Can Coatings Primer and Safety Assessment: Communicating Evidence of Absence

Conflict of Interest Statement

Mark Maier is currently a paid consultant and former employee of the Valspar Corporation. This educational presentation is made solely by and on behalf of Sheperian Toxicology, LLC who is responsible for its content. Mark Maier received no compensation from Valspar Corporation for this work.

Fair Use Notice Graphics in this presentation are/were publicly available and are used solely for educational purposes and may not be used otherwise. Source credit is given for graphics in this presentation when available.

Different Cans, Different Coatings

Food & Beverage Ends‒Coil Coating

National Coil Coating Assn

Valspar Corp.

Food Can Manufacturing Two Piece

Side Seam Three Piece

Beverage Can Multi-Step Engineering Marvel

“Engineer Guy” Bill Hammack, Univ. Illinois The Ingenious Design of the Aluminum Beverage Can

YouTube: https://www.youtube.com/watch?v=hUhisi2FBuw

Demands Placed on Coatings

“Engineer Guy” Bill Hammack, Univ. Illinois The Ingenious Design of the Aluminum Beverage Can

Beverage Can Manufacturing

Crown Beverage Packaging, Inc.

Visy Industries Holdings Pty Ltd

Beverage Can Ends

Han, J. et al. Appl. Erg 2008. 39: 150

Pressco Technology , Inc.

Pressco Technology Inc.

End Punched

from Coated

Coil

Tooling and Riveting

Coating must maintain seal after tooling and riveting

Migration from Film

INCDTIM Romania

Migration Chromatogram

Innovations in Food Safety, Shelf Life and Food Safety

If BPA is Replaced, What Choices are Available?

Acrylic Vinyl Oleo PE 1 PE II

Beverage End

Beverage Body 3PC Food Food D&I Food

DRD Food End Food EZO Closure

BPA BASED EPOXY

Wish List for BPA Replacement Coating

1. Epoxy Performance–must be epoxy chemistry

2. No estrogenic monomers

3. Total Migration–< 50 ppm (0.5 mg/in2); < 1,000 Da.

4. Specific Migrations–< 0.5 ppb (TTC-based)

5. Industrial Scale Raw Materials

6. Acceptable cost

Step 1 Find New Materials

Valspar Corp

Valspar Corp

Most New Coatings were Made Using Pre-Authorized Materials Listed “in the Box”

Epoxy Monomers in the Box were Estrogenic

New Molecules Were Needed

Performance vs. Hazard

Chemical Reactivity

No Biological Hazard

Molecules were Needed that React with Each Other

…but physiologically, do…

…And

What Can be Learned from BPA Epoxy?

C. 4,4'-methylenediphenol functionality found in BPA is essential

A. Bisphenol A is estrogenic in vitro 1

2

B. There are two sources of BPA in the polymer synthesis

A. Is There a Non-Estrogenic Bisphenol?

Bisphenols are the only commercially viable source for 4,4'-methylenediphenol functionality.

BPA

B. Could the Bisphenol be Taken Out of the Last Step?

C. V70 Route of Synthesis

4,4'-methylenediphenol functionality

Why Should People Believe these Molecules are Safe?

Just because I said so?

Prescriptive Approaches were Tried

defa

ult

Force Fit

Green Screen TI

PED

co

ntra

dict

misunderstand

Excessive

Keeping in Mind Reactants ≠ Products

≠

≠

Sodium

Chlorine

GreenScreen®

Designing endocrine disruption out of the next generation of chemicals. Schug et al. Green Chem., 2013,15, 181-198

“While in silico and in vitro assays offer less costly starting points, in vivo assays are necessary to conclude that a

chemical is unlikely to have EDC activity.” http://www.tipedinfo.com/tiped_tier/guiding-principles/

?

Tiered Protocol for Endocrine Disruption (TiPED)

defa

ult

Force Fit

Green Screen

TIPE

D

cont

radi

ct

misunderstand

Excessive

Do Your Own Science First Table III. Summary of analysis and assay results for ER (read-across target) and read-across sources TMBPFDGE, BADGE, NOGE and oligo-BFDGE.

Green = Negative experimental result, Red = Positive experimental result RA = Read-across (only applies to “target” substance, ER) ND = no data available Numbers indicate relative potency in the standard Ames assay (Table IV)

ER TMBPFDGE BADGE NOGE oligo-

BFDGE In vitro

MLA -S9 culture ND MLA +S9 culture ND

TA-98 -S9 plate TA-100 -S9 plate

TA-1535 -S9 plate TA-1537 -S9 plate

TA-98 +S9 plate TA-100 +S9 plate 3.9 4.7 25.0

TA-1535 +S9 plate 33.6 35.5 117.8 TA-1537 +S9 plate

Mutagenicity CAESAR Model Model Model Model Model Model TA-98 -S9 mpf RA ND ND ND

TA-100 -S9 mpf RA ND ND ND TA-1535 -S9 mpf RA ND ND ND TA-1537 -S9 mpf RA ND ND ND

TA-98 +S9 mpf RA ND ND ND TA-100 +S9 mpf RA ND ND ND

TA-1535 +S9 mpf RA ND ND ND TA-1537 +S9 mpf RA ND ND ND

GS GADD45 -S9 culture RA ND ND ND GS GADD45 +S9 culture RA ND ND ND

In vivo

Micronucleus Oral Oral Oral ND Oral Comet Assay or other DNA damage Oral Oral Oral Oral Oral

Chromosomal aberration RA ND Oral Oral Oral

Transgenic Mouse RA ND ND Oral

Carcinogenicity RA ND ND Dermal

Carcinogenicity Model Model Model Model Model Carcinogenicity QSAR QSAR QSAR QSAR QSAR

Repeated Oral Dose (mg/kg-bw/d)

28-56Day NOAEL = 100 LOAEL = 300 Repro/Dev

NOAEL = 300

ND

Chronic NOAEL = 15

Subchronic NOAEL = 50; LOAEL = 250

ND

90-Day NOAEL = 250 (limit dose)

14-day NOAEL =

300; LOAEL = 1000

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(Listing does not necessarily imply endorsement, approval, or further discussion)

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Regulatory

Ask for Help

Then… Let Your Best Critics Review Your Work, do Their Own, and Try to Prove You are Wrong.

Go Beyond …

Female mammary glands (right side) were whole-mounted for three-dimensional inspection

Terminal end buds, branching, budding and ductal extension were examined; lymph node was used as point of reference

Qualitative analysis – Absence – Minimal – Slight – Moderate – Marked – Abundant

Go Beyond …

Extract

Concentration

References

“Engineer Guy” Bill Hammack, Univ. Illinois. The Ingenious Design of the Aluminum Beverage Can. https://www.youtube.com/watch?v=hUhisi2FBuw

Soto AM, Schaeberle C, Maier MS, Sonnenschein C, Maffini MV. Evidence of

Absence: Estrogenicity Assessment of a New Food-Contact Coating and the Bisphenol Used in Its Synthesis. Environ Sci Technol. 2017 Feb 7; 51(3):1718-1726.

Acknowledgements

Tom Mallen, Ronnie Weaver, and everyone at Valspar

Maricel Maffini–Independent Consultant Ana Soto Lab–Tufts University Food and Beverage Brand Owners Can Makers …and

…Talented Scientists & Engineers from these Organizations (Listing does not necessarily imply endorsement or approval)

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