UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF
CHEMICAL SAFETY ANO
POLLUTION PREVENTION

MEMORANDUM

Date : April 5, 2012

SUBJECT: Fluridone: ID # I2ARD 1 Section 18 E mergency Exemption for Use on Cotton in Arkansas, South Ca rolina, Tennessee, and Florida.

PC Codes: 112900
Decision No

. : 462422
Petition No

. : NA DP Barcode: 39989 2 Registration No.: None Regulatory Action: Section 18 Registration

Risk Assessment Type: NA

TXRNo

. :NA Case No.: NA
CAS No.: 59756·60-4
40 CFR: 180.420 MRID No.: NA

FROM:

THROUGH:

TO : Danette Drew. Chemist! Risk

## Assess**~ ~~M**  Matthew Lloyd (CIH), Industrial Hygienist

# ~ William Irwin, Ph.D., Toxicologist ) .? r-i;> Risk Assessment Branch VNII

### (j)~**~** Health E ffect s Division (7509P)

Michael S. Metzger. Branch

## Chie**/c~/Jf'j rf** **~** Risk Assessment Branch V NIl 

## M 

# lA- '

Health Effects Di v ision (7509P)

Keri Grinstead / Marcel Howard Registration Divi s ion (7505P)

Executive Summary

The Arkansas State Plant Board has requested a Section 18 Specific Exemption for the

use of fluridone on cotton in A rkansa s, South Carolina, Tennessee, and Florida. This

Page 1 of 10Page 2 of 10

Section 18 w ould allow application of fluridone, as the end

- use product Brake ® (EPA Registration No. 67690

- 54 )

, to control Palmer amaranth during the 201 2 cotton growing

season. This is the first Section 18 request for this use.

EPA’s Health Effects Division ( HED ) has examined the Section 18 request materials and
available data and has determined that the proposed use of fluridone on cotton , and on turnrows and ditchbanks adjacent to cotton fields, is supported by recent fluridone human
health risk assessments , primarily those prepared for the 2004 Tolerance Reasse ssment Progress and Risk Management Decision (TRED)

. T he dietary (food, water), residential, and aggregate risk estimates determined in the most recent risk assessments remain unchanged and are below HED’s level of concern. The occupational exposure scena rios
assessed in conjunction with this Section 18 proposed use on cotton ind icate that occupational handler exposures will not exceed HED’s level of concern with baseline clothing

. The WPS reentry interval of 12 hours listed on the original label is adequ ate for
the proposed use

.

HED concludes that t he application of Brake ® (fluridone) to control Palmer amaranth in

cotton would not result in occupational, dietary (food or water) , residential, or aggregate (dietary plus residential) exposure s or risk es timates of concern provided the Section 18 supplemental label (EPA Reg. N o. 67690

- 54) is modified to specify the maximum
seasonal rate allowed [do not apply more than 1.56 gallons of Brake per acre (0.5 pounds active ingredient fluridone/acre) per year ]

.

For the purposes of this Section 18 request only, the cited residue data may be used to conclude that the residues of fluridone on cotton would not be expected to exceed the current tolerance 0.1 ppm ( cotton

, undelinted seed) when fluridone is applied pr eplant or preemergent to cotton field soil, or to turnrows and ditchbanks adjacent to cotton fields,
at a maximum seasonal rate of 0.5 lb ai/A.

Codex maximum residue limits (MRLs), Mexican MRLs, and Canadian MRLs have not
been established for fluridone re sidues, so there are no concerns for international
harmonization with U.S. tolerances.

General Use Information

Fluridone (1

- methyl

- 3

- phenyl

- 5

- [3

- trifluoromethyl) phenyl]

- 4(1 H )

- 5

- [3

- (trifluoromet hyl)phenyl]

- 4(1 H )

- pyridinone) is an aquatic herbicide used on ponds (including a homeowner use), lakes, reservoirs, irrigation canals, drainage canals, and
rivers. Fluridone may also be used in dry canals.

The currently registered uses of fluridone may result in dietary exposures from food from irrigated crops and from drinking water. Residential uses of fluridone can result in dermal and inhalation exposure. People may also be exposed when swimming in treated water, resulting in dermal, ingestion, aural, buccal/sublingual, and nasal/orbital exposure. Occupat ional uses may result in exposures via the dermal and inhalation routes.Page 3 of 10

The proposed Section 18 use pattern is as follows:

The end

- use product, Brake ® , is a soluble concentrate containing 3.79% fluridone (0.32 lb ai/gallon). One broadcast or band ap plication at a maximum seasonal rate of 0.5 lb ai/A is proposed for cotton fields and for turnrows and ditchbanks adjacent to cotton
fields

. Brake ® may be applied as a preplant soil incorporated or preemergence surface application to cotton fields

. Appli cations to turnrows and ditchbanks should be made prior to Palmer amaranth emergence or tankmixed with an herbicide labeled for removal of existing weeds. Chemigation is prohibited. There are no aerial applications as the label directions clearly direct the user to ground

- based application equipment. The use period is from April to June 2012 for cotton fields and from March 1 to August 1, 20 12
for turnrows and ditchbanks. The exemption expiration would be August 1, 2012.

The Section 18 supplemental Bra ke ® label , EPA Reg. No. 67690

- 54, does not specify a
maximum seasonal (or annual) rate and states “do not make more than two consecutive applications” . The parent label, 67690

- 48, does specify “do not apply more than 1.56 gallons of Brake per acre (0.5 po unds fluridone/acre) per year ”. The supplemental label should specify the maximum annual rate allowed.

Hazard Identification and Toxicology

Fluridone has low to moderate acute oral, inhalation and dermal toxicity. Fluridone is

not irritating to skin, n or is it a skin sensitizer, but is a moderate irritant to the eyes. The liver and kidneys were the target organs in rats following sub

- chronic dietary exposures

. Following sub

- chronic exposure to dogs , no systemic toxicity was observed

. Fluridone
caused hepatotoxicity

, characterized as alterations in a liver enzyme and increased liver weight , in chronic dog studies

. T he target organs for fluridone

- induced toxicity were the liver, kidneys, and testes , revealed in chronic toxicity/carcinogenicity studies

. Toxicity
in mice was limited to the liver and manifested as changes in a liver enzyme and histopathology , observed in a carcinogenicity study

. Based on the lack of evidence for carcinogenicity in these studies (mice and rats), fluridone is classified as Group E Carcinogen

- Evidence of Non

- Carcin ogenicity for Humans. There is no evidence that fluridone has the potential to be toxic to either the nervous or the immune system. There is no evidence of increases susceptibility following in utero exposures to rats and rabbits or following pre

- and post

- natal exposures to rats for two generations.

Toxicological points of departure (PODs) were selected for acute and chronic oral

exposures. PODs were also selected for short

- term and intermediate

- term oral, derm al, and inhalation exposures

. The 10X FQPA Safety Factor was re duced to 1X since the toxicology data base is substantially complete, there are no residual uncertainties for pre

and/or post

- natal toxicity, and dietary and residential exposures are not like ly to be
underestimated.

The hazard identification and toxicology for fluridone is based on the recent human health risk assessment scoping document completed in 2009 (D361849). S ummar y tablesPage 4 of 10

of the most recent toxicological PODs and uncertainty factors can be found in Appendix
1.

Residue Chemistry and Tolerance

Fluridone is currently not registered for direct application to crops, but crops may be irrigated with treated water

. Tolerances are established for fish, crayfish and animal
commodities. Tole rances are also established for indirect or inadvertent residues of fluridone on several crops as a result of irrigation with treated water. The current
tolerance for residues of fluridone on cotton, undelinted seed is 0.1 ppm and is listed in
40CFR 180.4 20 (c) under the following definition:

180.420(c) Tolerances are established in the following irrigated crops and crop groupings for residues of the herbicide fluridone , including its metabolites and degradates, resulting from use of irrigation water cont aining residues of 0.15 ppm following applications on or around aquatic sites. Where tolerances are established at higher levels from other uses of fluridone on the following crops, the higher tolerance also applies to residues in the irrigated commodity. Compliance with the tolerance levels specified below is to be determined by measuring only fluridone

Codex maximum residue limits (MRLs), Mexican MRLs, and Canadian MRLs have not been established for fluridone residues, so there are no concerns for inter national
harmonization.

No residue data were submitted with this request. Several literature and unpublished study citations w ere provided by the petitioner. The conclusions of select unpublished studies were briefly summarized and indicated that residu es of fluridone on cotton would not be expected to exceed the current tolerance based on the proposed Section 18 use. HED has examined these studies and modified the petitioner conclusions as follows:

In Rainey et al. (1977), total radioactive residues (TRR), determined by liquid scintillation counter (LSC), in whole cotton plants grown in soil incorporated treatments at up to 0.75 lbs ai/A with C 14

- fluridone w ere ≤ 0.0006 ppm 60 days after treatment (CA). Additionally, at two sites (CA and MS) applic ations of up to 0.75 lbs ai/A C 14

- fluridone were made as either soil incorporated or soil surface treatments prior to planting
cotton. C ottonseed was harvested from mature cotton about five months after treatment and planting and was delinted prior to LSC analysis. At the CA site, which had a soil incorporated treatment, mean TRR in delinted cottonseed were < 0.0028 ppm (corrected for controls). At the MS site, control

- corrected TRR in delinted cottonseed were < 0.0009 ppm for soil incorporated treatment s and were ≤ 0.0012 ppm for surface

treatments.

In West and Burger (1978a), a variety of soil types in four sites (NC, MS (2), and AL)

were surface treated (band application) with one application at either 0.4 lb ai/A or 0.6 lb
ai/A fluridone. It was not clear from the study report if applications of fluridone werePage 5 of 10

made preemergent of cotton plants; however, sampling of mature cottonseed was performed approximately five months after treatment. Residues of fluridone in ginned
cottonseed were nondetectable (<0.01 ppm) from all locations.

In West and Burger (1978b), a variety of soil types in four sites (CA, MS (2), and GA)

w ere treated with fluridone as either a soil incorporated preplant application or as a surface application. Two applications were made one year apart. The annual (seasonal) application rates ranged from 0.6 lb ai/A to 1.0 ai/A of fluridone. Sampling of mature cottonseed was performed approximately five months after treatment. Residues of fluridone in ginned cottonseed were nondetectab le (<0.01 ppm) from all locations.

In Day and West (1975a)

, a variety of soil types in ten sites (AR (2), AZ (2), GA, NC (2), and TX) w ere treated with one application of fluridone as either a soil incorporated preplant application or as a surface applic ation (at planting). Application rates ranged
from 0.75 lb ai/A to 1.5 ai/A of fluridone. Sampling of cottonseed was performed four to
seven months after treatment. Residues of fluridone in cottonseed were nondetectable (<0.01 ppm) from all locations.

In the Rainey study, cottonseed was delinted ( short cotton fibers removed from the seed ) prior to analysis. Tolerances are established on the commodity cotton

, undelinted seed (short cotton fibers are not removed from the seed)

. Given the very low levels of TRR found (<0.0028 ppm) in delinted cottonseed at preplant treatments of up to 0.75 lb ai/A, parent fluridone residues would not be expected to exceed the current tolerance 0.1 ppm in undelinted cottonseed when fluridone is applied to cotton field soil ( or to turnrows and
ditch banks adjacent to cotton fields) at a maximum seasonal rate of 0.5 lb ai/A. Additionally, it is assumed that in West and Burger (1978a) and West and Burger (1978b) that the cottonseed was ginned but not delinted, i.e. the cottonse ed was
undelinted

; r esidues were nondetectable in undelinted seed with soil treatment rates up to
1.0 lb ai/A fluridone.

For the purposes of this Section 18 request only, the cited data may be used to conclude
that the residues of fluridone on cotton wou ld not be expected to exceed the current tolerance 0.1 ppm ( cotton

, undelinted seed) when fluridone is applied preplant or preemergent to cotton field soil, or to turnrows and ditchbanks adjacent to cotton fields,
at a maximum seasonal rate of 0.5 lb ai/A.

Dietary Exposure

U pdated dietary exposure assessment s are not required to support the proposed Section
18 use of fluridone on cotton. The most recent assessments ( 2004 TRED ) adequately cover dietary exposure potential from the proposed use.

Fluridone may be applied directly to water bodies to achieve a target water concentration of 10 ppb to 90 ppb for whole lake treatments and 30 to 150 ppb for partial lake

treatments. Product labels contain restrictions regarding fluridone use near potable water
int akes. Applications of greater than 20 ppb are not allowed within a quarter mile ofPage 6 of 10

intakes while applications of 6 to 20 ppb are allowed at intakes. Given this label restriction it can be assumed that the concentration of fluridone in drinking water draw n from lakes would be 20 ppb or less. A toxic environmental degradate of fluridone, N

methyl formamide (NMF), may also be found in drinking water as a result of fluridone applications. Previous d ietary risk estimates from drinking water only (including
f luridone and NMF) , based on surface water estimated concentrations of 20 ppb, were
well below the level of concern. Estimated Margins of Exposure ( MOEs ) ranged from
values in the thousands to tens of thousands (the level of concern is MOE< 100)

.

EPA’s En vironmental Fate and Effects Division (EFED) has provided a drinking water

assessment (DWA) for the proposed Section 18 fluridone use on cotton (D399893 and D400398, 4/2/12). Surface water estimated drinking water concentrations (EDWCs)
were estimated for broadcast spray on (1) cotton fields and adjacent turn rows using the FIRST model and (2) ditch banks adjacent to cotton fields using the Tier I Rice model
and a screening scenario. Ground water EDWCs were estimated using the SCI GROW
Tier 1 model. EFED c onclude d that these proposed uses result in water concentrations
lower than those previously estimated based on direct application to water bodies (maximum EDWC of 20 ppb for ground or surface water). Based on the maximum fluridone application of 0.5 lb a i/ A, the highest EDWCs were for surface water after application to cotton fields and turnrows; the estimated peak concentration for acute dietary exposure assessment is 9.6 ppm. The estimated annual average concentration for chronic assessment is 2.5 ppm.

The EDWCs provided in EFED’s current assessment are conservative estimates of concentrations in drinking water. Degradate of concern N

- methyl formamide (NMF) is not assessed separately as in the previous DWA. Instead, a total toxic residues approach
is used and the aqueous photolysis half

- life of fluridone is assumed to be stable to account for the formation of NMF as the parent compound declines. Dietary exposures to drinking water will not be greater than those assessed in 2004 and are not of risk

co ncern.

A dietary exposure assessment (using DEEM) was conducted for food only (D 299947;
2004 ) in association with the TRED

. The acute and chronic analyses were conducted using tolerance level residues and assum ed 100% crop treated (including cotton)

. Re sulting e xposure estimates for the acute and chronic analyses were <5% of the population adjusted dose (PAD) for all population subgroups assessed and are not of risk

concern

. These analyses are conservative so the actual dietary exposure is likely lo wer than the estimates provided. For example, between the years 2005 and 2009 the USDA Pesticide Data Program (PDP) analyzed more than 37,000 assorted crop samples for
fluridone

. L ow level r esidues of fluridone were detected in just four of those samples (ye ar 2009 potatoes; residues between 0.002 ppm

- 0.006 ppm). T he unrefined (tolerance level, 100% crop treated) 2004 dietary exposure assessment is adequate to cover the proposed fluridone use on cotton.

Aggregate Risk AssessmentPage 7 of 10

The aggregate risk assessm ent considers the combined risk from dietary exposure (food and water) and any non

- occupational (residential) exposures. In the 2004 TRED, the aggregate assessment considered combined exposures to fluridone from food, drinking
water, and swimming in treat ed water bodies. Aggregate assessments were also performed for the aqueous photoproduct NMF for drinking water and swimmer exposure (NMF is not found in foods). All aggregate exposures were below the level of concern (MOEs were all ≥ 1500; the level of c oncern is an MOE < 100) . Since the TRED, a new
homeowner

- use product was registered, but th at residential handler exposure has not been quantitatively assessed in an aggregate assessment with food and drinking water. However, considering the high MOEs fo r food, water, and residential handling exposures, the aggregate exposure will not result in risk estimates of concern.

The proposed Section 18 use is to cotton in agricultural settings and does not impact residential exposure. As described previously in this memorandum, t he proposed use pattern is not expected to impact dietary exposure estimates. Consequentially, the current aggregate exposure assessment for fluridone is not impacted by the Section 18 request

.

Occupational Exposure

HED conducted an occupational assessment for the proposed single maximum seasonal application rate of 0.5 lb s ai/A on cotton. Chemigation is prohibited, and the label directions clearly direct the user to ground

- based application equipment so aerial exposure scenarios were not assessed.

Occupational handlers are expected to have exposures consistent with HED’s short

- and
intermediate

- term exposure durations . L ong

- term ( more than 6 consecutive months )
handler exposures are not expected.

The following scenarios are e xpected from the proposed use on cotton :

1) Mixer/Loaders Using Open Pour loading of liquids, and 2) Applicators (applications will be made in conjunction with planting).

The Agency’s level of concern for occupational exposures and risk estimates is de fined by the uncertainty factors that are applied to the assessment. For dermal and inhalation exposures, t he total uncertainty factor that has been applied is 100 X [10X interspecies factor ( animal

- to

- human) extrapolation and 10X for intraspecies (h uman) variations]. A Margin of Exposure (MOE) greater than 100 would not exceed HED’s level of concern.

The results of the occupational handler assessment are summarized in Table 1 below. The
result ing MOEs at the baseline scenario (no gloves or respiratory pro tection) are greater than 100 and do not exceed HED’s level of concern. Baseline personal protective equipment is proposed on the Section 18 label.Page 8 of 10

Table 1. Short

- /Intermediate

- Term Occupational Exposure and Risk Estimates for Fluridone.

Exposure Scen ario Application Rate (lb ai/gallon) 2 Amount

Handled Daily (gallons) 3 Baseline Unit

Exposures (ug/lb ai) 1 Dose (mg/kg/day) MOE Total
MOE 6

Dermal Inhalation Dermal 4 Inhalation 4 Dermal 5 Inhalation 5 Dermal +
Inhalation * No Respirator * No Respirator * No Respirator
Occupational Handler Scenarios

- Cotton

Groundboom: Mixer/Loader (liquids) 0.5 200 220 0.219 0.43 0.0011 140 14,000 140

Groundboom: Applicator 0.5 200 78.6 0.34 0.15 0.0017 390 8,800 380

1. Unit Exposures are taken the U.S. Environ mental Protection Agency, Office of Pesticide Programs’ “Occupational Pesticide Handler Unit Exposure Surrogate Reference Tab le” March 2012 . Units = mg a.i./pound of active ingredient handled. Dermal unit exposure is for use of a single layer of work clo thing (long pants, long

- sleeved shirt, shoes plus socks). This personal protective equipment (PPE) is specified on the product label. 2. Applic. Rate. = Taken from Section 18 request ; listed in lbs ai/A
3. Units Treated are taken from information in E xpoSAC policy 9. 4. Average Daily Dose ; Dermal ADD incorporates 39% dermal absorption factor 5. MOE = Margin of Exposure = NOAEL ADD. NOAEL for dermal and inhalation = 15 mg/kg bw/day.

6 Total MOE = NOAEL (mg/kg/day)/Dermal Dose + Inhalation Dose

.Page 9 of 10

Because of the proposed application methodology, HED does not expect worker post

application exposure. Fluridone is classified as Toxicity Category III via the dermal route of exposure and as Toxicity Category IV for skin irritation potential. It is n ot a skin
sensitizer. Therefore, the WPS reentry interval ( REI ) of 12 hours listed on the original label is adequate for the Section 18 proposed uses.

Conclusions

HED concludes that t he application of Brake ® (fluridone) to control Palmer amaranth in

cotton would not result in occupational, dietary (food or water), residential, or aggregate (dietary plus residential) exposure s or risk estimates of concern provided t he Section 18 supplemental label is modified to specify the maximum seasonal rate allowe d [do not apply more than 1.56 gallons of Brake per acre (0.5 pounds active ingredient fluridone/acre) per year ]

.

For the purposes of this Section 18 request only, the cited residue data may be used to
conclude that the residues of fluridone on cotton w ould not be expected to exceed the current tolerance 0.1 ppm (cotton, undelinted seed) when fluridone is applied preplant or preemergent to cotton field soil, or to turnrows and ditchbanks adjacent to cotton fields,
at a maximum seasonal rate of 0.5 lb ai/ A.

Codex maximum residue limits (MRLs), Mexican MRLs, and Canadian MRLs have not been established for fluridone residues, so there are no concerns for international
harmonization.

References

Author Barcode Date Title M. Lloyd D400522 4/ 4 /12 Fluridone: Occupational Assessment to Support Registration for the Proposed Section 18 Use on Cotton.
E. Gelmann D399893,

D400398 4/2/12 Drinking Water Assessment for the Proposed Section 18 Emergency Exemption Use of Fluridone on Arkansas Cotton C. Olinger, A.
La May, B. Chin D361849 7/16/09 Fluridone. Human Health Assessment Scoping Document in Support of Registration Review A. LaMay D353630 9/19/08 Fluridone: Occupational and Residential Exposure/Risk Assessment for Proposed Use of Fluridone in a Ready

- to

- Use F ormula for
Residential Ponds.
U.S. EPA NA 9/20/04 Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment Progress and Risk Management Decision (TRED) for
Fluridone
T. Dole D306456 8/17/04 Human Health Risk Assessment for Fluridone TRED C. Olinger D299947 8/12/04 Fluridone Acute and Chronic Dietary Exposure Assessments for the Reregistration Eligibility Decision Rainey et al. NA 1977 14C Fluridone Residue Study in Cotton and Selected Rotational Crops. Unpublished Study. (petitioner citat ion) Day and West NA 1975a Residue Data on EL

- 171 for Weed C ontrol in C otton. Unpublished Study. (petitioner citation) West and Burger NA 1978a Fluridone and Trifluralin Residues in Cottonseed. Unpublished Study. (petitioner citation) West and Burger NA 1978b Fluridone Residue in Cottonseed. Unpublished Study. (petitioner citation)Page 10 of 10

Appendix 1 Summary of Toxicological Doses and Endpoints for Fluridone for Use in Dietary and Non

- occupational
Human Health Risk Assessments Exposure/
Scenario Point of Dep arture Uncertainty

Factors RfD/PAD Study and Toxicological Effects

Acute Dietary (females 13

- 49 years of age ) Dev. NOAEL

= 125 mg/kg/day UF A = 10x

UF H =10x FQPA SF =
1X Acute RfD =

1.25 mg/kg/day
Acute PAD =
1.25 mg/kg/day Developmental Toxicity

- Rabbit

LOAEL = 300 mg/kg/day based on
increased incidences of abortions

Acute Dietary (general population) NOT APPLICABLE. A dose and endpoint were not selected for this population group

because there were no effects observed in oral toxicology studies includin g maternal toxicity in the developmental toxicity studies in rats and rabbits that are attributable to a single exposure (dose).

Chronic Dietary (all populations) NOAEL = 15

mg/kg/day UF A = 10x

UF H =10x FQPA SF =
1X Chronic RfD

= 0.15mg/kg/da

y Chronic PAD
= 0.15 mg/kg/day 2 yr cancer study in mice

LOAEL =50 mg/kg/day based on increased alkaline phosphatase activity
and increased incidence of heptocellular hyperplasia

Incidental oral
Short

- and
Intermediate

- Term

exposures NOAEL = 15

mg/kg/day UF A = 10x

UF H = 10x MOE = 100 2 yr cancer study in mice (Same as above)

Cancer (oral) Fluridone is classified as “not likely” to be a human carcinogen. Quantitative cancer risk

assessment is not required. Summary of Toxicological Doses and Endpoints for Fluridone for Use in Residential and Occupational
Human Health Risk Assessments

Exposure/
Scenario Point of Departure Uncertainty

Factors Level of

Concern for
Risk
Assessment Study and Toxicological Effects
Dermal
Short

- and
Intermediate

- Term NOAEL =

15 mg/kg/day UF A = 10x

UF H =10x MOE = 100 2 yr cancer study in mice (Same as above)

Dermal Long

- Term The endpoint is not applicable because use pattern does not indicate long

- term exposure.

Inhalation Short

- and
Intermediate Term NOAEL =

15 mg/kg/day UF A = 10x

UF H =1 0x MOE = 100 2 yr cancer study in mice (Same as above)

Inhalation Long

- Term The endpoint is not applicable because use pattern does not indicate long

- term exposure.

Cancer (dermal and inhalation) Fluridone is classified as “not likely” as a human carc inogen. Quantitative cancer risk

assessment is not required. Point of Departure (P o D) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies).
UF DB =Database uncertainty factor. PAD = population adjusted dose (a = acute, c = chronic) = the NOEL/all appropriate uncertainty and safety factors. RfD = referen ce dose. MOE = margin of exposure.