AIHA Fall Conference Template

The Chartered Society for Worker Health Protection

OH2016 25 - 28 April 2016 Glasgow, Scotland Session 3c

Nanotechnology Tuesday, April 26, 2016

Nanoscale Titanium Dioxide in Cosmetics: Is Everything Beautiful?

Jacob Persky, MPH, CIH Fred W Boelter, CIH, PE, BCEE, FAIHA

RHP Risk Management Inc.

Exposure Science

Law Policy

Regulations

Business

Technology

Product Safety Cosmetics & Personal Care Products

Manufacturing

Titanium Dioxide in Cosmetics

REACH DNELs EU cosmetics directive

FDA USP NIOSH REL

Prop65 NSRL

Listing published January 2011 WHO/IARC – Group 2B (possibly carcinogenic to humans)

Prop Listing applies to: “Airborne, unbound particles of respirable size”

Listed in 2011

Violation Notice Issued in 2013

No Significant Risk

CALIFORNIA PROPOSITION 65 WARNING

WARNING: This product contains chemicals known to the State of

California to cause cancer.

Regulatory Requirement Options:

• Reformulate • Remove from Commerce

• Hazard Warning Label • Risk Determination

California Office of Environmental Health Hazard Assessment

Warning label exemption if exposure from typical product use poses no significant risk of cancer. Meaning: • < 1 excess cancer in 100,000 individuals exposed over a

70-year lifetime. (<1E-5) • Regulations identify specific “No Significant Risk Levels”

(NSRLs) for many listed carcinogens… but not TiO2

Cancer slope factor Epidemiology

Toxicology

Exposure Science

Derive NSRL Conduct Quantitative Exposure Assessment

Definition of “No Significant Risk”

Detection. The first hurdle.

• Exposure Assessment: Detectable?

“Knowingly and intentionally exposed persons to a listed chemical without providing clear and reasonable warning.”

• Must demonstrate prima facie exposure potential.

When bringing action against a manufacturer, it is the plaintiff’s burden to demonstrate exposure is detectable. This is not a risk-based approach, it is a function of analytical methodology and LODs.

Yes. Use risk-based approach.

No. No action required.

Exposure Assessment Challenge

Develop an exposure assessment strategy which will withstand scientific scrutiny, absent a NSRL criterion value.

No “knowing and intentional exposure” occurs if: • A method of detection and analysis is applied

concerning an alleged exposure. • Methods of detection and analysis that may be

relied on include: FDA, USEPA, OSHA, NIOSH, CPSC, etc.

• Select “most sensitive” method of detection / analysis • All reported results must show that the chemical

in question was not detected.

Criteria

Most Sensitive Validated Method

NIOSH REL 2.4 mg/m3

for fine TiO2

0.3 mg/m3 for ultrafine TiO2

RISK at REL

1 in 1,000 excess cancer risk criteria • 8-hr TWA

• ≤10 hours/day • 40 hours/week

• 45 year working lifetime

NIOSH Method 7300. ICP-AES RL = < 0.000834 mg/filter

April 2011

Cancer Risk Time Adjustment NIOSH REL Parameters • Occupational • 40 hrs/week

• 45 yr working lifetime exposure duration

• Acceptable risk level at 1:1,000

NSRL Derivation Parameters • Consumer Product Use • ~4 minutes per application;

0.3-1.3 applications per day (face-powder) (0.1 – 0.6 hrs/week)

• 70 yr life expectancy

• Acceptable risk level at 1:100,000

Collect two side-by-side respirable dust samples. One on a PVC filter and the other on a MCEF filter.

START

Analyze the PVC filter by both gravimetric (NIOSH

0600) and ICP-AES (NIOSH 7300) methods.

No further action.

Analyze duplicate MCEF sample by electron microscopy (TEM) for

TiO2 particle size distribution.

Determine mass TiO2 concentration of fine and ultrafine.

Respirable TiO2 detected.

Respirable TiO

2 not detected.

Product Categories

Assessed application-related exposures to 5 products representing 4 consumer product categories.

Eye Shadow

Face Powder

Sunscreen powder Nail Powder

Blush

Exposure Assessment Chamber

• Study conducted in 10’x17’x8’ isolation room.

• Protect testing environment from outside interferences.

• Dressing table with mirror and chair for product application.

• HEPA-filtered air to purge room air between test scenarios. (off during testing)

Strategy: Respirable Particulate

• Task duration, personal breathing zone air sampling.

• 2 side-by-side samples with particle-size selective samplers (BGI GK 2.69 cyclone) attached to filter-cassette. – Sample #1

Respirable fraction of airborne dust. NIOSH 0600 – Respirable dust. NIOSH 7300 – Total titanium as TiO2.

– Sample #2 Respirable fraction of airborne dust. Electron microscopy for particle size distribution analysis.

Study Participants Participant A

– Industrial hygienist

– Uses consumer products

– Subject for eye shadow, face powder, blush, and sunscreen tests.

Participant B

– 25-yr salon professional

– Uses products personally

– Applies product professionally

– Nail powder test subject

Eye Shadow

Face Powder

Blush

Sunscreen

Nail Powder

Product Mass Balance Pre- and post-application mass measurement of

product container and applicator.

Gravimetric Results for Respirable Dust (NIOSH 0600)

All results “Non-Detect”. Results shown as < Reporting Limit.

Test Replicate

Eye Shadow (mg/m3)

Face Powder (mg/m3)

Blush

(mg/m3)

Sun Screen (mg/m3)

Nail Powder (mg/m3)

A < 1.70 < 1.70 < 2.38 < 1.08 < 0.178

B < 1.70 < 1.19 < 2.38 < 1.32 < 0.265

C < 1.70 < 1.70 < 1.70 < 1.32 < 0.313

D -- -- < 1.70 -- --

Differences in reporting limits within and across products reflect variability in duration of product application and difference in the total sampling time.

ICP-AES Results for Respirable TiO2 (NIOSH 7300) §

All results “Non-Detect”. Results shown as < Reporting Limit.

Test Replicate

Eye Shadow (mg/m3)

Face Powder (mg/m3)

Blush

(mg/m3)

Sun Screen (mg/m3)

Nail Powder (mg/m3)

A < 0.0284 < 0.0284 < 0.0397 < 0.0181 < 0.00296

B < 0.0284 < 0.0199 < 0.0397 < 0.0221 < 0.00441

C < 0.0284 < 0.0284 < 0.0284 < 0.0221 < 0.00523

D -- -- < 0.0284 -- --

Difference in reporting limits within and across products reflect variability in the duration of product application and difference in the total sampling time. § Values shown are mass-balance adjusted to represent TiO2 concentrations based upon elemental Ti analysis.

Conclusions

• Exposure assessment study design absent a criterion for data interpretation presents a significant challenge.

• A defensible exposure assessment strategy may be developed based upon relevant toxicological data coupled with realistic exposure factors.

• Risk-assessment is translatable. i.e. Prop65 exposure assessment that meets data quality objectives may find application to REACh.

Thank You.

Jacob Persky, MPH, CIH RHP Risk Management Inc. Chicago, Illinois, USA jpersky@rhprisk.com +1 773 867 6001

Fred W Boelter, CIH, PE, BCEE, FAIHA RHP Risk Management Inc. Boise, Idaho, USA fboelter@rhprisk.com +1 208 258 7478

Presenters note: Mr. Persky was the Project Manager for this TiO2 study while both he and Mr. Boelter were employed by ENVIRON International Corporation.