RISK ASSESSMENT OF

FOOD CONTACT
MATERIALS
November 2017
Nicholas Jermstad, Senior Manager,
Food Contact Regulations, Intertek US Health,
Environmental, & Regulatory Services
AGENDA

01 Introduction and Definitions

02 How to find Relevant Data

03 Calculations

04 Infant Formula Restrictions

Risk Assessment of Food Contact Materials - November 2017

01
INTRODUCTION AND
DEFINITIONS
DESCRIBE THE TOXICITY AND
DEMONSTRATE THE SAFETY OF ALL CHEMICALS MIGRATING TO FOOD

food

( including low-level impurities and transformation products )

HOW CAN YOU ENSURE THAT THIS COMPLIES?

Risk Assessment of Food Contact Materials - November 2017

DIRECT AND INDIRECT FOOD ADDITIVES

Outer
layer film

Indirect food
additives
Added to the ink

Indirect Food additive

added to the barrier film

Indirect food additive

adhesive layers
Indirect Food
Additives Oxygen Barrier
Indirect food additive
added to food contact film

Direct Food Additives

added directly to the food
02
HOW TO FIND
RELEVANT DATA
RESEARCHING DATA FOR A COMPREHENSIVE ASSESSMENT
IARC SAR Models

Chem ID
Product Composition Carcinogens NTP
AIM (Analogs)

Mutagens TOXNET FDA ADI Table

OECD SIDS CPDB

General Toxicity
EPA HPV
eChemPortal
CAS No. EPA IRIS

FDA Databases & FOI

Structure

MITI
Chemical Name Government Clearances

EPA TSCA Files

Food Safety Issues

EFSA

Google

Risk Assessment of Food Contact Materials - November 2017

Decernis
READ-ACROSS, QSAR AND
THRESHOLD OF TOXICOLOGICAL
CONCERN (TTC)

• Where toxicological data are available

on substances with similar chemical
structure, read-across can be used
• QSAR approaches can also be useful
• Where little or no toxicological data are
available, the Threshold of Toxicological
Concern approach can be used.

Risk Assessment of Food Contact Materials - November 2017

STRUCTURAL ALERTS FOR MUTAGENICITY AND CARCINOGENICITY

Tennant and Ashby 1991

Risk Assessment of Food Contact Materials - November 2017

STRUCTURAL ALERTS

TOXTREE Model

Risk Assessment of Food Contact Materials - November 2017

03
CALCULATIONS
CALCULATION OF DIETARY CONCENTRATION (DC) AND THE ESTIMATED
DAILY INTAKE (EDI)

• Dietary concentration (DC) and Estimated Daily Intake (EDI) of a substance is calculated based on
results from migration studies (or 100% migration calculations) but taking into account:
• DC = Migration x Consumption Factor
• The term "Consumption Factor" (CF) describes the fraction of the daily diet expected to contact specific
packaging materials. The CF represents the ratio of the weight of all food contacting a specific packaging
material to the weight of all food packaged.

http://www.cfsan.fda.gov/~dms/opa2pmnc.html

Risk Assessment of Food Contact Materials - November 2017

EXAMPLE CONSUMPTION FACTOR (CF) TABLE

TABLE I - CONSUMPTION FACTORS (CF)

Package Category CF Package Category CF

Polymer 0.4

B. Polymer

Polyolefins 0.35 PVC 0.1

-LDPE 0.12 -rigid/semirigid 0.05

-LLDPE 0.06 -plasticized 0.05

-HDPE 0.13 PET(a) 0.16

-PP 0.04 Other Polyesters 0.05

Risk Assessment of Food Contact Materials - November 2017

CALCULATION OF DIETARY CONCENTRATION (DC) AND THE ESTIMATED
DAILY INTAKE (EDI)

DC = Migration x Consumption Factor

Estimated Daily Intake (EDI):
• EDI = DC x 3 kg food/person/day

http://www.cfsan.fda.gov/~dms/opa2pmnc.html

Risk Assessment of Food Contact Materials - November 2017

SAMPLE DC AND EDI CALCULATIONS

Example: A Colorant for use in All Polymers:

• The colorant migrates from LDPE polymer:
• Migration study data = 125ppb in food

• DC = CF x Migration
• CF (Colorants for All Polymers) = 0.05
• Dietary Concentration (DC) = 0.05 x 125 ppb
• Dietary Concentration (DC) = 6.25 ppb
• EDI = 6.25 ppb x 3kg/person/day = 18.75 ug/person/day Assuming 60 kg human = 0.313 ug/kg/day

http://www.cfsan.fda.gov/~dms/opa2pmnc.htm

Risk Assessment of Food Contact Materials - November 2017

ACCEPTABLE DAILY INTAKE (ADI)

The Acceptable Daily Intake (ADI) must be determined

NOAEL(animal - mg/kg/day)
ADI = Safety Factor

Safety Factors based on: Safety Factor Calculation:

• 90-day study (1) – 2000x • Inter species 10
• 90-day study (2) – 1000x • Intra species 10
• Repro/Development – 100 to 1000x • Subchronic to chronic 10
• 2-year study – 100x 10 x 10 x 10 = 1000

• ADI must be greater than the EDI (Estimated Daily Intake)

• Margin of Safety (MoS) = ADI ÷ EDI; If >1, the application is considered safe

Risk Assessment of Food Contact Materials - November 2017

SAMPLE DC AND EDI CALCULATIONS

Example: A Colorant for use in All Polymers:

EDI = 6.25 ppb x 3kg/person/day = 18.75 µg/person/day

Assuming 60 kg human = 0.313 µg/kg/day

NOAEL = 10 mg/kg/day (Reproductive Tox Study)

ADI = 10 mg/kg/day ÷ 1,000 = 0.01 mg/kg/day
MoS = ADI ÷ EDI
MoS = 10 µg/kg/day ÷ 0.313 µg/kg/day
MoS = 31.9

Safe for this Application

Risk Assessment of Food Contact Materials - November 2017

04
INFANT FORMULA
RESTRICTIONS
FCN – RESTRICTIONS IN INFANT FORMULA

Since 2010, FDA has added restrictions to FCN approvals:

“contact with all food types except infant formula”

This statement was added regardless of application

For approval for use in infant formula containers (e.g. lining of formula container, baby bottles, etc.), a
separate safety assessment and toxicity data must be completed

Risk Assessment of Food Contact Materials - November 2017

FDA ASSUMPTIONS FOR INFANTS

Infants 0-6 months General Population

Food Consumed (g/day) 900 3000

Body Weight (kg) 6.3 60
Food consumed relative to body wt (g/kg bw/day 143 50
Consumption Factor (CF) 1.0 (all food comes from formula) 0.0004-0.35

Risk Assessment of Food Contact Materials - November 2017

DIFFERENCES IN ESTIMATED DAILY INTAKE

Dietary Concentration (DC) = CF x Migration

Estimated Daily Intake (EDI) = DC x Food Consumed Per Day ÷ Body Weight
DC will be higher for infants because no CF
Food Consumed/Day = 3,000 g/day for General Population; 900 g/day for infants
Body Weight = 60 kg for General Population; 6.3 kg for Infants
EDI will be significantly different for same substance

Risk Assessment of Food Contact Materials - November 2017

TOXICOLOGY REQUIREMENTS: FCNS (EXPRESSED IN EDI)

Estimated Daily Intake (µg/kg bw/day) Recommended Toxicity Data

<0.025 No data needed

0.025 - 2.5 2 in vitro genotoxicity studies
Above
2.5 – 50 And in vivo genotoxicity study
And oral subchronic studies for 2 species
Above
>50
And more testing as recommended by FDA

Based on our experience, for infant formula, the top 2 tiers are the same
For the 3rd tier, FDA has asked for Developmental Toxicity data

Risk Assessment of Food Contact Materials - November 2017

EXAMPLE

• Additive X used in HDPE Beverage Container

• 2 negative in vitro genotoxicity studies; no other data
• This supports EDI of 0.025-2.5 µg/kg bw/day

• Migration:
• 10 ppb (10% EtOH for acidic and aqueous) and 200 ppb (95% EtOH for fatty and alcoholic)

• General Population:
• DC = 0.13 x [(0.67)(10 ppb) + (0.01)(10 ppb) + (0.01)(200 ppb) + (0.31)(200 ppb)] = 9.2 ppb
• EDI = (9.2 ppb x 3 kg food/day) ÷ 60 kg bw/person = 0.46 µg/kg bw/day
• This EDI can be supported in FCN with available data

Risk Assessment of Food Contact Materials - November 2017

EXAMPLE (CONT’D)

Infant Formula Container

• DC = 1.0 x 200 ppb (milk is a fatty food)
• DC = 200 ppb
• EDI = (200 ppb x 0.9 kg food/day) ÷ 6.3 kg bw/infant = 29 µg/kg bw/day
• This EDI cannot be supported with the available toxicity data

The same HPDE additive is acceptable for the general population, but not for infant application.

Risk Assessment of Food Contact Materials - November 2017

FOOD CONTACT WEBINAR SERIES SCHEDULE
EU Food Contact: Regulation EU 10/2011 for Risk Assessments of Food Contact Materials that
plastic food contact materials fully into force on
01 January 1st 2016 07 Migrate into Food
November 28
October 3

US and Emerging Markets Food Contact China Food Contact Regulations

02 Regulations
October 17 08 December 5

Different Packaging Market: Compliance EU Food Contact Compliance for Paper and Board
03 throughout the Supply Chain
October 24 09 January 9

The Best Approach to Obtain FDA NO Objection

Letter (NOL) for Recycle Plastics and the Recycle EU Food Contact Compliance for Coatings
04 Impact on Lifecycle Analysis 10 January 16
October 31

Dispensing Machines FDA Food Contact GMP for Food Contact

05 Compliance
November 7 11 January 23

Inks and Colorants: Global Food Contact The Impact of the EU NIAS Regulations on the US
Regulations and Migration Studies Designed to
06 Ensure Safe Use in Packaging 12
FDA Final Articles Indirect Food Additives
Compliance
November 14 January 30
26
Register for our webinar series today! http://bit.ly/FC-series
NICHOLAS JERMSTAD

Nicholas.jermstad@intertek.com

intertek.com/regulatory/food-contact/