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					                Children s
                Children’s Oral Exposure to
               Diisononyl Phthalate (DINP) in
               Teethers and Soft Plastic Toys
    Michael A. Babich, Shing‐B
    Michael A. Babich, Shing‐Bong Chen, Michael A. Greene, 
    Mi h l A B bi h Shi            Ch     Mi h l A G
     Celestine T. Kiss, Warren K. Porter, Timothy P. Smith, 
           Marilyn L. Wind, and William W. Zamula
                    U.S. Consumer Product Safety Commission
                                                         January 5, 2011




These comments are those of the CPSC staff, have not been reviewed or approved by, and may not necessarily reflect the views of, the Commission.
                      Children’s
        Phthalates in Children s Products
1980’s
• DEHP primary plasticizer in PVC children s products
                                  children’s
   – Carcinogenic in rats & mice (NTP)
                                    teethers,
   – DEHP voluntarily removed from teethers, rattles, & pacifiers
1990 s
1990’s
                         teethers,
• DINP present in 90% of teethers, rattles, & toys
   – Developmental effects
                                                             U.S.
   – Phthalates voluntary removed from teethers & rattles in U S
   – CPSC petitioned to ban PVC in children’s products
2000’s
• EC b     d    hth l t in hild ’        ti l
      banned 6 phthalates i children’s articles (2005)
   – DEHP, BBP, DBP, DINP, DIDP, DNOP
• U.S. regulates 6 phthalates (2008)

                                                                    2
    Diisononyl Phthalate (DINP)

• Complex substance               O
  – Mixture of isomers
  – Mostly dimethyl heptanols &       OR
    methyl octanols                   OR'
• Two commercial products
• DINP-1 [68515-48-0]
  DINP- [68515-48-                O
           C-    C-
  – C-8 to C-10; C-9 rich
                          DINP-
  – More branching than DINP-2
  DINP- [28553-12-
• DINP-2 [28553-12-0]
                        DINP-
  – Less branching than DINP-1


                                            3
Physico-
Physico-Chemical Properties of DINP
  Molecular formula   C26H42O4
  Molecular weight    418.6 g/mol
  Melting point       -48 C
                       48
  Boiling point       370 C
  Specific gravity    0.97
  Vapor pressure      5 x 10-7 mm Hg
  Water solubility    <0.001—0.2 mg/L
    g
  Log Kow             ~9
                                        4
     Exposure Assessment Approach

• Surveyed soft plastic teethers and toys for DINP
  prevalence and concentration
  Measured DINP migration rates i l b t
• M        d        i ti        t in laboratory
• Lab method calibrated with adult volunteers
                                       0-
• Observation study with 169 children 0-36
  months old
  Probabilistic   l i f       l           by hild
• P b bili ti analysis of oral exposure b child
  age and product type

                                                     5
   DINP Prevalence & Concentration

                        teethers, rattles to s
•Tested 85 soft plastic teethers, rattles, & toys
• 51 were PVC
• 36 contained DINP (42%)
                       13-to-
• DINP concentration 13-to-40% by weight




                                                    6
      Migration f
      Mi ti of DINP i t S li
                    into Saliva

• In 1998, there were many laboratory methods
  – All combined extraction with agitation
    No t d d       t i l               i   to in i
  – N standard materials; no comparisons t i vivo
• RIVM measured migration with adult volunteers
  – Then developed laboratory method that gave
    comparable results
                          (     )
  – Joint Research Centre (JRC) modified the method
    and performed interlaboratory studies
  – Standard disk

                                                      7
             “Head-over-Heels
         JRC “Head-over-Heels” Method
              Head

• Place 10 cm2 sample (disk) in 50 mL saliva simulant
• Rotate at 60 rpm for 30 minutes
  R t t t          f       i t
• Replace simulant & repeat
• Combine both simulant aliquots
                            q
• Measure DINP & calculate migration rate




                                                        8
                                                 In Vitro DINP Migration
                 g/10 cm /minute   12


                                   10
                         /
2




                                    8
Migration rate, µg




                                    6


                                    4
        n




                                    2
M




                                    0
                                        0   10       20        30          40   50

                                                     Percent DINP
                                                                                 9
    In Vivo Migration Studies

• RIVM, Austrian Standards Institute, CPSC
  RIVM A t i St d d I tit t
• 10 Adult Volunteers
• Mouth 10 cm2 PVC disk for 1 h
         15-
  – Four 15-minute sessions
        15-
  – One 15-minute session with Teflon blank
• Standard disk (40% DINP) or toy sample
• Collect saliva, analyze for DINP
    Dubbed “chew and- it”
           “chew- d
  – D bb d “ h -and-spit”
                                              10
             70
                                                 In Vivo DINP Migration
             60


             50
                                                                                   RIVM Standard Disk
     ntage




                                                                                   RIVM Teether
             40
                                                                                   RIVM Teether
Percen




             30                                                                    CPSC Rubber Ducky

             20


             10


              0
                  0-0.49   0.5-0.99   1.0-1.49    1.5-1.99   2.0-2.49   2.5-2.99    3.0-3.49   3.5-3.99   4.0-

                                         Relative Migration Rate
                                         R l ti Mi ti R t
                                                                                                                 11
    Discussion: In Vivo Migration Studies

• DINP absorption through oral mucosa
   – Could underestimate migration
   – Calculated <0.01% of migration rate
• Enzymatic DINP hydrolysis in saliva
   – Could underestimate migration
   – No difference comparing human saliva & saliva simulant
     in vitro
• Differences between adults & children
   – Adults might apply more pressure
   – Could overestimate exposure


                                                              12
               Mi ti D t
               Migration Data
• 42% of Soft plastic toys contained DINP
   – Mean migration rate = 4.1 2.7 g/min (n=24)
   – Migration rate independent of DINP content
• Dutch volunteer (“chew and spit”) study
     Standard        di k ith
   – St d d PVC disk with 40% DINP
   – 19 Adult volunteers—1.17 0.38 g/min
              volunteers—
   – L b t —4 18 0 45 g/min ( 5)
     Laboratory—
     Laboratory 4.18 0.45 / i (n=5)
   – Mean human: lab ratio = 0.28

                                                13
             Observation Study

• 169 Children 3 to 36 months old
• Randomly selected in Chicago and Houston
• Trained observers
•     20-
  12, 20-minute observations over 2 days
• Recorded objects mouthed, frequency and
  duration of mouthing
• Parents recorded time awake, not eating
    – Tday (h) = 9.46 + 0.0375 x Age (months)

                                                14
       Average Daily Mouthing Time
                            (minutes/day)
                               3-11           12-23           24-36
   Object mouthed
                              months          months          months
Number of children               54              66              49

 All except pacifers            70.1            47.4             37
Soft plastic teethers
                                 1.8            0.2              0.2
      & rattles
        p         y
   Soft plastic toys             1.3            1.9              0.8

Mouthing is intermittent. Totals may represent many events.
                            p           g     , g        p
Previous studies used broad product categories, e.g. non-pacifiers

                                                                       15
Daily Mouthing Time for Soft Plastic Toys
              (minutes/day)

   Age      Mean      Median     95 %

 3 – 12
             1.3        0.0       7.1
 months
 12 – 24
             1.9        0.0       8.8
 months
 24 –36
             08
             0.8        0.0
                        00        33
                                  3.3
 months



                                            16
                  M human                 
E   M product             Thour  Tday  B
                  M lab                   
  E, exposure, g/kg-d
  Mproduct, migration rate, g/min
  Mhuman, Mlab, migration rates with standard disk
             hi    i     i     /h *
  Thour, mouthing time, minutes/hour*†
  Tday, exposure time, hours/day*
  B body weight, kg*
  B, b d   i ht k *
       * Depends of child’s age (months)
       † Depends on product category

                                                     17
   Probabilistic Exposure Analysis

      given p
For a g                 g y     g       g ,
            product category & age range,
    randomly select:
1. Mouthing time (min/h) and age (months)
2. Exposure time (h/d), depends on age
3. Product migration rate (g/min) (n=24)
                          (
4. Standard disk migration rate in vivo (n=19)
5. Standard disk migration rate in vitro (n=5)
6 B d weight (kg), d
6. Body                     d
            i h (k ) depends on age
7. Calculate exposure. Return to step 1.

                                                 18
              from Soft Plastic Toys (g/kg-d)*
DINP Exposure f      f l                /k
                                     (g/kg-


   Age          Mean          95%          99%

  3 – 11         0.07          0.44          1.4
  months     (0.03-0.13)   (0.15-0.82)   (0.74-2.4)
  12 – 23        0.08          0.53          1.5
  months     (0.04-0.14)
             (0 04 0 14)   (0.24-0.89)
                           (0 24 0 89)   (0 89 2 3)
                                         (0.89-2.3)
  24 – 36        0.03          0.12         0.56
    o t s
  months     (0 0 0 06)
             (0.01-0.06)   (0.04-0.23)
                           (0 0 0 3)     (0      6)
                                         (0.17-1.6)

*42% contain DINP


                                                      19
                                             Toys,
Hypothetical DINP Exposure from Soft Plastic Toys
        Teethers, and Rattles (g/kg-d)*
                              (g/kg-

   Age         Mean            95%        99%

  3 – 11        0.45          2.2          4.9
  months     (0.24-0.74)   (1.2-3.5)    (2.6-7.4)
  12 – 23        0.22          1.1         2.4
  months     (0.12-0.34)
             (0 12-0 34)   (0.64-1.7)
                           (0 64-1 7)   (2.6-7.4)
                                        (2 6-7 4)
  24 – 36        0.08         0.33         1.6
  months     (0.02-0.18)   (0.12-1.1)   (0.27-3.1)


*Assuming 100 % contain DINP


                                                     20
                    Conclusions

• Estimated exposures << the ADI (120 g/kg-d)
                                            g/kg-
                teethers,
• DINP in toys, teethers, and rattles is not hazardous
  to children
• CPSC denied the petition to ban PVC in children’s
  products (2003)
• However, we studied one phthalate (DINP) & one
                    (teethers,
  class of products (teethers, rattles, & toys)




                                                     21
Consumer Product Safety Improvement Act
      of 2008 (CPSIA) Section 108
  • Effective February 2009
  • Permanent Ban
     – DBP, BBP, and DEHP (>0.1%)
     – Children’s toys and child care articles
    Interim Ban—Pending Review b CHAP
            B
  • I t i Ban—P di R i             by
     – DINP, DIDP, DNOP (>0.1%)
       Children s                              child s
     – Children’s toys that can be placed in a child’s
       mouth and child care articles
  • CHAP on Phthalates & Phthalate Substitutes

                                                         22
  Chronic Hazard Advisory Panel

• Convened in April 2010
• Cumulative health risk assessment
  –   All phthalates & phthalate substitutes
  –   All sources and products
  –   All routes of exposure
  –   Children, expectant mothers, others
  –   All health endpoints
• Final report 2012

                                               23
            For More Information
• Michael Babich — mbabich@cpsc.gov
                    mbabich@cpsc gov
• 2010 CHAP on Phthalates & Phthalate Substitutes
     p        p g              p
  http://www.cpsc.gov/about/cpsia/sect108.html
• 2002 Staff Risk Assessment
   – www.cpsc.gov/library/foia/foia02/brief/briefing.html
           Tox.            151-       (2004)
   – Reg. Tox. Pharm. 40: 151-167 (2004)
• 2001 CHAP Report on DINP
  http://www.cpsc.gov/library/foia/foia01/os/dinp.pdf
  http://www cpsc gov/library/foia/foia01/os/dinp pdf



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