitely

Federal Structure

l Congress

➨committees investigate issues ➨companies and organizations lobby for viewpoint ➨Congressional Record ➨passes bills ➨overides veto of President

Federal Structure ¥ President Ðvetoes or signs bill. Becomes an Act (Law or Statute) US Code Ðassigns carrying out law to Departments, Agencies and Commissions Ðthese agencies propose Federal regulations- more depth

History

l 1906 Pure Food and Drug Act l 1906 Meat Inspection Act l 1947 FIFRA 86 Stat 975; 7 USC Sec 136 l 1938 Food Drug and Cosmetic Act l 1954 - Miller Pesticide Amendment 68 Stat

511 required pre-market testing & tolerance setting (Sec 408 of FFDC Act)

l 1958 Food Additives Amendment premarket

testing of additives and and Delaney Clause (zero tolerance for carcinogens)

l 1967 - Wholesome Meat Act 21 USC 672; Pub

L 90-201 pre-emption of States rights

l 1996 Food Quality and Protection Act

President President HHS HHS USDA USDA Treasury Treasury FDA FDA FTC FTC EPA EPA

CPSC Customs BATF

FSIS

Regulatory Procedure

l must follow Administrative

Procedures Act

l 701 (a) notice and comment l 701(e) allowance for

administrative hearing ➨food additives ➨pesticide tolerances ➨food standards

61 FR 46716 61 FR 46716

FR Parts

l Summary l Background l Comments l Conclusions l Economic Impact l Paperwork Reduction l Environmental Impact l CFR Parts

Code of Federal Regulations final steps after FR

l 9 CFR Meat l 21 CFR Food l 40 CFR EPA l 61 CFR Federal Trade Commission

21 CFR 100.80 21 CFR 100.80

Steps to Overturn Regulation

l give info during notice and comment

period, FDA must respond

l ask for administrative hearing if

701(e) reg

l after promulgated go to CCA

➨arbitrary ➨capricious ➨ripe for adjudication

FDA Other Material

l InspectorÕs Operations manual l Regulatory Procedures Manual l Compliance Policy Guides Manual

(CPGM)

l none have exact legal definitions but

are processes and legal notices of policy

Courts

l only come into play when there is a

challengeto thre law based on the Constitution

l Three levels

➨District ➨Circuit Court of Appeals ➨Supreme Court

l job is to interpert the law when conflict exists l Supreme Court

➨grants certiorari ➨A political process

Government Sanctions under FD&C Act

l Seizure l Injunction l Criminal - no intent necessary

➨ US v Park - vicarious responsibility ➨US v Hata - objective impossiblity ➨US v Starr - sabotage

l warning letter l Recalls - not mandatory

l 402(a)(3) - a food is adulterated if it

consists in whole or part of filthy, putrid or decomposed substances or is otherwise unfit for food

Food Drug and Cosmetic Act

filth is common definition - animal hairs, feces insects and parts etc

Case Study

l US v 133 Cases Tomato Paste 22 F Supp

515 (1938) ➨Harbor City Canning ships tomatoes from California to Philadelphia ➨tomatoes processed in July 1935 had corn ear worms, plant did no pre- inspection ➨worms broken upon canning so could not see them , also no taste and not injurious to health

US v 133 Cases Tomato Paste 22 F Supp 515 (1938)

l Court ruling:

➨filth has common meaning ➨must have protection of aesthetic sensibilities

• f consumers

➨processed worms constitute filth even though undetectable to eye ➨would only allow if small enough to be de minimus ➨level was above what FDA used as regulatory action level which was unpublished ➨Courts asked FDA to publish

US v Lazere 56 F. Supp 30; 1944

l filthy bakery l kids playing on flour with cat l numerous flies l testimony that filth is nutritious and

therefor does not make food unfit

l witness ate processed mouse l Court said must protect aesthtic

sensibilities

Regulations

l Prior to 1971 FDA kept filth

levels secret - only came out in Court cases

l 1971 Freedom of Information

Act - published info & started regulatory process

l 51FR 22480 - final rule 6/19/86

• created new defect action

levels and put in CPGM

Regulations

l 21 CFR 110.110

➨ (a) recognition of problem of contamination chance, always will be present even under GMP ➨(b) level set is necessary and feasible to attain- subject to change publish availability in FR and put in CPGM ➨(c) no excuse to violate 402 (a)(4) ie donÕt keep filth at maximum ➨(d) mixing not allowed

Defect Action Levels

l milled grain CPGM # 7104.06

➨six 50 gram samples ➨average of 75 or more insect fragments / 50 grams except not for durum or red durum wheat flour ➨or 1 or more rodent hair per 50 grams

l consumer wheat flour

➨- one rodent pellet / 5 lb bag

Defect Action Levels

l based on found levels from early

legal actions that US won

l later Industry worked with FDA to

help determine levels

l US v General Foods - machinery

mold case - no level so canÕt adjudicate

l processed potato history

Poisonous or Deleterious Substances

l pathogens l environmental toxins l carcinogens l mutagens l teratogens

Food Drug and Cosmetic Act

l 402(a)(1) - a food is adulterated if

it contains any poisonous or deleterious substance which may render the food injurious to health ➨example : pathogens such as

• E. coli O157:H7

➨examples : lead, mercury, radionucleotides

Pathogen Problem

l estimated 40 to 80 million illnessses

a year

l estimated > 9000 deaths ~ 2% of all

deaths per year

l estimated hospital costs > $3 billion

to $23 billion

l estimated productivity loss $9 billion l chronic long term illnesses possible

Pathogens

l no regulations setting standards for

maximum amount

l based on this zero tolerance ie may

be injurious to health ie one

• rganism can lead to problem for

some one

l actual action level based on ability to

determine, eg 1 Listeria / 25 g

l ? should level be set higher

Food Drug and Cosmetic Act

l 402(a)(1) - however if not added,

the food is not adulterated if the quantity would not ordinarily render injurious to health ➨example -selenium ➨example - solanine

l US v Seabrook Int'l. Foods

501 F Supp 1086 (1980)

➨Court granted summary judgment to FDA for three shipments of shrimp containing Salmonellae ➨Court ruled that salmonellae are added substances due to human intervention so 1st clause applied Òmay renderÓ thus any amount injurious otherwise if not added then can set Òde minimusÓ based on not ordinarily injurious ➨ under may render injurious ruling government can set maximum amount which can be zero ➨less burden of proof for US - donÕt have to show injurious to health at that level, only that it may render injurious

Question ?

What level is tolerable, if any? What do we do about environmental contaminants?

FD&C Act Section 406 Tolerances for poisonous or deleterious substances in food

l UNSAFE UNDER 402(a) (1) UNLESS

➨required in production ➨cannot be avoided in GMP ➨Secretary shall promulgate regulations limiting level

REGULATIONS 21CFR 109 Tolerances For Unavoidable Contaminants in Food or Packaging

¥EPA first established acceptable levels for delisted pesticides and FDA would accept tolerance for processed food and publish in 21 CFR

¥ FDA began working on these for environmental compounds but only one promulgated PCBÕs (took 10 years) ¥ under 701(e) forced to do in hearing process ¥ Court case by case basis began to lead to confusion

REGULATIONS 21CFR 109 Tolerances For Unavoidable Contaminants in Food or Packaging

Natick Paperboard v Weinberger

525 F. 2nd 1103 1st CCA 1975 l paperboard with PCB contamination l FDA seized whole output on basis

> 10 ppm PCB which was tolerance

l PCBs can migrate from packaging l PCB s are an unsafe additive

therefore subject to 409 and 406

l but Court ruled only paper destined

for food use can be seized

Case Studies

l US v Anderson Seafood 447 F Supp 1151

(1978) 622 F 2d 157 (1978)

l US seized fish with >0.5 ppm mercury l charged under 402(a)(1) 1st clause l District Court ruled Hg not added so 1st

clause applies as set too low

l Don't have to show intervention of man ie Hg

is unintentionally added so 2nd clause does not apply

l appeal by US to Circuit rejected so FDA had

to raise to 1 ppm see 44 FR 3990 January 1979 (this creates a case by case problem)

Case Studies

l US v Boston Farm 590 F 2d 149 (1979) l corn seized in interstate (Georgia to Florida) l in excess of action level for aflatoxin l District Court ruled aflatoxin was ÒaddedÓ

substance (1st clause) but level set by FDA too low so tried to raise aflatoxin tolerance to 100 ppb

l on appeal to CCA ruled to be kept at 20 ppb - l Court said should defer to FDA for scientific

findings

l 1980 FDA allowed corn @ 100 ppb for use in

livestock and poultry feed

REGULATIONS 21CFR 109 Action Levels For Unavoidable Contaminants in Food or Packaging ¥ required in process or ¥ cannot be avoided in GMP ¥ for-seeable probability to reduce ¥ not a reg so only notice and no comment ¥ Compiled in CPGM ¥ Note: most set at level of detectability

FDA/EPA Deleted Pesticide Tolerances in 1986

l Bypasses 701(e) l Set as action levels l Allows greater flexibility l Allows FDA to overide when in

national interest

Example Action Levels CPGM 7112 et seq

l Aflatoxin 20 µg/Kg food

5 µg/Kg milk (children)

l DDT - 0.5 - 5 ppm l Dieldrin 0.03-0.3 ppm l Lead 0.5 - 7 µg/mL leached

Young v Community Nutrition Institute

476 US 974, 90 L.Ed. 2nd 959 1986

l CNI sought Court action to make FDA

issue tolerance for aflatoxin because

• f 1980 corn incident

l SC granted certiorari l SC said FDA had discretion to act

under the statute ÒshallÓ is discretion

l Court would not substitute its

judgement for that of FDA

Radioactive materials in food

l Protective Action Guidelines l in CPGM

21 CFR 179

l Radiation which is a process is

deemed by reg as a food additive

l promulgated for meat, pork, poultry,

spices, fresh produce and fruits

l level of radiation is limited l both gamma and electron l informed consent label

Needs

l poultry is contaminated l 9 billion chickens per year l 8 viable plants l need to build at least 600 l NIMBY

Horror story

l Cobalt 60 unit l table legs l Tijuanna

Food Safety Problem with Contaminants

l CanÕt test all foods (ethics and imports) l JIT Processing (speed and economy) l lack of on-line sensors l lack of rapid methods l takes time for outbreak to occur

➨eg Hill Farm Dairy ➨eg Jack in the Box

Analytical Paradigm Shift

l Biotechnology l Material

science

l informatics

SENSOR PARADIGMS

l Simplicity - plant environment l Sensitivity (eg 1 Listeria in 25 g is one ppt

• ne ppt is 1 sec in 31710 years)

l Selectivity - interference l Sampling - how often and how much l Ruggedness

Food Additives Ammendment 1958

l 402(a)(2) A food is adulterated if it contains any

added poisonous or deleterious substance except one that is either:

l Generally Recognized As Safe 201(s) l Food Additive (Sec 409) l Color Additive (Sec 706) l New Animal Drug (Sec 512) l Tolerance Setting (Sec 406) l Pesticide (Sec 408) l Note that added means intentional addition

Additive Definition 201(s)

l Ò any substance, the intended use

• f which may reasonably be

expected to result directly or indirectly in its becoming a component or otherwise affecting the characteristics of any food.Ó

Sec 409 Unsafe Food Additive

A food additive shall with respect to any particular use or intended use shall be deemed to be unsafe unless (1) it and itÕs use is exempted or (2) there is a regulation limiting its use If regulation exists then not adulterated under 402(a)(1)

Housewares

l potential transfer of lead or other chemicals from

glaze or paints

l US v Article of Pottery 370 F. Supp 371, 1974 -

lead in dishware subject to FD&C Act as unapproved additive

l April 5, 1974 Federal Register Proposal -no prior

language to exempt housewares, foodservice utensils or food dispensors so FDA moved to clarify responsibility

Housewares Exemption

l 41 FR 34342 July 26, 1976 l MOU with Consumer Product Safety

Commission

l CPSC sets standards for consumer

products which are not foods

l mechanical hazards are under CPSC l agreed that migration from food

contact surfaces is food additive

l aresols are food components

Ceramics

l Mexican and Chinese pottery block

listed

l ArbyÕs Xmas glasses 1983 l 59 FR 1638 1/12/94 - Òrequirement

for label ÒNot for food use - May poison foodÓ or bore hole so not used to hold food

HOT ISSUE The Delaney Clause

Sec 409 (c)(3) Delaney Clause

No regulation shall issue if a fair evaluation before the Secretary (FDA) (a) fails to establish that the proposed use shall be safe Provided that no additive shall be deemed safe it it is found to induce cancer when ingested by man

• r animal or if it is found after tests which are

appropriate for their evaluation of the safety of food additives to induce cancer in man or animals

Cancer Consequences

l ~ 1.2 million new cases per year l 10 million with cancer in population l ~500,000 deaths per year from cancer l Direct Treatment Cost > $30 billion l Direct Productivity Loss $15 billion l Projected productivity loss due to premature

mortality $50 billion

l Total research ten times more for cancer than

for microbial food poisoning (~9,000 deaths per year)

Natural Carcinogens

l Mushroom Example Agaratine- DNA

breaker at 1.2 mg/70 Kg person

l present in mushrooms l safe dose < 4 g mushroom per day

• r 1 meal every 100 days

l Foods are GRAS so exempt

Dietary Risks potential cases per 106 population

l Saccharin l aflatoxin

~ 6

l phatalates

< 1

l DDT and other pesticides <0.6 l Total Known (?)

~200 of 5000

Cancer Causes

l smoking l air polution l water polution l diet ??? estimate 30% l genetics l rays from space

RISK ASSESSMENT

l actual occurrence l for a new substance assume allowed risk is

minimal @ 1 cancer death per one million population per life time ~ 260 potential incidents per year

l ~ 5000 new cases per million population per

year so if less than 1/million added risk is ~0.025 % of natural background

Saccharin

l Found to induce cancer in Canadian

mouse study when fed @ 5% in diet

l Congressional Action ÒSaccharin

Study and Labeling ActÓ 1980 PL 97- 273

l Package Warning Label Ò Use of this

product may be hazardous to your

• health. This product contains

saccharin which has been determined to cause cancer in laboratory animalsÓ

l Informed Consent l renewed every two years until

forgotten

C NH SO2 O

Interim Use Status

l 21 CFR 180.1 l created in 3/15/77 l based on potential safety issues that

may come up

l reasonable certainty that at present

level there is reasonable certainty of no harm to public health

l progress reports required on status

every 6 months

Interim Use Status

l BVO added in 2/84

➨toxic

l Mannitol added in 2/84

➨may cause diarrhea

l saccharin added in 2/84

➨carcinogen

62 FR 3791 1/27/97

Nitrite in cured meat

l nitrite used for centuries to cure

meat

l gives longer shelf life and pink color l USDA allowed for use in meat l in 20Õs discover that it also prevents

botulinum outgrowth so benefit

l in 60Õs find that cooking forms

nitsoamines - a carcinogen

Prior Sanction

l consumer groups seek to ban nitrite

but has no status

l FDA creates 21 CFR 181 for prior

sanctioned ingredients

l USDA produces letter to show gave

approval for use prior to 1958

l nitrite added to prior sanction list on

Jan 14, 1983

l USDA requires lowering of nitrite use

level

Packaging Materials

packaging materials are additives packaging materials are additives since contact food since contact food

Packaging

l 21 CFR 170.3(e) - food additive definition l any substance the intended use of which

results or may reasonably be expected to result directly or indirectly in their becoming a component of food or otherwise affecting the characteristics of foods. A material used in packaging is subject if it migrates

• therwise it is not a food additive.

Substances used in preparation of an ingredient may be a food additive.

l requires prior approval l regulated under 21 CFR 174 through 178

US v Monsanto 613 F. 2d 947 (D.C. Cir. 1979)

l deals with acrylonitrile co-polymer l residual monomer is a carcinogen present at 3.3

ppm

l approval was for polymer l brought conflict of law with science l potential vs actual diffusion l actual was at threshold of detection l FDA went to Court to ban acrylonitrile monomers l Court said FDA has discretion to determine as an

additive or not

Interim use status

l 21 CFR 180.22 March 1982 l added acrylonitrile co-polymers

Threshold of Regulation 60 FR 36582

l first proposed in Oct 1993 l Finalized 1995 l establishes max migration from food contact

surfaces

l level set at trivial amount of 0.5 ppb based

• n Òde minimus curat luxÓ called Òthreshold
• f regulationÓ

l migrant still considered food additive thus

DeLaney applies so can disapprove

l even though food additive no need for

regulation if below 0.5 ppb

recycled plastics

l 21 CFR 174.5(a)(2) ÒAny substance

used as a component of articles that contact food shall be of a purity suitable for its intended useÓ

l reused materials eg milk bottles l physical reprocessing l chemical treatment to separate

Pesticides

Pesticides Regulation

l EPA - evaluate the potential risk of an economic

poison before approval

l USDA - help farmers stay in business and supply

needed foods to the populace by using all possible methods

l FDA -determine if a pesticide is present in or on

foods and that its level of risk is as small as possible for all population subsets

EPA Role for Pesticides

l Evaluation of pesticides under FIFRA l all require registration 40 CFR 167 l defined as economic poisons l only covers Òraw agricultural commoditiesÓ

(RAC), not processed commodities (ie no Delaney like clause)

l re-evaluated every five years l Sec 408 of FFD&C Act applies for presence on

RAC

Pesticide Law

l Sec 402(a)(2)(B) food is adulterated

if it is a raw agricultural commodity and it bears or contains a pesticide chemical which is unsafe within the meaning of Sec 408

Sec 408 Tolerances for Pesticides in or on Raw Agricultural Commodities

l Raw Agricultural Commodity (RAC)

definition in Sec 201(r)

l is any food in its raw or natural

state including all fruits that are washed, colored or otherwise treated unpeeled

FFDC Act on Pesticides

l Sec 408(a) Any poisonous or deleterious

pesticide chemical which is not generally recognized as safe when added to a raw agricultural commodity shall be deemed to be unsafe with respect to 402(a)(2) unless either:

l (1) a tolerance has been established in or on the

raw agricultural commodity by the Administration

l when in force not subject to 402(a)(1)

Legal Control of Pesticides

l FD&C Sec 408(b) the Secretary (EPA) shall

establish a tolerance as safe on RAC to the extent to

l (1) necessitate the production of an

adequate, wholesome and economical food supply

l EPA publishes the limit (exemption) in

conformance with APA rules FDA must accept this tolerance as the legal limit on raw foods irrespective of the risk factor -

Imported Produce

l Circle of Poison - illegal to use

pesticides in US come back to us in imports

l History of soil use and illegal (non-

ethical) operations

l problem at processor level also

Pesticide Legislation

l Sec 402(a)(c) tolerance on Raw

Agricultural Commodity (RAC) also applies to processed form

• f commodity when ready to eat

l once set on RAC, pesticide

becomes a regulated food additive subject to 402(a)(c). True up until 1996

Pesticide Regulation

l However ÒProvided that where a pesticide

chemical has been used in or on a raw agricultural commodity in conformity with an exemption or tolerance under Sec 408 and such RAC has been subjected to processing such as dehydration .... notwithstanding the provisions of 406 and 409, such pesticide chemical remaining in or on such processed food shall not be deemed to be unsafe if such residue has been removed to the extent possible under GMP and the concentration in the processed food when ready to eat is ² the tolerance for the RAC

Pesticide Regulation

l Thus creates a problem if food is

concentrated (eg apple or orange juice and level goes up)

l In addition most regulators believed

that Sec 408 exempted pesticides in processed food from Delaney requirement even when in fact pesticide was a known carcinogen

Les v Reily

968 F.2d 985 (9th Cir.1992) 113 SCt 1361 (1993) cert denied l EPA refused to revoke food additive regulations

permitting use of four carcinogenic pesticides

• n grounds presented only deminimus risk

l Delaney Clause disallows any carcinogenic food

additive -

l Pesticides in processed foods are additives l Congressional Record very specific - EPA cannot

digress from original meaning

l Thus EPA has no discretion for non conformance

to Delaney for processed foods regardless of risk

NFPA 1992 Response

l Have EPA resolve that FD&D Act

does not apply to pesticides

l or if meets ready to eat on RAC have

it exempted when processed

l FDA Total Diet Survey 1985-1991 data l Study of eight foods used by infants and

children

l 0f 10,000 supermarket samples 50 were

violative ie non-allowed pesticides tested unwashed

l no sample over action level or tolerance set

by EPA

Actual Exposure JAOAC 76:492-508; 1993

6/28/93 EW Group Report

l millions of children receive 35% of

lifetime dose of carcinogenic pesticides by age 5

6/29/93 NAS Report

l US Government should remove or reduce use

• f and amount of pesticides deemed

hazardous

l create incentives for safe pesticides l will endorse Òintegrated pest managementÓ l coordinate regulations and practices of EPA,

USDA and FDA

l testing should be done on young animals,

eliminate the economic benefit process

California v Browner

• Feb. 2, 1995 9th DC CA

l FDA and EPA forced to begin

deletion process

l Feb. 25 EPA announces 9

revocations

l 31 substances not in processed

foods

l agreed to 81 revocations by April

1997

1996 Food Quality Protection Act

l Deleted defining pesticide on a processed food

as a food additive

l Changed Sec 408 of FD&D Act l if EPA sets tolerance cannot be deemed unsafe

under 402(a)(2)(B) which refers to food additives under Sec 409

l by default eliminates Delaney application as no

longer a food additive

What is the future?

definitions definitions threshold threshold carcinogens carcinogens law law regulations regulations public policy public policy