Talcum Powder & Ovarian Cancer

Targeting African American & Hispanic Women

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Targeting Obese & “Curvy” Women

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P-125

Case-Control and Cohort Studies (All Ovarian) (1982-2016)

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Case-Control and Cohort Studies (All Ovarian) (1982-2016)

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Meta-Analyses and Pooled Studies (All Ovarian)

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Meta-Analyses and Pooled Studies (All Ovarian)

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Health Canada Causal Assessment

Reviewed epidemiologyReviewed all animal studiesReviewed all in vitro and other mechanistic studiesAssumed no asbestos in talcum powder products

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The meta-analyses of the available human studies in the peer-reviewed literature indicate a consistent and statistically significant positive association between perineal exposure to talc and ovarian cancer. Further, available data are indicative of a causal effect. (P.iii)

PresenterPresentation NotesFormerly known as the Cosmetic, Toiletry and Fragrance Association (CTFA) until 2007, when name was changed to Personal Care Products Council (PCPC)

Penninkilampi (2018)

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“The results of this review indicate that perineal talc use is associatedwith a 24%–39% increased risk of ovarian cancer. While the results ofcase–control studies are prone to recall bias, especially with intensemedia attention following the commencement of litigation in 2014,the confirmation of an association in cohort studies between perinealtalc use and serous invasive ovarian cancer is suggestive of a causalassociation.”

GC Opp. Ex. 62)

Opinions Shared: Congressional Testimony

March 12, 2019: Hearing on Health Risks of Carcinogens in Consumer ProductsHouse Committee on Oversight and Reform

Subcommittee on Economic and Consumer Policy

• My review identified 38 high-quality epidemiologic studies conducted over the past 40 years. These studies asked women about their use of talcum powder products in the genital area, and tested associations with risk of ovarian cancer. Together, these studies included over 14,000 women with epithelial ovarian cancer (the most common type) and an even greater number of women without ovarian cancer.

• Summarizing data from all of the published studies consistently shows that women who had ever used talcum powder products in the genital area had a statistically significant 22-31% increased risk of developing epithelial ovarian cancer compared with women who had never used them.

• These combined analyses showed that increasing amount of exposure to talcum powder products in the genital area resulted in increasing risk of developing epithelial ovarian cancer.

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Constituents in Johnson’s Baby Powder & Shower to Shower

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CONSTITUENTS IN BABY POWDER

NUMEROUSKNOWN OR SUSPECTED

CARCINOGENS

The constituents shown below are found in Johnson’s Baby Powder and Shower to Shower.

Fibrous talc and asbestos documented in Drs. Longo, Cook & Krekeler’s Reports. (Asb. Opp. Exs. 67, 120, 119). Metals documented in Pier Ex. 47 and Drs. Cook and Krekeler’s reports. Fragrance chemicals analyzed in Dr. Crowley’s report. (HM Opp. Ex. 10).

PLATY TALC

• Inflammatory• Fibrogenic• 2B carcinogen (IARC)

FIBROUS TALC

• Inflammatory; genotoxic• Direct & indirect genotoxicity• Group 1 carcinogen (IARC)

ASBESTOS

• Frequently present• Direct & indirect genotoxicity• All forms are Group 1 (IARC)

COBALT

• Found in BP & S2S• Oxidative stress• 2B carcinogen (IARC)

NICKEL

• Found in BP & S2S• Induces DNA damage• Group 1 carcinogen (IARC)

FRAGRANCE CHEMICALS

• Toxins & irritants• Carcinogens – styrene (2A), and

coumarin, eugenol, and d-limone (2B)

Ni

Co

CHROMIUM

• Found in BP & S2S• Inflammation, OS, DNA damage• Group 1 carcinogen (IARC)

Cr

Defendants’ Internal Testing Document Asbestos

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Testing of Historical Samples

Drs. Longo & Rigler Samples produced pursuant to MDL Order66% of historical samples have tested positive for asbestos99% of historical samples have tested positive for fibrous talc

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FDA Finds Asbestos in Johnson’s Baby Powder

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FDA Identifies Chrysotile Asbestos in JBP

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FDA Identifies Fibrous Talc in JBP

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The Impact of Fibers on Carcinogenesis

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Genotoxicity

Inflammation

Fibrous Talc(Ms. Brower P-5601B)

INDIRECT• Oxidative stress• Epigenetic alterations• Actuation of signaling

pathways• Resistance to apoptosis• Stimulation cell

proliferationCarcinogenesis

DIRECT• DNA breaks &

oxidized bases in DNA

• Fibers interfere with mitotic apparatus by direct physical interaction

Platy TalcPlaty Talc(Shukla - P-690)

INDIRECT• Oxidative stress• Epigenetic alterations• Actuation of signaling

pathways• Resistance to apoptosis• Stimulation cell

proliferation

Cell Studies

Study Cell Lines Dose Time FindingsShukla (2009)(GC Opp. Ex. 93)

• Immortalized ovarian mesothelial cells• Mesothelial cells

0, 1, 5, 10, 20, 75 µg/cm²

8 hrs.24 hrs.

• Gene up-regulation

Buz’Zard (2007)(GC Opp. Ex. 94)

• Immortalized normal ovarian epithelial cells

• Immortalized normal ovarian epithelial cells

0, 1, 5, 10, 15, 20, 50, 100, 500 µg/cm²

24 hrs.72 hrs.

• Proliferation• Neoplastic transformation• Increased ROS

Akhtar (2010)(GC Opp. Ex. 96)

• Lung adenocarcinoma 1, 50, 100, 200 µg/mL

48 hrs. • Oxidative stress

Akhtar (2014)(GC Opp. Ex. 95)

• Lung epithelial cells 0, 200 µg/mL 48 hrs. • Cytotoxicity• Oxidative stress• Apoptosis

Fletcher, Saed (2019) (GC Opp. Ex. 97)

• Ovarian cancer cells A2780• Ovarian cancer cells SKOV-3• Ovarian cancer cells TOV112D• Normal macrophage cells• Primary normal ovarian epithelial cells• Immortalized ovarian epithelial cells• Immortalized fallopian tube cells

0, 5, 20, 100 µg/mL

72 hrs. • Change in redox balance• Increased CA-125• Increased cell proliferation• Decreased apoptosis• SNPs

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Fall-Out from FDA Testing

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J&J recalls 33,000 bottles of Johnson’s Baby PowderRetailers such as CVS, Walmart, Target, Rite Aid remove Johnson’s Baby Powder with talc from shelvesJohnson & Johnson announced yesterday that it will no longer manufacturer Johnson’s Baby Powder with talc in the United States.

MDL Overview

U.S.D.C. (Trenton, NJ)• Judge Freda Wolfson

15,500+ plaintiffs in MDL• 2,000+ state court cases nation-wide:

NJ, CA, IL, MO, GA, FL, PA

Case-specific discovery has not commencedDaubert Hearing – July 22-31• 5 Plaintiffs experts• 3 Defense experts

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Upcoming State Trials

City of St. Louis, Missouri• Forrest case set for trial December 2019• Other trials expected during the first half of 2020Illinois state court: Driscoll case set March 2020Superior Court of New Jersey (Atlantic City)• Mesothelioma - $37.5 million compensatory verdict with punitive phase to be

scheduled soon • Ovarian Cancer - Oral Argument in the appeal of summary judgment order set

for October 24, 2019 - Richard Golomb and Chris Placitella arguing

Philadelphia: Kleiner case set for March 2020Florida: Matthey case set for April 2020Numerous mesothelioma cases set for trial throughout 2020

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Talcum Powder & Ovarian Cancer

Slide Number 1Targeting African American & Hispanic WomenTargeting Obese & “Curvy” WomenCase-Control and Cohort Studies (All Ovarian) (1982-2016)Case-Control and Cohort Studies (All Ovarian) (1982-2016)Meta-Analyses and Pooled Studies (All Ovarian)Meta-Analyses and Pooled Studies (All Ovarian)Health Canada Causal AssessmentSlide Number 9Opinions Shared: Congressional TestimonySlide Number 11Defendants’ Internal Testing Document AsbestosTesting of Historical SamplesFDA Finds Asbestos in Johnson’s Baby PowderFDA Identifies Chrysotile Asbestos in JBPFDA Identifies Fibrous Talc in JBPSlide Number 17Cell StudiesFall-Out from FDA TestingMDL OverviewUpcoming State TrialsSlide Number 22