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Federal Register / Vol. 86, No. 193 / Friday, October 8, 2021 / Rules and Regulations
guidance recommends, in part, that the test article should be applied to the part of the body and maximal skin surface areas that are consistent with the final products intended skin surface area use Ref. 8, page 6.
By contrast, the Moore study design where the lead acetate formulation was applied to a small surface area on the foreheaddid not reflect either where lead acetate hair dye is intended to be applied or the surface area of such application. Specifically, in the Moore study, the lead acetate formulation was tested on only a small fraction of the skin surface area i.e., 8 to 10 square centimeters cm2 on the forehead instead of approximately 580 cm2 for the full scalp. Additionally, the test formulation was applied to an area of skin without many hair follicles, which may have further underestimated the amount of lead absorbed. Lead absorption was measured after 12 hours and 24 hours of exposure, and the test formulation was washed off after the first 12 hours. The study did not investigate the actual directions of use of this hair dye, which results in accumulation of lead on the hair and skin. 5 Therefore, the Moore study underestimated exposure to lead from the use of lead acetate hair dyes. Based on these flaws and the additional flaws we identified in the Moore study, specifically, the formulation used in the study contained 0.12 to 0.18 percent lead instead of 0.6 percent, the ages of the eight male test subjects range from 20 to 35 years instead of older adults, and the short duration of test article application, which were discussed in detail in the final rule that appeared in the Federal Register of October 31, 2018
83 FR 54665 at 54668 through 54670, we stated that the Moore study results could no longer be relied on to make a safety decision for the use of lead acetate as a color additive in hair dye.
Therefore, considering the reported adverse effects at low levels of lead exposure e.g., increased blood pressure, hypertension, decreased glomerular filtration rate 83 FR 54665 at 54668, and the absence of data showing a safe level of lead exposure, we believe that the safety standard of reasonable certainty of no harm is no longer met.
Because Combe has not provided new data that address the identified flaws in the Moore study, we conclude that Combes argument on the Moore study is insufficient to justify a hearing 5 The manufacturers use directions state that after the initial application, users might apply the progressive hair dye daily until the desired color shade is achieved usually takes 23 weeks, and then once or twice a week to maintain the hair color.

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12.24b3. Therefore, we are denying the request for a hearing on this objection.
Objection 7. Combe objects to FDAs criticisms of Moore. Combe states that in 1981, FDA concluded that Moores radioactive tracking study demonstrated a miniscule amount of lead absorption from lead acetate hair dyes. See Submission, page 35. Combe further states that the Moore study result of 0.058 percent is supported by a subsequent study by Bress and Bidanset Ref. 2, which estimated absorption of lead acetate as 0.05 percent. See Submission, at page 37.
Response to Objection 7 We acknowledge that, based on the scientific information available 40 years ago, we considered the 1978 radioactive tracer skin absorption study sponsored by Combe a petitioner for CAP 3C0107
and conducted by Moore et al.
published in 1980 to be the primary study supporting the approval of lead acetate as a color additive in 1980, and that it was applicable for studying human skin lead absorption at that time.
However, as discussed in our response to Objection 6 and the October 31, 2018, final rule 83 FR 54665 at 54668 through 54670, we have since identified several flaws in the Moore study design and conduct, such as applying test formulation with a lower lead concentration, on a smaller surface area of skin, and for a short period of time, when compared to the intended conditions of use. For example, as discussed previously, Moore et al.
applied the lead acetate-containing formulation to an 8 to 10 cm2 surface area on the forehead without many hair follicles, which is not consistent with the intended condition of use for the hair dye product on the full scalp with many hair follicles and a skin surface area of approximately 580 cm2, thereby underestimating the exposure to lead from lead acetate-containing hair dye. In addition, the result of 0.058 percent was measured 12 hours after a single application of the hair dye, which was then washed off. Therefore, the result does not represent the accumulation of lead from daily use of the hair dye.
Because of these identified flaws and others described in the response to Objection 6, the fractional absorption calculated from the Moore study does not accurately represent the actual dermal absorption under the intended conditions of use, and therefore does not support the safe use of lead acetate in progressive hair dyes.
We also reviewed the study published in 1991 by Bress and Bidanset Ref. 2.
While the results from this study are consistent with those from the Moore
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study, Bress and Bidanset also applied the lead compound to a small skin surface area; thus, their study is of similar limited utility as the Moore study because it may also underestimate the exposure to lead from the use of hair dye. The objection failed to provide new data that address the identified flaws in the Moore study and the limitation of the Bress and Bidanset study for estimating skin absorption of lead from the use of lead acetate hair dye, and the information discussed in this objection is insufficient to justify a hearing 12.24b3. Therefore, we are denying the request for a hearing on this objection.
Objection 8. Combe objects to FDAs finding that the lead in the Moore study could have been absorbed by other parts of the body than the blood. Combe also states that the radioactive tracer skin absorption study conducted by Moore et al. measured whole body lead including lead in the blood, other fluids, tissues, muscle, and bone and that Moore et al. calculated that 40
percent of the lead absorbed by the whole body was absorbed into the blood. See Submission, page 38.
Response to Objection 8 In a March 3, 1978, final rule postponing the closing date for the provisional listing of lead acetate for use as a component of hair colors 43 FR 8790, we stated that the radioactive tracer skin absorption study protocol submitted to FDA would measure whole body counts of lead absorption, and in addition, blood and urine samples would be analyzed for measurable levels of lead 43 FR 8790 at 8793. However, as further discussed in our response to Objection 12, the use of fractional absorption to express dermal absorption depends on the study design e.g., duration of exposure, how much of the test material is in contact with a given surface area, the concentration of the substance in the matrix. Also, as stated in our response to Objection 6, given its fundamental flaws, the Moore study underestimated exposure to lead from the use of lead acetate hair dyes.
Therefore, we can no longer rely on this studys exposure estimate to assure the safe use of lead acetate in hair dye.
Combe does not point to any other studies that have evaluated lead absorption across the full surface area of the scalp, nor does Combe point to other studies demonstrating an absorption estimate after correcting the flaw in the Moore study that could provide evidence that the use of lead acetate in hair dye is safe.
A hearing will not be granted on the basis of mere allegations or general descriptions of positions and contentions 12.24b2. Therefore, in
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