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Federal Register / Vol. 86, No. 193 / Friday, October 8, 2021 / Rules and Regulations
contentions 12.24b2. Therefore, in the absence of any other evidence, studies, or new scientific information addressing the flaws identified in the Moore study that would demonstrate that the use of lead acetate in hair dye is safe, we are denying the request for a hearing on this objection.
C. Category C: ConsExpo In Silico Computer Modeling Combes numbered objections included in Category C are as follows:

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9. Combe objects to FDAs reliance on a novel and unvalidated computer model.
10. Combe objects to FDAs treating an unvalidated computer model as more reliable than robust human data.

Objection 9. Combe objects to FDAs reliance on a novel and unvalidated computer model. Combe states that FDA failed to explain whether the model is validated and why it used this particular model. See Submission, page 39. Combe further claims that FDA
never explained the details of the model, how the math works, or why FDAs inputs to the model are reasonable. Ibid.
Response to Objection 9 Contrary to Combes contention, the ConsExpo dermal absorption model is not novel.
The ConsExpo dermal absorption model is a mathematically based modeling program that enables general estimation of human exposure to chemicals found in consumer products via inhalation, skin absorption, and oral intake. The description of the basis of the ConsExpo dermal absorption model was first published in 1996 Ref. 13. The program was developed by the Netherlands National Institute for Public Health and the Environment RIVM and is available to the public.
The program updates are now released by RIVM in collaboration with other European counterpart institutes, including the French Agency for Food, Environmental and Occupational Health and Safety, the German Institute for Risk Assessment, the Federal Office of Public Health Switzerland, and Health Canada. This model has been used by other regulators e.g., Health Canada and has been cited in various scientific publications, as listed in Appendix 6 of the Wyatt memorandum Refs. 2 and 14.
In the Wyatt memorandum Ref. 2, Appendices 4 to 6, and in the October 31, 2018, final rule 83 FR 54665 at 54670, we explained our decision to use the in silico modeling to predict the percentage of dermal absorption of lead by the surface area of the full human scalp and all the parameters and inputs to the model. We chose to use in silico
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modeling because, as described in our response to Objection 7, we had identified several flaws in the Moore study design that resulted in the underestimation of lead exposure from this intended use.
Using EPAs Kp value for lead acetate,6 we used the ConsExpo dermal absorption modeling software to estimate absorption based on the intended conditions of use including the relevant lead concentration, surface area, and duration of application period. As stated in Appendix 4 of the Wyatt memorandum Ref. 2, we also performed an internal validation by applying parameters identical to experimental conditions used in the Moore study into the ConsExpo dermal absorption model. The model successfully predicts Moores experimental results using Moores study parameters from experimental conditions, which can be taken as evidence of validation of the model. We believe that no further validation is needed for the purpose of using the model to fill gaps in experimental data.
The objection failed to include any new information or data that would refute our conclusion that the ConsExpo dermal absorption model was appropriate to use in the manner that we applied it. A hearing will not be granted on the basis of general descriptions of positions and contentions 12.24b2. The objector must, at a minimum, raise a material issue concerning which a meaningful hearing might be held. Therefore, we are denying the request for a hearing on this objection.
Objection 10. Combe objects to FDAs treating an unvalidated computer model as more reliable and robust than human experimental data.
In this objection, Combe insists that the computer model is not needed because human data are available and that it is unscientific for a computer model to be used to trump robust human data. See Submission, page 40.
Response to Objection 10 FDA
agrees that human studies, when scientifically well-designed and conducted, provide more robust and reliable data than computer modeling in the safety evaluations of color additives.
As discussed in the Wyatt memorandum and in the October 31, 2018, final rule 83 FR 54665 at 54668 through 54672, we reevaluated the Moore study and identified significant scientific flaws.
Based on this reevaluation, our current 6 Kp is a chemical-specific absorption-related constant that is independent of the surface area, concentration, etc. see further description of Kp in our response to Objection 12.

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thinking regarding the radioactive tracer skin absorption study conducted by Moore et al., is that it is no longer possible to rely on this human data because of these significant flaws.
Consequently, we no longer consider it scientifically sound to continue the use of the experimental fractional absorption number derived from this study when the experimental conditions are not consistent with the intended conditions of use for the hair dye product. We believe that the flaws in the Moore study may have resulted in underestimating the exposure to lead from lead acetate-containing hair dye.
We also believe that it is scientifically valid and appropriate to use the in silico computer model to extrapolate and predict the absorption to fill the data gaps created by the absence of data from human experimental studies designed and conducted to simulate the intended conditions of use for lead acetatecontaining hair dye.
In this objection, Combe did not provide any information to address the significant flaws in the Moore study that we identified. This objection also failed to identify any other human studies that we could consider in lieu of the in silico computer model. Therefore, we are denying the request for a hearing on this objection.
D. Category D: Skin Permeability Coefficient Combes numbered objections included in Category D are as follows:
12. Combe objects to FDAs reliance on a permeability coefficient for lead instead of fractional absorption.
13. Combe objects to FDAs use of a permeability coefficient for lead acetate that EPA repudiated and replaced with a much lower estimate.

Objection 12. Combe objects to FDAs reliance on a permeability coefficient for lead instead of fractional absorption. Combe argues that FDA has not demonstrated that the ConsExpo dermal absorption model has been validated for inorganic substances such as lead, and that FDA does not explain how the permeability coefficient for lead acetate was derived and whether it is appropriate for use in the model. See Submission, page 44. Combe further asserts that we are relying on an outdated permeability coefficient from EPA. See Submission, pages 4344.
Because this last argument is also the subject of Objection 13 see Submission, page 45, we will respond to this assertion in our response to Objection 13 below.
Response to Objection 12 There are two ways to calculate skin absorption for exposure assessments: 1 The use of
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