Voglio sapere a riguardo di…

Federal Register / Vol. 86, No. 243 / Wednesday, December 22, 2021 / Rules and Regulations Munro and Kroes Munro et al. 1996 to establish generic threshold values for human exposure at which a very low probability of adverse effects is likely.
By comparing a range of compounds by their structure using the Cramer classification scheme, i.e., Cramer Class Cramer et al. 1978, and NOEL noobserved-effect-level, fifth percentile NOELs were established for each Cramer Class as Human Exposure Thresholds assuming a 60 kg human.
These determined values were 30, 9, and 1.5 mg/kg/day for Cramer Class I, II, and III, respectively.

khammond on DSKJM1Z7X2PROD with RULES

B. Toxicological Points of Departure/
Levels of Concern Once a pesticides toxicological profile is determined, EPA identifies toxicological points of departure POD
and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment.
PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which no adverse effects are observed the NOAEL and the lowest dose at which adverse effects of concern are identified the LOAEL. Uncertainty/
safety factors are used in conjunction with the POD to calculate a safe exposure levelgenerally referred to as a population-adjusted dose PAD or a reference dose RfDand a safe margin of exposure MOE. For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see https
www.epa.gov/pesticides/factsheets/
riskassess.htm.
The human exposure threshold value for threshold i.e., non-cancer risks is based upon Cramer structural class. In the case of the fragrance components listed above, all the substances included are in the Cramer Class I category, which is defined as chemicals of simple structure and efficient modes of metabolism, suggesting low oral toxicity. The corresponding TTC value for substances in the Cramer Class I
category is 30 mg/kg/day, which is based on a 5th percentile NOEL of 3 mg/kg/
day.

VerDate Sep<11>2014

16:01 Dec 21, 2021

Jkt 256001

C. Exposure Assessment 1. Dietary exposure from food and feed uses. In evaluating dietary exposure to each of the fragrance components listed in Unit II, EPA
considered exposure under the proposed tolerance exemptions at a concentration not to exceed 100 ppm for each of the fragrance components listed in Unit II. as well as any other sources of dietary exposure. EPA assessed dietary exposures from various fragrance components in food as follows:
The dietary assessment for food contact sanitizer solutions calculated the Daily Dietary Dose DDD and the Estimated Daily Intake EDI. The assessment considered: Application rates, residual solution or quantity of solution remaining on the treated surface without rinsing with potable water, surface area of the treated surface which comes into contact with food, pesticide migration fraction, and body weight. These assumptions are based on Food and Drug Administration FDA
guidelines.
The dietary assessment for food contact sanitizer solutions showed that children 1 to 2 years old would be the highest exposed subgroup 48% of the chronic PAD cPAD. The general U.S.
population resulted in 19% of the cPAD. Any percent cPAD exceeding 100% would be of concern.
2. Dietary exposure from drinking water. For the purpose of the screening level dietary risk assessment to support this request for an exemption from the requirement of a tolerance for various fragrance components a conservative drinking water concentration value of 100 ppb based on screening level modeling was used to assess the contribution to drinking water for the chronic dietary risk assessments for parent compound. These values were directly entered into the dietary exposure model.
3. From non-dietary exposure. The term residential exposure is used in this document to refer to nonoccupational, non-dietary exposure e.g., textiles clothing and diapers, carpets, swimming pools, and hard surface disinfection on walls, floors, tables.
Various fragrance components may be used as inert ingredients in products that are registered for specific uses that may result in residential exposure, such as pesticides used in and around the home. The Agency conducted a conservative assessment of potential residential exposure by assessing various fragrance components in pesticide in disinfectant-type uses
PO 00000

Frm 00021

Fmt 4700

Sfmt 4700

72527

indoor scenarios. The Agencys assessment of adult residential exposure combines high-end dermal and inhalation handler exposure from indoor hard surface, wiping and aerosol spray. The Agencys assessment of childrens residential exposure includes total post-application exposures associated with total exposures associated with contact with treated indoor surfaces dermal and hand-tomouth exposures.
4. Cumulative effects from substances with a common mechanism of toxicity.
Section 408b2Dv of FFDCA
requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider available information concerning the cumulative effects of a particular pesticides residues and other substances that have a common mechanism of toxicity. EPA has not made a common mechanism of toxicity finding as to these fragrance chemicals listed in unit II and any other substances, and these fragrance chemicals do not appear to produce toxic metabolites produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that these fragrance chemicals listed in unit II have a common mechanism of toxicity with other substances. For information regarding EPAs efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPAs website at https
www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children FFDCA Section 408b2C provides that EPA shall retain an additional tenfold 10X margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children.
This additional margin of safety is commonly referred to as the Food Quality Protection Act FQPA safety factor SF. In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor. The FQPA SF has been reduced to 1X in this risk assessment because clear NOELs and LOELs were established in the studies analyzed by Munro et al. 1996 which included developmental and reproductive toxicity studies, maternal and
E:FRFM22DER1.SGM

22DER1