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

OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION

December 3, 2015

MEMORANDUM

SUBJECT: Petition No.: IN-10777; Salicylaldehyde . Human Health Risk Assessment and Ecological Effects Assessment to S upport Proposed Exemption from the Requirement of a Tolerance When Used as an Inert Ingredient in Pesticide
Formulations.

PC Code: 730944 DP Barcode: N/A
Decision No.: N/A Regulatory Action: Inert Tolerance Exemption; 40 CFR 180.910
Petition No.: IN-10777 CAS Reg. No.: 90-02-8 Inert Tracking No.: N/A

FROM: William Cutchin, Chemist Chemistry, Inerts and Toxicology Assessment Branch (CITAB) Registration Division (RD) (7505P)

THROUGH: Kerry Leifer, Team Leader CITAB/RD (7505P)

TO: Pv Shah, Branch Chief CITAB/RD (7505P)2 

### Table of Contents

EXECUTIVE SUMMARY ............................................................................................................. ................................. 3

I. BACKGROUND

.............................................................................................................................. ...................... 5

II. INERT INGREDIENT PROFILE ...................................................................................................... ..................... 6

III. HUMAN HEALTH ASSESSMENT ....................................................................................................... ........... 6

IV. DIETARY EXPOSURE ASSESSMENT ................................................................................................... ...... 13

V. RESIDENTIAL EXPOSURE AND ASSESSMENT ........................................................................................... . 15

VI. AGGREGATE RISK AND DETERMI NATION OF SAFETY ....................................................................... 15

VII. OCCUPATIONAL EXPOSURE/RISK PATHWAY ....................................................................................... 16

VIII. CUMULATIVE EXPSOURE ........................................................................................................... ................ 28

IX. ENVIRONMENTAL JUST ICE STATEMENT ............................................................................................... 28

X. ENVIRONMENTAL FATE CONSIDERATIONS ............................................................................................. . 29

XI. ECOTOXICITY ................................................................................................................... ............................. 29

XII. RISK CHARAC TERIZATION ......................................................................................................... ................ 293 EXECUTIVE SUMMARY

Ag-Chem Consulting LLC, on behalf of Om ex Agrifluids, is proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosm etic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.910 to establish an exemption from the requirement of a tolerance for salicylaldehyde (2-hydroxybenzal dehyde; CAS Reg. No. 90-02-8 ) in or on food crops at no more than 14% of the pesticide formulation to help th e active ingredient properl y penetrate and remain
available to act in the soil.

The acute oral toxicity of salicylaldehyde was examined in female rats with 3 rats in one group, and a study was performed using the stepped method in which one-time oral administrations were performed in stages while checking the death conditions for a fixed dosage. From the above results, the general lethal amount in rat oral administrati on of salicylaldehyde is estimated to be 500mg/kg. The dermal LD 50 for salicylaldehyde was determined to be greater than 23 g/kg. Dermal irritation studies fo und salicylaldehyde to be irritating, with eschar formation and scarring 14 days after administration.

Salicylaldehyde was negative in a rat bone marrow micronucleus test and had no clastogenicity in rat bone marrow cells.

In a study in male and female rats (Crj: CD (S D) type SPF), no effect s of administration of the salicylaldehyde substance were found on the fema le estrus cycle and es trus count, on the male and female mating and impregnation, and on the fe male animal pregnancy period and parturition.
No effects of administration of salicylaldehyde were found on nursing Day 0 in the number of live birth infants, number of still borns, sex ratio, parturition rate, and birth rate. At doses below 40 mg/kg, no effects of administration of salicylalde hyde were found in general conditions, weight, feed volume, hematological test values, blood ch emistry test values, autopsy findings, and organ weight.

There are no cancer studies available for salicylaldehyde. Based on predicted rapid metabolism and excretion, lack of specific target or gan toxicity in the repeat dose studies study and lack of mutagenicity, salicylaldehyde is not expected to be carcinogenic.

The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is intended to provide an additional l0-fold safety f actor (10X), to protect for special sensitivity in infants and children. Based on available information, the FQPA safety factor should be reduced to

IX.

No acute toxicological endpoint of concer n has been identifie d for salicylaldehyde. On the basis of the Repeated Dose and Reproductive /Developmental Toxicity Screening study, a no observed adverse effect level ( NOAEL) for parental systemic t oxicity and embryo/developmental toxicity NOAEL for salicylaldehyde was 40 mg/kg bw/day. Based on the reduced FQPA Safety Factor for salicylaldehyde of IX , the chronic reference dose (cRf D) and the chronic population adjusted dose (cPAD) are 0.4 mg/kg. The chronic or al NOAEL is also applicab le to the dermal and inhalation exposure routes.4 The Agency assessed the dietary exposures to sa licylaldehyde as an iner t ingredient used in pesticide formulations applied to growing crops and livestock. No a dverse effects attributable to a single exposure to sali cylaldehyde were seen in the toxicity databases; therefore, an acute dietary risk assessment is not ap propriate. In conducting the chronic dietary exposure assessment using the Dietary Exposure Evaluation Model DEEM–FCID TM , no residue data were submitted for salicylaldehyde. In the absence of specific resi due data, EPA has developed an approach which uses surrogate information to derive upper bound exposure estimates for the subject inert ingredient. Upper bound exposure estimates are based on the highest tolerance for a given commodity from a list of high-use insecticides, he rbicides, and fungicides. In the dietary exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest tolerance for a given commodity. Im plicit in this assumption is that there would be similar rates of degradation (if any) between the active and inert ingredient and that the concentration of inert ingredient in the scenarios leading to these highest of tolerances would be no higher than the concentration of the active ingr edient. DEEM model estimates for oral exposure from the use of salicylaldehyde in pesticidal fo rmulations (including e xposure through drinking water) resulted in chronic diet ary exposure estimates for food and drinking water below the Agency’s level of concern (<100% cPAD) for the U.S. population and all population subgroups. The chronic dietary exposure fr om food and water to salicylalde hyde is 13% of the cPAD for the U.S. population and 49% of the cPAD for child ren 1-2 years old, the most highly exposed population subgroup.

The Agency has not identified any concerns for carcinogenicity relating salicylaldehyde; therefore, a cancer dietary expos ure assessment was not performed.

The term “residential exposure” is used in this document to refer to non-occupational, nondietary exposure (e.g., for lawn and garden pest cont rol, indoor pest control, termiticides, and flea and tick control on pets). While there are no current or proposed re sidential uses for salicylaldehyde, it is possible that salicylaldehyde may be used as an inert ingredient in pesticide products. In the absence of specifi c residential exposure scenarios, risk estimates for residential exposures to salicylald ehyde can be modeled based on occu pational exposure assessments for salicylaldehyde. Given the larger treatment areas and higher concentrations of salicylaldehyde used in occupational use pesticid e products than would be seen in residential uses, MOEs for residential use scenarios would exceed 1,000 or more . Since our level of concern is for MOEs of 100 or less, there are no concerns for re sidential exposures to salicylaldehyde.

There was no hazard attributable to a single expo sure seen the in the toxicity database for salicylaldehyde; therefore, an acute aggr egate risk assessment is not required.

It is possible that salicylaldehyde may be used as an inert ingredient in pesticide products even though no residential or commercial uses on lawns or ornamentals are proposed. The dietary exposures to food and drinking wate r are aggregated with residentia l uses to calculate aggregate short- or intermediate term risks. Using the expo sure assumptions described in this unit, EPA has
concluded the combined short- and intermediate-t erm food, water, and resi dential exposures result in aggregate MOEs of 430 for adults and 170 for children (1-2 years old). Because EPA's level of concern for salicylaldehyde is a MOE of 100 or below, these MOEs are not of concern.5 Occupational handler and post-applicati on exposure may occur by the dermal and inhalation routes of exposure only. RD initially assessed ha ndler exposure and risks for salicylaldehyde in pesticides at baseline personal protective e quipment (PPE; long pants, a longsleeved shirt, shoes, socks, no chemical-resistant gloves, and no respirator y protection) which the Agency considers to be the typical minimal wo rker clothing. When handl ers are wearing typical worker clothing (i.e., baseline PPE) the majority of occupational handler scenarios do not indicate risks of concern. For the occupational handler scenarios which involve the handling of large volumes of pesticides, those which EPA believes that handlers will be wearing chemical-resistant gloves, occupational handler scenarios do not in dicate risks of concern with the addition of chemical-resistant gloves to baseline PPE (i.e., baseline plus gloves). A variety of pesticide formulations may contain salicy laldehyde. PPE is usually not re quired for worker re-entry, and therefore these postapplication risk estimates ar e based on the baseline exposure scenario (i.e., typical work clothing but no glove s). Typically, the Agency charac terizes the risk estimate in relation to the restricted entry interval (REI) for a particular active ingredient. While REIs for specific products are not discusse d in this risk assessment, occupational post-application scenarios assessed generally result in margins of exposure (M OEs) that do not indicate risks of concern on Day 0 (the day of application) except for ten postapplication scenarios. These scenarios were activities involving co rn, specifically the hand-harvesting harvesting/ detassling scenario; activities involving on grape, table, specifically the harvest, pull, thin, prune, train, tie scenario and the cane turning, girdling scenario; and activ ities involving turf, specifically the transplant, weed, harvest scenario. The Agency notes that it is not expect ed to be typical agricu ltural practice to apply herbicides, insecticides or f ungicides on the same day worker s would be conducting corn hand harvesting, detassling or grape vine training activities or turf harv esting. As noted earlier in this assessment, herbicides, insectic ides and fungicides are typicall y applied relatively early in a growing season. Typically, the Agency characterizes the risk estimate in rela tion to the restricted entry interval (REI) for a particular active ingr edient. While REIs for specific products are not
discussed in this risk assessmen t, occupational post-application scenarios assessed result in MOEs
that do not indicate risks of concern on Day 0 (the day of application).

Salicylaldehyde has been test ed for ecological toxicity. This chemical is expected to be biodegradable and is not likely to bioconcentrate. Based on the studies, salicylaldehyde has the potential to affect aquatic organisms. The chemi cal is ready biodegradable and not expected to have adverse ecological effects due to dilu tion factor and biodeg radability potential

Taking into consideration all available information on salicylaldehyde, EPA concludes that there is a reasonable certainty th at no harm to any population s ubgroup will result from aggregate exposure to salicylaldehyde wh en considering occupation, di etary exposure and all other nonoccupational sources of pesticide exposure for wh ich there is reliable information. Therefore, the Agency recommends for the establishment of an exemption from tolerance for residues of salicylaldehyde when used as a pesticide inert in gredient in pesticide formulations under 40 CFR §180.910 with the limitation that the end-use concentration not to exceed 14%.

I. BACKGROUND6 Ag-Chem Consulting LLC, 122O8 Quinque La ne, Clifton VA 20124 on behalf of Omex Agrifluids, 24730 Avenue 13, Madera CA 93637 pr oposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.910 to establish an exemption from the requi rement of a toleran ce for salicylaldehyde (salicylaldehyde) (CAS Reg. No. 90-02-8 ) in or on food crops at no more than 14% of the pesticide formulation to help the active ingredient properly penetrate and remain available to act in
the soil.

II. INERT INGREDIENT PROFILE

A. .Summary of Uses

The proposed use of salicylaldehyde is as an iner t ingredient solvent in pesticide formulations which include use on crops for pre- and post-harv est to help the active ingredient properly penetrate and remain available to act in the soil.

B. Physical Chemical Properties

Some of the physical and chemical characte ristics of salicylalde hyde, along with its
structure and nomenclature , are found in Table 1.

Table 1. Physical and Chemical Properties of Salicylaldehyde

Parameter Value Source

Structure

Ag-Chem Consulting,
Ltd CAS Reg. No. 90-02-8 Molecular Weight (g/mol) 122.12

Chemical Formula C 7 H 6 O 2 CAS Chem Name salicylaldehyde IUPAC Name salicylaldehyde Common Names hydroxybenzaldehyde, salicylic aldehyde; o -hydroxybenzaldehyde Physical State colorless oily liquid

Odor bitter almond Melting Point (°C) 1 Boiling Point (°C) 197°C Density 1.167 g/mL @ 25°C Water Solubility slight Vapor Pressure (Hg at 22°C) 0.4

III. HUMAN HEALTH ASSESSMENT

A. Summary of Toxicity Data7 A.1. Acute Toxicity

Acute

The approximate acute oral LD 50 's of salicylaldehyde were 566 mg/kg/day for male rats and 504 mg/kg/day for male mice. Clinical signs of toxicity were slight to severe weakness, salivation, prostrat ion and death.

Dermal

When applied undiluted to the depilated abdom en of guinea pigs under an occlusive wrap for 24 hours, Salicylaldehyde produced str ong skin irritation. Th e acute dermal LD 50 vas greater than 20 ml/kg for the guinea pig. The highest dose tested, 20 ml/kg, produced tremors which may be an indication of percutaneous absorption. Repe ated applications (10) to the uncovered clipped backs of guinea pigs produced m oderate exacerbation of the irritative response. None of five guinea pigs tested for allergic skin re actions exhibited a positive response.

Eye

Eye irritation tests we re not done, however, based on the se vere skin reacti on, it is assumed that this compound would produ ce severe eye irritation.

Metabolism

A single dose of 400 mg salicy laldehyde /kg bw was administ ered to a fasted rabbit. Approximately 75% of the dose was excreted in the urine collected over 24 hr. Urine analysis revealed mainly ether soluble acids, with 27% an d 3% accounted for as glucuronic acid and sulfate conjugates of vanillic acid, respectively.

A.2. Combined Repeated Dose Toxicity Study with the Reproductive/Developmental Toxicity Screening Test

To perform the repeated dose toxicity and reproductive developmental toxicity combined test based on oral administration using salicylald ehyde rats (Crj: CD (SD) type SPF), we used dosages of 0 (contrast group), 2.5, 10, 40, and 160 mg/ kg/day to discover the general toxicological effects in male and female animals due to repeated doses, and also to discover the effects on gonadal performance, mating behavior, impregna tion, and parturition and other reproductive development.

Repeated Dose Toxicity

No effects of administration of the tested s ubstance to male rats were found in general conditions, weight, feed volume, hematological test values, blood chemistry test values, autopsy findings, and organ weight. In the tested substance administration groups of 40 mg/kg/day or more, the degree of lobular peripheral adiposity in the liver and the frequency of appearance was less than in the contrast group. This is no t considered to be an adverse effect.8 In the test on female rats, aside from one mother in the 40 mg/ kg/day administration group that was partway through partur ition on pregnancy Day 22, and one mother in the 160 mg/kg/day administration group that died on pregnancy Day 22, no changes were observed in the general condition. In the 160 mg/kg administration group, the liver weight showed a high value, and the ovaries a low value. However, no effects of admi nistration of the tested substance were found in weight, feed volume, and autopsy findings. In th e tested substance administration groups of 40 mg/kg/day or more, a slight increase in the glyc ogen volume was observed inside liver cells.

From the above, we concluded that general toxicological effects unde r the test conditions
showed no adverse effects in both ma les and females at 40 mg/kg/day.

Reproductive Developmental Toxicity

No effects of administration of salicylalde hyde were found on the female estrus cycle and estrus count, on the male and female mating and impregnation, and on the female animal pregnancy period and parturition. No nursing abno rmalities were found in the tested substance administration groups of 40 mg/kg or less. Neve rtheless, in the 160 mg/kg administration group,
two cases of maternal animals we re found in which all infants had died by Day 4 of nursing. No
effects of administration of the tested substance were found in th e number of live birth females, delivery rate, luteal number, number of im plantation scars, and implantation rate.

No effects of administration of the tested substance were found on nursing Day 0 in the number of live birth infants, number of stillborns, sex ratio, parturition rate, and birth rate. No
outward abnormalities were found that could be cons idered to be traced to the tested substance
administration in newborn infants and stillborns. A large trend toward infant deaths during the nursing period was seen in the 160 mg/kg/day admi nistration group, and ther e was a low trend for newborn infant live birth rates on Day 4 of nursi ng in this same group. In addition, the weights on nursing Day 0 and Day 4 showed a trend toward a slightly low value in the 160 mg/kg/day administration group.

From the above, we concluded that reproducti ve developmental toxicological effects under
the test conditions showed no e ffects for males at 160 mg/kg/day, for females at 40 mg/kg/day, and for newborn infants at 40 mg/kg/day.

A.3. Genotoxicity

Micronucleus Test

Male and female rats [Crl:CD(SD), 7 weeks at time of administration, were used to study the presence or abse nce of salicylaldehyde micronucleus inducement in rat bone marrow cells. In five animals per one group, the tested substance wa s forcibly orally administered to males at 50, 100, 200, and 400 mg/kg, and to females at 25, 5 0, 100, and 200 mg/kg, on two times with an interval of 24 hours. The negative contrast subs tance (Japanese Pharmacopoe ia olive oil) and the positive contrast substance (cyclophosphamide monohydrate, CP) were also administered with the
same method. Since no death cases were found in any of the administration groups, we looked for9 the appearance frequency of PCE (MNPCE) with micronucleus, for all animals in the negative contrast group, the tested substance admini stration groups of 100, 200, and 400 mg/kg/day groups (male), and of 50, 100, and 200 mg/kg/day groups (f emale), and the positive contrast group. As a result, for both males and females, in the tested substance groups no signif icant increase in the MNPCE count was seen in any of the groups in comparison with the negative contrast group.

The average value of the MNPCE appearance frequency and PCE ratio in the negative contrast group was in every case wi thin the range of the test fac ility background valu es, and in the negative contrast group a significantly clear micr onucleus inducement was seen. Therefore, we
concluded that this test was suitably implemented.

From the above results, salicylaldehyde had micronucleus test negativity; it has no clastogenicity in rat bone marrow cells.

Chromosome Aberration

The salicylaldehyde in vitr o chromosome aberration inducem ent was studied using Chinese hamster cultured cells (CHL/IU), and a positive re sult was obtained. The pr oliferation suppression concentration exceeding 50% for salicylald ehyde CHL/IU cells was 0.020 mg/mL in the continuous process (48 hours), and in the short-time process (6 hours) under S9 mix existence and non-existence, 0.20 mg/mL for both. As a result, the concentrations of 0.020 mg/mL for the continuous process, and 0.20 mg/mL/ for the short- time process, were set as the maximum process
concentration for this test. One-half and one-f ourth concentrations of the maximum process
concentration were set as the medium concentr ation and low concentra tion, respectively. In the continuous process group, specimens after 24-hour and 48-hour processing were manufactured under S9 mix non-existence, and chromosome analys is performed. In the short-time process group, 6-hour processing was performed under S9 mix existence and non-existence, followed by 18 hours culturing in a fresh culturing solution to manufact ure a specimen, and chromosome analysis was performed.

As a result of 24-hour and 48-hour conti nuous processing, the CHL/IU cells showed a significant increase of cells having chromosome structural aberrations, in the 24-hour process high-concentration group (0.020 mg/mL), and signifi cance was obtained in the trend test as well. In addition, in the 48-hour pro cess high-concentration group (0.020 mg /mL/), a significant increase of cultured cells was seen, and a significant diffe rence in the trend test was obtained as well. Meanwhile, the groups with 6-hour processing u nder S9 mix existence and non-existence were both dependent on the concentration, with a significant increase in ce lls with structural aberrations. In addition, the group under S9 mix existence was dependent on the concentration, with a significant increase in polyploidy cells.

Reverse Mutation

A reverse mutation test using bacteria was used to investigate the pr esence or absence of salicylaldehyde mutagenicity, and this test obtained a negative resu lt. For the assay bacteria, five
bacterial strains we re used, including Salmonella typhimurium TA100, TA1535, TA98, TA1537,
and Escherichia coli WP2 uvr A, and a dosage setting test was performed for this test using the plate method with S9 mix no-additive and additi ve conditions. When the dosage setting test was10 performed at a dosage of 50 to 5000 ug/plate, in the S9 mix no-additive, antibiotic action was found at dosages of 1500 ug/plate or more (TA 100 at 500 ug/plate or more, and WP2 uvr A at 5000 ug/plate or more), while in the S9 mix addi tive, it was found at 150 0 ug/plate or more (TA 100 at 500 ug/plate or more). In this test, the S9 mix no-additive test was set at dosages in a range of 31.3 to 1000 ug/plate (TA100 at 15.6 to 500 ug/plate, and WP2 uvr A at 125 to 4000 ug/plate),
and the S9 mix additive test was set at 62.5 to 2000 ug/plate (TA 100 at 15.6 to 500 ug/plate, and
WP2 uvr A at 125 to 4000 ug/plate), and the test was implemented.

As a result, in both of the two rounds of te sts, since no increase wa s found in the revertant colony numbers that were more than double the solv ent contrast value in a ll dosages of the five types of assay strain used, we concluded that salicylaldehyde does not have any mutagenicity (negative) in the test system used.

B. Chronic Toxicity

To perform the repeated dose toxicity and reproductive developmental toxicity combined test based on oral administration using salicylalde hyde rats, we used dosages of 0 (contrast group), 2.5, 10, 40, and 160 mg/kg/day to discover the general toxicological effects in male and female animals due to repeated doses, and also to di scover the effects on gonadal performance, mating behavior, impregnation, a nd parturition and other reproductive development.

B. 1. Repeated Dose Toxicity

In the repeated dose toxicity study, no effects of administration of the tested substance were found in general conditions, weight, feed volume, hematological test values, blood chemistry test values, autopsy findings, and or gan weight were found on males. In the tested substance administration groups of 40 mg/kg or more, the degr ee of lobular peripheral adiposity in the liver and the frequency of appearance was less than in the contrast group in males.

The effects on females were aside from one mother in the 40 mg/kg administration group that was partway through part urition on pregnancy Day 22, and one mother in the 160 mg/kg administration group that died on pregnancy Day 22, no changes were observed in the general condition. In the 160 mg/kg administration female group, the liver weight showed a high value, and the ovaries a low value. However, no effects of administration of the tested substance were found in weight, feed volume, and autopsy findi ngs in females. In the tested substance administration female groups of 40 mg/kg or more , a slight increase in the glycogen volume was
observed inside liver cells.

From the above, the general toxicological effects under the test conditions showed no
adverse effects in both males and females at 40 mg/kg/day.

B. 2. Reproductive Developmental Toxicity

No effects on reproductive developmental toxicity in parent animals of the tested substance were found on the female estrus cycle and estr us count, on the male and female mating and impregnation, and on the female animal pre gnancy period and parturition. No nursing11 abnormalities were found in the tested substan ce administration groups of 40 mg/kg or less. Nevertheless, in the 160 mg/kg administration gr oup, two cases of mother animals were found in which all infants had died by Day 4 of nursing. No e ffects of administration of the tested substance
were found in the number of live birth female s, delivery rate, luteal number, number of implantation scars, and implantation rate.

No effects of administration of the tested substance were found on nursing Day 0 in the number of live birth infants, number of stillborns, sex ratio, parturition rate, and birth rate. No
outward abnormalities were found that could be cons idered to be traced to the tested substance
administration in newborn infants and stillborns. A large trend toward infant deaths during the nursing period was seen in the 160 mg/kg admini stration group, and there was a low trend for newborn infant live birth rates on Day 4 of nursi ng in this same group. In addition, the weights on nursing Day 0 and Day 4 showed a trend towa rd a slightly low value in the 160 mg/kg administration group.

From the above, we concluded that reproducti ve developmental toxicological effects under
the test conditions showed no e ffects for males at 160 mg/kg/day, for females at 40 mg/kg/day, and for newborn infants at 40 mg/kg/day.

C. Carcinogenicity

There are no cancer studies av ailable for salicylaldehyde. Sali cylaldehyde is metabolized mainly to ether soluble acids, with 27% and 3% accounted for as gluc uronic acid and sulfate conjugates of vanillic acid, respectively. These metabolites are generally recognized as safe: glucuronic acid is a precursor of ascorbic acid (Vitamin C) and vanillic acid is a common food additive. Based on predicted rapid metabolism and ex cretion, lack of specific target organ toxicity in the repeat dose studies study a nd lack of mutagenici ty, salicylaldehyde is not expected to be carcinogenic.

D. Special Considerations for Infants and Children

The FQPA Safety Factor (as required by th e Food Quality Protection Act of 1996) is intended to provide an additional l0-fold safety f actor (10X), to protect for special sensitivity in
infants and children. Based on available informa tion discussed thus far and below in Special Consideration for Infants and Children, the FQPA safety factor shoul d be reduced to IX.

Completeness of the Toxicological Database

A mammalian toxicology databa se that includes acute toxi city, subchronic toxicity, reproductive toxicity, developmental toxicity and genot oxicity data is availabl e and is adequate for characterizing the toxicity of salicylaldehyde an d for the quantification of hazard for dietary exposure assessment. No immunotoxi cological or neurotoxicological findings were reported in the
database. There are no residual uncertainties for pre- and/or post-natal toxicity.

Evidence of Neurotoxicity12 There is no evidence of neurotox icity in the toxicological data base for salicylaldehyde. In the repeat dose study, no clinical effects indicative of neurotoxicity were reported, no adverse findings were reported from the acute oral, dermal and ocular assessments conducted in the study, and no neuropathological findings were reported in the study.

Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

No effects on reproductive developmen tal toxicity in parent animals of salicylaldehydewere found on the fema le estrus cycle and estrus c ount, on the male and female mating and impregnation, and on the female anim al pregnancy period and parturition. No nursing
abnormalities were found in the tested substan ce administration groups of 40 mg/kg or less. Nevertheless, in the 160 mg/kg administration gr oup, two cases of maternal animals were found in which all infants had died by Day 4 of nursing. No e ffects of administration of the tested substance
were found in the number of live birth female s, delivery rate, luteal number, number of implantation scars, and implantation rate.

No effects of administration of the tested substance were found on nursing Day 0 in the number of live birth infants, number of stillborns, sex ratio, parturition rate, and birth rate. No
outward abnormalities were found that could be cons idered to be traced to the tested substance
administration in newborn infants and stillborns. A large trend toward infant deaths during the nursing period was seen in the 160 mg/kg admini stration group, and there was a low trend for newborn infant live birth rates on Day 4 of nursi ng in this same group. In addition, the weights on nursing Day 0 and Day 4 showed a trend towa rd a slightly low value in the 160 mg/kg administration group.

From the above, we concluded that reproducti ve developmental toxicological effects under
the test conditions showed no e ffects for males at 160 mg/kg/day, for females at 40 mg/kg/day, and for newborn infants at 40 mg/kg/day.

Considering the overall toxicity profile and the endpoints and doses selected for salicylaldehyde, the degree of concern for the eff ects observed in the salicylaldehyde reproductive and developmental toxicity scr eening study is low; no ting that there is a clear NOAEL for the offspring effects and regulatory doses were select ed to be protective of these effects. No other residual uncertainties were identified with resp ect to susceptibility. Th e endpoints and doses selected for the dietary risk assessment of salicyl aldehyde are protective of adverse effects in both offspring and adults.

Residual Uncertainty in the Exposure Database

The dietary risk assessment for salicylald ehyde is based on conservative, high-end assumptions and as such the exposure assessment is not likely to underest imate actual exposures

Since there is an adequate repeat dose st udy at doses up to 160 mg/kg/day, the FQPA Safety Factor (SF) has been reduced to 1X. The acute and chronic popul ation-adjusted doses (aPAD and cPAD) would be equal to the acute and chronic Rf Ds, respectively.13 E. Toxicity Endpoint Selection

No acute toxicological endpoint of concer n has been identified for salicylaldehyde.

On the basis of the Repeated Dose and Re productive/Developmental Toxicity Screening study, a NOAEL for parental systemic toxicity and embryo/developmental toxicity NOAEL for salicylaldehyde was 40 mg/kg bw/day. As summ arized above, the available toxicology data support that the FQPA safety factor for salicy laldehyde should be reduced from 10X to IX. Therefore, only the 10X factors for intra- and inter- species variability should be included in calculating the chronic reference dose (cRfD) a nd the chronic population adjusted dose (cPAD). The chronic reference dose (cRfD) is th erefore 0.4 mg/kg (40 mg/kg bw/day /100).

The chronic NOAEL is also applicable to th e dermal and inhalation exposure routes.

IV. DIETARY EXPOSURE ASSESSMENT

In conducting the chronic dietary exposure assessme nt using the Dietary Exposure
Evaluation Model DEEM–FCID TM , Version 3.18, EPA used food consumption information from the U.S. Department of Agriculture’s (U SDA’s) 2003-2008 National Health and Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in food, no residue data were submitted for salicylaldehyde. In the absence of specific residue data, EPA has developed an approach which uses surroga te information to derive upper bound exposure estimates for the subject inert ingredient. Uppe r bound exposure estimates are based on the highest tolerance for a given commodity from a list of hi gh-use insecticides, herbic ides, and fungicides. A complete description of the general approach taken to assess inert ingredient risks in the absence of
residue data is contained in the memorandum entit led “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.

In the dietary exposure assessment, the Agency assumed that the residue level of the inert ingredient would be no higher than the highest to lerance for a given commodity. Implicit in this assumption is that there would be similar rates of degradation (if any) be tween the active and inert ingredient and that the concentration of inert ingred ient in the scenarios lead ing to these highest of tolerances would be no higher than the c oncentration of the active ingredient.

The Agency believes the assumptions used to estimate dietary e xposures lead to an extremely conservative assessment of dietary risk due to a seri es of compounded conservatisms. First, assuming that the level of residue for an iner t ingredient is equal to the level of residue for the active ingredient will overstate exposure. The c oncentration of active ingredient in agricultural products is generally at least 50 percent of the product and often can be much higher. Further, pesticide products rarely have a single inert ingred ient; rather there is ge nerally a combination of different inert ingredients used which additionally reduces the concentration of any single inert ingredient in the pe sticide product in rela tion to that of the active ingredient.14 Second, the conservatism of this methodology is compounded by EPA’s decision to assume that, for each commodity, the active ingredient which will serve as a guide to the potential level of inert ingredient residues is the act ive ingredient with th e highest tolerance level. This assumption
overstates residue values becau se it would be highly unlikely, given the high number of inert ingredients, that a single inert ingr edient or class of ingredients woul d be present at the level of the active ingredient in the highe st tolerance for every commodi ty. Finally, a third compounding conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest tolerance level. In other words, EPA assumed 100 percent of all foods are treated with the inert ingredient at the rate and manner necessary to pr oduce the highest residue legally possible for an active ingredient. In summary, EPA chose a very conservative method for estimating what level of inert residue could be on food, then used this methodology to choose the highest possible residue
that could be found on food and assumed that all f ood contained this residue. No consideration was given to potential degradation between harves t and consumption even though monitoring data shows that tolerance level residues are typically one to two orders of magnitude higher than actual
residues in food when dist ributed in commerce.

Accordingly, although sufficient information to quantify actual residue levels in food and drinking water is not available, the compounding of these conservati ve assumptions will lead to a significant exaggeration of act ual exposures. EPA does not believe that this approach underestimates exposure in the absence of residue data.

A. Acute Dietary Exposure and Risk

No adverse effects attributab le to a single exposure to sali cylaldehyde were seen in the toxicity databases; therefor e, an acute dietary risk a ssessment is not a concern.

B. Chronic Dietary Exposure and Risk

A chronic dietary risk assessment takes in to account exposure estimates from chronic dietary consumption of food and dr inking water. Model estimates for oral exposure from the use of salicylaldehyde in pesticidal fo rmulations (including exposure th rough drinking water) resulted in chronic dietary exposure estimates for food and drinking water below the Agency’s level of concern (<100% cPAD) for the U.S. population a nd all population subgroups. The chronic dietary exposure from food and water to salicylaldehyde is 13% of the cPAD for the U.S. population and also 49% of the cPAD for children 1-2 years old, the most highly e xposed population subgroup.

C. Cancer Dietary Exposure and Risk

The Agency has not identified any concerns fo r carcinogenicity relating to salicylaldehyde; therefore, a cancer dietary exposur e assessment was not performed.

Table 4. Dietary Exposure Assessment for Salicylaldehyde
Population Subgroup Acute Exposure Chronic Exposure

Dietary Exposure
from DEEM Total

mg/kg/day %aPAD mg/kg/day %cPAD US Pop. NA 0.053016 1315 All Infants (<1yr) 0.110440 28 Children 1-2yr 0.197747 49 Children 3-5yr 0.135978 34 Children 6-12yr 0.070155 18 Youth 13-19yr 0.037743 9.4 Adult 20-49yr 0.040527 10 Adult 50-99yr 0.042501 11 Female 13-49yr 0.040973 10

V. RESIDENTIAL EXPOSURE AND ASSESSMENT

The term “residential exposure” is used in this document to refer to non-occupational, nondietary exposure (e.g., for lawn and garden pest cont rol, indoor pest control, termiticides, and flea and tick control on pets). While there are no current or proposed re sidential uses for salicylaldehyde, it is possible that salicylaldehyde may be used as an inert ingredient in pesticide products for which short-term and intermediate-t erm residential exposures may result. In the absence of specific residential e xposure scenarios, risk estimates for residential exposures to salicylaldehyde can be modeled based on occupati onal exposure assessments for salicylaldehyde. Occupational exposure assessments for salicylald ehyde for occupational mixer/loader/applicator exposure and occupational post-application expo sure for comparable use scenarios (e.g., low pressure handwand turf application) with only ba seline personal protective equipment result in MOEs of 500 or greater (i.e., e xposures are not of concern). Give n the larger treatment areas and higher concentrations of salicyla ldehyde used in these occupationa l use pesticide products than would be seen in residential uses, MOEs for re sidential use scenarios would exceed 1,000 or more.
Since our level of concern is for MOEs of 100 or less, there are no c oncerns for residential exposures to salicylaldehyde.

VI. AGGREGATE RISK AND DE TERMINATION OF SAFETY

A. Acute Risk

There was no hazard attributable to a single expo sure seen the in the toxicity database for salicylaldehyde; therefore, an acute aggr egate risk assessment is not required.

B. Chronic Risk.

Using the exposure assumptions described in Section III for chronic dietary exposure, EPA has concluded that chronic expos ure to salicylaldehyde from f ood and water is conservatively
estimated to utilize 49 % of the cPAD for children 1-2 yrs old, the population group receiving the greatest exposure. Chronic residential exposure to residues of salicyla ldehyde not expected.

C. Short- and Intermediate-term Risk

Short- and intermediate term aggregate exposur e takes into account s hort-term residential exposure plus chronic exposure through food and drinking water (c onsidered to be a background16 exposure level). Since it is possible that salicylal dehyde may be used as an inert ingredient in pesticide products for which short-term and interm ediate-term residential exposures may result, the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to salicylaldehyde.

Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposure s result in aggregate MOEs of 430 for adults and 170 for children (1-2 years old). Because EPA's level of concern for salicylaldehyde is a MOE of 100 or be low, these MOEs are not of concern.

Table 5. Short- and Intermediate-Term Exposure Assessment for Salicylaldehyde
Population Subgroup Chronic Dietary Exposure
from DEEM (mg/kg/day) Total Dietary
MOE 1 Residental Uses
MOE Total MOE 2

US Pop. 0.053016 750 1000 430 Children 1-2yr 0.197747 200 1000 170

1 MOE = POD (NOAEL of 40 mg/kg/day)/ (Dietary mg/kg/day)

2 Total MOE = 1/ (1/Dietary MOE + 1/Residential MOE)

D. Cancer Risk

.

The Agency has not identified any concerns for carcinogenicity for salicylaldehyde; therefore, an aggregate cancer expo sure assessment was not performed.

VII. OCCUPATIONAL EXPOSURE/RISK PATHWAY

EPA has determined that exposure to handler s as the result of us ing pesticide products which might potentially contain sa licylaldehyde as an inert ingred ient may occur in a variety of occupational environments. The representative occ upational scenarios select ed by the Agency for assessment were evaluated based on likely maxi mum application rates for products which may contain salicylaldehyde as an in ert ingredient for the short-term exposure assessment, and average application rates for products li kely to contain salicylaldehyde as an inert ingredient for the intermediate- and long-term exposur e durations. Active ingredient ap plication rates were corrected
for the maximum amount of the inert ingredient likely to be in the final formulations to determine exposure and risk from exposure salicylaldehyde . A summary of the occupational assessment is presented below.

A. Handler Risk

Exposure Scenarios17 Exposure to pesticide handlers is likely duri ng the occupational use of pesticides containing salicylaldehyde as an inert ingredient. Dermal and inhala tion exposure was estimated using the Pesticide Handlers Exposure Database (PHED) and Outdoor Residential Exposure Task Force (ORETF) data. The quantitative e xposure/risk assessment develope d for occupational handlers to support the requested tolerance exem ption for salicylaldehyde is ba sed on the following scenarios.
RD notes that these scenarios were selected to represent the scenarios wi th the highest potential

exposure.

Mixer/Loader/Applicators: 1) Mixer/Loader for aerial application- high acreage field crops (liquids) 2) Mixer/Loader for airblast application- tree nuts crops (both liquid and wettable powder) 3) Mixer/Loader for groundboom application- hi gh acreage field crops and turf (liquids and wettable powder) 4) Applicators for aerial application- high acreage field crops (liquid) 5) Applicators for airblast- tree nut crops 6) Applicators for groundboom- high ac reage field crops and turf 7) Mixer/Loader/Applicator- low pressure ha ndwand (liquids and wettable powders)* 8) High pressure handwand- gr eenhouse (wettable powders) 9) Flagging- high acreage fi eld crops (liquids) * Uses ORETF unit exposure data . All others use PHED data.

Risk estimates were calculated using the Marg in of Exposure (MOE) wh ich is a ratio of the toxicological POD to the daily dos e. Daily dose values are calculat ed by first calculating exposures by considering application parameters (i.e., rate and area treated) along with unit exposures. Exposures are then normalized by body weight to calculate dose levels. Dermal and inhalation short-term exposure is compared to the dermal and inhalation POD of 40 mg/kg/day. Dermal and inhalation intermediate-term exposure is compared to the intermediate term dermal and inhalation POD of 40 mg/kg/day. For the scen arios where applicable, dermal and inhalation intermediateterm exposure is compared to the long-term de rmal and inhalation POD of 40 mg/kg/day. For both
short- and intermediate-term dermal assessm ents, 100% dermal absorption was assumed and exposures were compared to the POD from an oral toxicity study. For both short- and intermediate-term inhalation assessments, inhalation t oxicity was assumed to be equivalent to oral toxicity. A combined dermal a nd inhalation MOE was also calculated for each exposure duration for salicylaldehyde as common toxicity endpoints we re utilized for both th e dermal and inhalation routes of exposure. To assess hand ler risks, the Agency used surr ogate unit exposure data from the PHED, and ORETF data.

Occupational handler exposure assessments ar e completed by the Agency using different levels of personal protection. The Agency typically evaluates all exposures w ith a tiered approach. The lowest tier is represented by the baseline exposure scenario followed by increasing the levels of personal protection represente d by personal protective equipment or PPE (e.g., gloves, extra clothing, and respirators) and engi neering controls (e.g., closed cab s and closed loading systems). This approach is always used by the Agency in or der to be able to define label language using a risk-based approach and not based on generic requirements for label la nguage. In addition, the minimal level of adequate protection for a chemical is generally considered by the Agency to be18 the most practical option for risk reduction. The le vels of protection that form the basis for the
calculations in this assessment include:

 Baseline Exposure Scenario: Represents typical work clot hing; a long-sleeved shirt, long pants, socks, and shoes. Chemical-resistant gloves or respiratory protection are not
included in this scenario.

 Baseline Plus Gloves: Represents the baseline exposure sc enario with the use of chemicalresistant gloves. No respiratory prot ection is included in this scenario.

 Engineering Controls: Represents the use of an appropr iate engineering control such as a closed cockpit. Engineering controls are not applicable to handheld application methods
which have no known devices that can be used to routinely lower the exposures for these
methods.

The following assumptions and factors were us ed in order to complete the exposure and risk assessment for occupati onal handlers/applicators:

 All worker scenarios were assumed to be short- and intermediate-term in exposure durations (i.e., 1-30 days and 1-6 months ) with the exception of greenhouse/hothouse applications.

 For scenarios where greenhouse/ hothouse applications are pos sible, a long-term exposure duration (6+ months) has also been calculated.

 The exposure assessment assumes an 8 hour work day.

 The maximum application rate per pesticide gr oup (herbicide/pestici de/fungicide) has been
assessed for the short-te rm exposure duration.

 The average application rate per pesticide group (herbicide/pesticide/fungicide) has been assessed for the intermediate-term exposure duration.

 A body weight of 80 kg was assumed because th e relevant toxicological PODs were not gender specific (HED HotSheet #31, 1/17/12).

 All exposures were assessed at th e baseline exposure scenario.

 For high acreage crops (e.g. corn, soybeans) where applicators can mix/load large quantities of pesticide, exposure assessments have also been completed for the baseline exposure scenario plus chemical-resistant gloves (described in the prev ious paragraph), and no respiratory protection.

Risk Characterization:

RD initially assessed handler exposure and risks for salicylaldehyde in pesticides at baseline PPE (long pants, a long-sleeved shirt, s hoes, socks, no chemical-resistant gloves, and no respiratory protection) which the Agency consid ers to be the typical minimal worker clothing.
When these assessments indicated that there were potential risks of concern for scenarios where workers would be handling larg e quantities of pesticide for high volume operations typically involving aerial applications to high acreage crops, RD repeated the assessments and included additional PPE (i.e., chemical-resistant gloves fo r pesticide handlers). The Agency believes workers handling large volumes of pesticides will be wearing chemical-resistant gloves.19 When handlers are wearing typical worker cl othing (i.e., baseline PPE) the majority of occupational handler scenarios do not indicate ri sks of concern. However, for those handler scenarios which do indicate risks of concern, wh ich involve the handling of large volumes of pesticides, EPA believes that handlers will be wearing chemical-resistant gloves and other protective equipment. Therefore, occupational handler scenarios do not indicate risks of concern with the addition of chemical-resistant gloves to baseline PPE (i.e., base line plus gloves).

Table 6. Exposure and Risks for Occupational Handlers of Salicylaldehyde in Pesticide Products (All Exposure Durations) at Baseline Exposure Scenario

Exposure Scenario

(Formulation/ Application/ Crop) Application

Rate 1 (lb inert/ A) Area
Treated Daily 2 (acres) Dermal
Unit Exposure

(mg/lb inert) 3 Inhalation
Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline
Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal
MOE 6 Baseline
Inhalation

MOE 7 Total MOE 8

Mixer/Loader Scenarios

Liquids/ Aerial Application/ High Acreage Crops (ST) 1.456

1200

2.9 1.2 72 0.029952 >1 1300 >1

Liquids/ Aerial Application/ High Acreage Crops (IT) 0.28 14 0.00576 36 87000 36

Liquids/ Airblast/ Nut Tree (ST) 1.008 40 1.7 0.0006912 300 720000 300

Liquids/ Airblast/ Nut Tree (IT) 0.448 0.7 0.0003072 670 1600000 670

Liquids/ Groundboom/ High Acreage Crops (ST) 1.456
200 12 0.004992 41 100000 41

Liquids/ Groundboom/ High Acreage Crops (IT) 0.28 2.3 0.00096 220 520000 220

Liquids/ Groundboom/ Turf (ST) 1.456 40 2.4 0.0009984 210 500000 210

Liquids/ Groundboom/ Turf (IT) 0.28 0.46 0.000192 1100 2600000 1100

Liquids/ Low Pressure Handwand/ Turf (ST) 1.008 5 0.21 0.0000864 2400 5800000 2400

Liquids/ Low Pressure Handwand/ Turf (IT) 1.008 0.21 0.0000864 2400 5800000 2400

Wettable Powder/ Airblast/ Nut Tree (ST) 0.224
40

3.7 43 0.4736 0.005504 84 7300 83

Wettable Powder/ Airblast/ Nut Tree (IT) 0.224 0.4736 0.005504 84 7300 83

Wettable Powder/ Groundboom/ High Acreage Crops (ST) 0.224

200 2.368 0.02752 17 1500 17

Wettable Powder/ Groundboom/ High Acreage Crops (IT) 0.14 1.48 0.0172 27 2300 27

Wettable Powder/ Groundboom/ Turf (ST) 0.224
40 0.4736 0.005504 84 7300 83

Wettable Powder/
Groundboom/ Turf (IT) 0.14 0.296 0.00344 135 12000 130

Wettable powder/ Low
Pressure Handwand/ Turf (ST) 1.008

5 0.2664 0.003096 150 13000 150

Wettable powder/ Low
Pressure Handwand/ Turf (IT) 1.008 0.2664 0.003096 150 13000 150

Applicator Scenarios

Liquid/ Aerial Application/ High Acreage Crops (ST) 9 1.456

1200 Eng
control only:
0.0055 Eng
control only:
0.068 0.13728 0.001697 290 24000 290

Liquid/ Aerial Application/ High Acreage Crops (IT) 9 0.28 0.0264 0.000326 1500 120000 1500

Airblast/ Nut Tree (ST) 0.224 40 0.36 4.5 0.04608 0.000576 870 69000 86020 Table 6. Exposure and Risks for Occupational Handlers of Salicylaldehyde in Pesticide Products (All Exposure Durations) at Baseline Exposure Scenario

Exposure Scenario

(Formulation/ Application/ Crop) Application

Rate 1 (lb inert/ A) Area
Treated Daily 2 (acres) Dermal
Unit Exposure

(mg/lb inert) 3 Inhalation
Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline
Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal
MOE 6 Baseline
Inhalation

MOE 7 Total MOE 8

Airblast/ Nut Tree (IT) 0.224 0.04608 0.000576 870 69000 860

Groundboom/ High Acreage Crops (ST) 1.456 200

0.014 0.74 0.05824 0.003078 690 13000 650

Groundboom/ High Acreage Crops (IT) 0.28 0.0112 0.000592 3600 68000 3400

Groundboom/ Turf (ST) 1.456 40 0.011648 0.000615 3400 65000 3300

Groundboom/ Turf (IT) 0.28 0.00224 0.000118 18000 340000 17000 Mixer/Loader/Applicator Scenarios

Low Pressure Handwand/ Turf (ORETF data) (ST) 10 1.008 5 no data 6.6 NA 0.000475 NA 84000 NA

Low Pressure Handwand/ Turf (ORETF data) (IT) 10 1.008 NA 0.000475 NA 84000 NA
Flagger Scenarios

Liquid/ Flagger/ High Acreage Crops (ST) 1.456 1200 0.011 0.35 0.27456 0.008736 150 4600 140

Liquid/ Flagger/ High Acreage Crops (IT) 0.28 0.0528 0.00168 760 24000 730

1 Application rates are based on maximum application rates of products containing inerts multiplied by 14% to convert to applicat ion rate of just inert. Applicatio n rates for Short-term (ST) expos ure risk estimates are based on ma ximum application rates. Appli cation rates for Intermediate-term (IT) and long-term (LT) exposures are based on averag e application rates. Ba seline Exposure Scenari o represents typical work clothing, no gloves.

2 Area treated daily values are from the EPA HED estimates of acreage treat ed in a single day for each exposure scenario of conce rn.

3 Unit Exposure values are reported in PHED Surrogate Expos ure Guide dated August 1998 or from ORETF data. All exposure scenarios assess baseline exposure scenario and baseline inhalatio n exposure except for aerial applicator scenarios, which asse ss inhalation and dermal exposures with engineering controls.

4 Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb inert /A) * Area Treated (A /day))/ Body Weight (70 kg) * Dermal Absorption Factor of 100% (1.0)

5 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate (lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg)

6 Dermal MOE = POD (NOAEL of 40 mg/kg/ day)/ Daily dermal dose (mg/kg/day)

7 ST Inhalation MOE = POD (NOAEL of 40 mg/kg/ day) / Daily inhala tion dose (mg/kg/day)

8 Total MOE = 1/ (1/Dermal MOE + 1/Inhalation MOE)

9 Aerial applicators do not have baseline exposure: only engineering control expos ure can be assessed. All other exposure scenari os assess the baseline exposure scenario and baseline inhalation exposure.

10 These scenarios have baseline inhalation unit exposures , but not baseline dermal unit exposur es. The M/L/A scenario assessed in Table 5 results in a higher exposure (and ther efore is health protective) than either of the two “NA” scenarios shown at baseli ne plus gloves dermal exposure.

Table 7. Exposure and Risks for Occupational Handlers of Salicylaldehyde in Pesticide Products (All Exposure Durations) with Baseline Plus Gloves for High Acreage Mixer/ Loader Scenarios and Turf

Exposure Scenario

(Formulation/ Application/ Crop) Application

Rate 1 (lb inert/ A) Area
Treated Daily 2 (acres) Dermal
Unit Exposure

(mg/lb inert) 3 Inhalation
Unit Exposure

(ug/ lb inert) 3 Baseline +
Gloves
Dermal

Dose (mg/kg /day) 4 Baseline
Inhalation

Dose (mg/kg/

day) 5 Baseline +
Gloves
Dermal
MOE 6 Baseline
Inhalation

MOE 7 Total MOE 8

Mixer/Loader Scenarios

Liquids/ Aerial Application/ High Acreage Crops (ST) 1.456

1200 0.023 1.2 0.57408 0.029952 70 1300 66

Liquids/ Aerial Application/ High Acreage Crops (IT) 0.28 0.1104 0.00576 360 6900 340

Liquids/ Groundboom/ High Acreage Crops (ST) 1.456 200 0.09568 0.004992 420 8000 40021 1 Application rates are based on maximum application rates of products containing inerts multiplied by 14% to convert to applicat ion rate of just inert. Applicatio n rates for Short-term (ST) expos ure risk estimates are based on ma ximum application rates. Appli cation
rates for Intermediate-term (IT) and long-term (LT) exposures are based on average application rates.

2 Area treated daily values are from the EPA HED estimates of acreage treat ed in a single day for each exposure scenario of conce rn.

3 Unit Exposure values are reported in PHED Surrogate Expos ure Guide dated August 1998 or from ORETF data. All exposure scenarios assess baseline plus gloves plus baseline inhalation exposure except for ae rial applicator scenarios, which assess inhalation and dermal exposures with engineering controls.

4 Daily Dermal Dose = (Dermal Unit Exposure (mg inert /lb inert) * Application Rate (lb inert /A) * Area Treated (A /day))/ Body Weight (70 kg) * Dermal Absorption Factor of 100% (1.0)

5 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate (lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg)

6 Dermal MOE = POD (NOAEL of 40 mg/kg/ day)/ Daily dermal dose (mg/kg/day)

7 ST Inhalation MOE = POD (NOAEL of 40 mg/kg/ day) / Daily inhala tion dose (mg/kg/day)

8 Total MOE = 1/ (1/Dermal MOE + 1/Inhalation MOE) *Aerial applicators do not have baseline exposure: only engineering control expos ure can be assessed. All other exposure scenar ios assess baseline plus gloves and baseline inhalation exposure.

B. Occupational Postapplication Risk

The Agency uses the term postapplication to describe exposures that occur when individuals are present in an environment that ha s been previously treated with a pesticide (also referred to as re-entry exposure) . Such exposures may occur when workers enter previously treated areas to perform job functions, in cluding activities related to cr op production, such as scouting for pests or harvesting. Postapplication exposure leve ls vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation pr operties. In addition, the timing of pesticide applications, relative to harves t activities, can greatly reduce the potential for postapplication

exposure.

Inhalation exposures are not typically cal culated for occupati onal post-application scenarios because inhalation exposures generally acc ount for a negligible percentage of the overall body burden for most pesticide chemicals.

Exposure Scenarios

This assessment is considered to be a screen ing level estimate, demonstrating that there are minimal potential risks to workers re-entering fields treated with pesticides containing salicylaldehyde as an in ert ingredient. While salicylaldehyde may be present in formulations designated for crops besides those assessed in this document, risk estimates for those occupational postapplication scenarios are expected to be less than those scenarios a ssessed in this document (i.e., calculated MOEs will be higher). The three occupational postapplication scenarios assessed are for postapplication activities associated with:

 Tall field/row crops (including scouti ng, weeding, hand harvesting sweet corn) Liquids/ Groundboom/ High Acreage Crops (IT) 0.28 0.0184 0.00096 2200 42000 2100

Liquids/ Groundboom/ Turf (ST) 1.456 40 0.019136 0.000998 2100 40000 2000

Liquids/ Groundboom/ Turf (IT) 0.28 0.00368 0.000192 11000 210000 10000

Wettable Powder/ Groundboom/ High Acreage Crops (ST) 0.224

200 0.17 43 0.1088 0.02752 370 15003 290

Wettable Powder/ Groundboom/ High Acreage Crops (IT) 0.14 0.068 0.0172 590 2300 47022  Turf (golf course/sod farm) (includi ng mowing, transplant ing, hand weeding)

 Vine/Trellis crops (including sc outing, training, tying, thinning, and grape girding and cane turning)

Exposure Data and Assumptions

The assumptions used in the postapplication risk assessment calculations are detailed as
follows:

 The average occupational workday is assumed to be 8 hours.

 The adverse effects for the short- and interm ediate-term dermal POD’s are based on studies
where the effects were observed in both se xes; therefore, the body weight of 80 kg was used to estimate exposure (HED HotSheet #31, 1/17/12).

 HED has developed standard transfer coeffi cient values for occupational postapplication
scenarios to ensure consistenc y in exposure assessments. Thes e standard values were used to calculate postapplication exposures.

 Anticipated post-application activities and thei r respective dermal transfer coefficients (TCs) are summarized in Table 8. The TC info rmation is based on the Science Advisory Council for Exposure Policy Number 3.1.

 The transfer coefficient for sod transplanti ng, and hand weeding used to represent dermal exposure is from Agriculture Reentry Ta sk Force (ARTF) data; study ARF-035 (MRID 45432303).

 Calculations of postapplicati on exposures are completed usi ng maximum application rates of pesticide products for short-term exposures and average applicati on rates of pesticide products for intermediate-term exposures.

 No postapplication data were submitted for salicylaldehyde; a default 50% of the application rate (for agricultu ral crops) and 10% (for turf) is considered available as a
transferrable residue with a 10% default daily dissipation rate.

 Dermal absorption is assumed to be 100%.

Risks were calculated using the MOE appro ach, which is a ratio of the exposure to the toxicological PoD.

Risk Characterization

A variety of pesticide formulations may contain salicylaldehyde. PPE is usually not required for worker re-entry, a nd therefore these postapplication risk estimates are based on the baseline exposure scenario (i.e., typical work clothing but no gloves). Typically, the Agency
characterizes the risk estimate in relation to the restricted entry interval (REI) for a particular active ingredient. While REIs for specific product s are not discussed in this risk assessment, occupational post-application scen arios assessed generally result in MOEs that do not indicate risks of concern on Day 0 (the day of applica tion) except for ten postapplication scenarios.

Occupational postapplication risk estimates are presented in Table 8. The risk estimates for the three exposure scenarios assessed resulted in MO Es do not demonstrate risks of concern (i.e., MOEs > 100) on Day 0, except for ten scenarios:23 1) The short- and intermediate-term worker postapplication activitie s involving herbicides on corn, specifically the hand-harv esting harvesting/ detassl ing scenario. That scenario resulted in
a short-term MOE of 7 and an intermediate-term MOE of 62 on the day of application (Day 0). Assuming an herbicide applicati on at the maximum application ra te, the short-term MOE would exceed 100 for this scenario at day 25 after a pplication and the interm ediate-term MOE would exceed 100 at day 5 after applicatio n. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same da y workers would be conducting hand harvesting and detassling activities. As noted earlier in this assessment, herbicides are typically applied relatively earl y in a growing season.

2) The short- and intermediate-term worker postapplication activitie s involving herbicides on grape, table, specifica lly the harvest, pull, thi n, prune, train, tie scenario. That scenario resulted
in a short-term MOE of 53 and an intermediate-t erm MOE of 90 on the day of application (Day 0). For the short-term, assuming an herbicide appli cation at the maximum a pplication rate, the MOE would exceed 100 for this scenario at day 6 after application. For the intermediate-term, assuming an herbicide application at the maximum appli cation rate, the MOE woul d exceed 100 for this scenario at day 1 after applica tion. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same day wo rkers would be conducting harvest, pull, thin, prune, train, tie activities. As noted ear lier in this assessment, herbicides are typically applied relatively earl y in a growing season.

3) The short- and intermediate-term worker postapplication activitie s involving herbicides on grape, table, specifically the cane turning, gird ling scenario. That scenario resulted in a shortterm MOE of 27 and an intermediate-term MOE of 45 on the day of application (Day 0). For the short-term, assuming an herbicid e application at the maximum a pplication rate, the MOE would exceed 100 for this scenario at day 13 after appl ication. For the intermediate-term, assuming an herbicide application at the maximum appli cation rate, the MOE would exceed 100 for this scenario at day 8 after applica tion. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same day workers would be conducting hand cane turning, girdling activities.

4) The short-term worker postapplication activities involving herbicides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 72 on the day of application (Day 0). Assuming an herbic ide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 3 after application. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on th e same day workers would be conducting transplant, weed, harv est activities. As noted earlier in this assessment, herbicides are typically applied relativel y early in a growing season.

5) The short-term worker postapplication activities involving in secticides on corn, specifically the hand-harvesting harvesting/ detassli ng scenario. That scenario resulted in an MOE of 20 on the day of application (Day 0). Assuming an insectic ide application at the maximum application rate, the MOE would exceed 100 for th is scenario at day 16 after application. The Agency notes that it is not expect ed to be typical agricultural pract ice to apply insecticides on the same day workers would be conducting hand harves ting and detassling activiti es. As noted earlier in this assessment, insecticides are typically applied relatively early in a growing season.24 6) The short- term worker postapplication activ ities involving insecticides on grape, table, specifically the cane turning, girdlin g scenario. That scenario result ed in a short-term MOE of 37 on the day of application (Day 0). For the short-te rm, assuming an insecticide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 10 after application. The Agency notes that it is not expect ed to be typical agricultural practice to apply insecticides on the same day workers would be conducting hand cane turning, girdling activities.

7) The short-term worker postapplication activities involving in secticides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 47 on the day of application (Day 0). Assu ming an insecticide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 6 after application. The Agency notes that it is not expected to be typical agricultural practic e to apply insecticides on the same day workers would be conducting transplant, weed, harvest activ ities. As noted earlier in this assessment, insecticides are typically applied relatively early in a growing season.

8) The short-term worker postapplicati on activities involving fungicides on corn, specifically the hand-harvesting harvesting/ detassli ng scenario. That scenario resulted in a shortterm MOE of 37 on the day of a pplication (Day 0). Assuming a fungicide application at the maximum application rate, the s hort-term MOE would exceed 100 for this scenario at day 9 after application. The Agency notes that it is not expect ed to be typical agricultural practice to apply fungicides on the same day workers would be c onducting hand harvesting a nd detassling activities.
As noted earlier in this assessmen t, fungicides are typically applie d relatively earl y in a growing

season.

9) The short-term worker postapplication activ ities involving fungici des on grape, table, specifically the cane turning, girdlin g scenario. That scenario result ed in a short-term MOE of 64 on the day of application (Day 0). For the short- term, assuming a fungici de application at the maximum application rate, the MOE would exceed 100 for this scenario at day 4 after application. The Agency notes that it is not expected to be typical agricultural practice to apply fungicides on the same day workers would be conducti ng hand cane turning, girdling activities.

10) The short-term worker postapplicati on activities involving fungicides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 94 on the day of application (Day 0). Assu ming a fungicide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 1 af ter application. The Agency notes that it is not expected to be typical agricultu ral practice to apply fungicides on the same day workers would be conducting transplant, weed, harvest activities. As not ed earlier in this assessment, insecticides are typically applied relatively early in a growing season.

All other insecticide postapplication scenarios result in MOEs that do not demonstrate risks of concern on the day of application (Day 0).

A variety of pesticide formulations may c ontain salicylaldehyde. PPE is usually not required for worker re-entry, a nd therefore these postapplication risk estimates are based on the baseline exposure scenario (i.e., typical work clothing but no gloves). Typically, the Agency25 characterizes the risk estimate in relation to the restricted entry interval (REI) for a particular active ingredient. While REIs for specific product s are not discussed in this risk assessment, occupational post-application scen arios assessed result in MOEs that do not indicate risks of concern on Day 0 (the day of application).

Table 8. Short- and Intermediate-Term Occupational Postapplication Dermal Exposures and Risks for Salicylaldehyde
Crop & Exposure
Duration Application
Rate (lb inert /A) Work Activity Transfer
Coefficient 1

(cm 2 /hr) Day after
Treatment 2 DFR t (μg/cm 2 ) 3 Daily Dose (mg/kg/day) 4 MOE 5

Herbicide Product Scenarios

Corn (ST) 1.456 Scout, weed low foliage 100 0

3.27 0.0327 1200

Scout, weed high foliage 400 0 0.1306 310

Scout, irrigate,

weed high

foliage 1,000 0 0.3265 120

Harvesting/ detassling 17,000 0 5.5513 7

Corn (IT) 0.168 Scout, weed low foliage 100 0

0.377 0.0038 11000

Scout, weed high foliage 400 0 0.0151 2700

Scout, irrigate,

weed high

foliage 1,000 0 0.0377 1100

Harvesting/ detassling 17,000 0 0.6405 62

Grapes (Table)

(ST) 0.672 Hedge, irrigate, weed, scout,

train, tie 500 0

1.51 0.0754 530

Scout, train, tie 1,000 0 0.1507 270 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.7536 53

Cane turning, girdle 10,000 0 1.5071 27

Grapes (Table)

(IT) 0.392 Hedge, irrigate, weed, scout,

train, tie 500 0

0.879 0.0440 910

Scout, train, tie 1,000 0 0.0879 460 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.4396 90

Cane turning, girdle 10,000 0 0.8792 45

Turf/ sod

(ST) 1.456 Mowing 500 0
0.816 0.0408 980

Transplant, weed, harvest 6,800 0 0.5551 72

Turf/ Sod (IT) 0.168 Mowing 500 0 0.094 0.0047 850026 Table 8. Short- and Intermediate-Term Occupational Postapplication Dermal Exposures and Risks for Salicylaldehyde
Crop & Exposure
Duration Application
Rate (lb inert /A) Work Activity Transfer
Coefficient 1

(cm 2 /hr) Day after
Treatment 2 DFR t (μg/cm 2 ) 3 Daily Dose (mg/kg/day) 4 MOE 5

Transplant, weed, harvest* 6,800 0 0.0641 620

Insecticide Product Scenarios

Corn (ST) 0.56 Scout, weed low foliage 100 0

1.26 0.0126 3200

Scout, weed high foliage 400 0 0.0502 800

Scout, irrigate,

weed high

foliage 1,000 0 0.1256 320

Harvesting/ detassling 17,000 0 2.1351 20

Corn (IT) 0.056 Scout, weed low foliage 100 0

0.126 0.0013 32000

Scout, weed high foliage 400 0 0.0050 8000

Scout, irrigate,

weed high

foliage 1,000 0 0.0126 3200

Harvesting/ detassling 17,000 0 0.2135 190

Grapes (Table)

(ST) 0.28 Hedge, irrigate, weed, scout,

train, tie 500 0

0.628 0.0314 1300

Scout, train, tie 1,000 0 0.0628 640 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.3140 130

Cane turning, girdle 10,000 0 0.6280 64

Grapes (Table)

(IT) 0.168 Hedge, irrigate, weed, scout,

train, tie 500 0

0.377 0.0188 2100

Scout, train, tie 1,000 0 0.0377 1100 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.1884 210

Cane turning, girdle 10,000 0 0.3768 110

Turf/ sod

(ST) 0.56 Mowing 500 0
1.26 0.0628 640

Transplant, weed, harvest 6,800 0 0.8540 47

Turf/ Sod (IT) 0.056 Mowing 500 0
0.00314 0.0016 26000

Transplant, weed, harvest* 6,800 0 0.0214 1900

Fungicide Product Scenarios27 Table 8. Short- and Intermediate-Term Occupational Postapplication Dermal Exposures and Risks for Salicylaldehyde
Crop & Exposure
Duration Application
Rate (lb inert /A) Work Activity Transfer
Coefficient 1

(cm 2 /hr) Day after
Treatment 2 DFR t (μg/cm 2 ) 3 Daily Dose (mg/kg/day) 4 MOE 5

Corn (ST) 0.28 Scout, weed low foliage 100 0

0.628 0.0063 64000

Scout, weed high foliage 400 0 0.0251 1600

Scout, irrigate,

weed high

foliage 1,000 0 0.0628 640

Harvesting/ detassling 17,000 0 1.0676 37

Corn (IT) 0.056 Scout, weed low foliage 100 0

0.126 0.0013 32000

Scout, weed high foliage 400 0 0.0050 8000

Scout, irrigate,

weed high

foliage 1,000 0 0.0126 3400

Harvesting/ detassling 17,000 0 0.2135 190

Grapes (Table)

(ST) 0.28 Hedge, irrigate, weed, scout,

train, tie 500 0

0.628 0.0314 130

Scout, train, tie 1,000 0 0.0628 640 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.3140 130

Cane turning, girdle 10,000 0 0.6280 64

Grapes (Table)

(IT) 0.112 Hedge, irrigate, weed, scout,

train, tie 500 0

0.251 0.0126 3200

Scout, train, tie 1,000 0 0.0251 1600 Harvest, pull,

thin, prune,

train, tie 5,000 0 0.1256 320

Cane turning, girdle 10,000 0 0.2512 160

Turf/ sod

(ST) 0.28 Mowing 500 0
0.628 0.0314 1300

Transplant, weed, harvest* 6,800 0 0.4270 94

Turf/ Sod (IT) 0.056 Mowing 500 0
0.0.0314 0.0016 26000

Transplant, weed, harvest* 6,800 0 0.0214 1900

1 The TC from this exposure scenario uses ARTF data - study ARF-035 (MRID 45432303).

2 Day after Treatment set to 0 by default

3 Dislodgable Foliar Residue (μg/cm 2 ) = AR * F * (1-D) t * CF1 * CF2. Where: AR = Application Rate (lb inert/acre), F = fraction of ai retained on foliage or 20% for foliar crop or 5% for turf (unitless), D = fraction of residue that dissipates daily or 10% (unitless), t = number of da ys after application day (days), CF1 = 4.54 x 10 8 μg/lb, CF2 = 24.7
x 10 -9 acre/cm 228 4 Daily Dermal Dose (mg/kg/day) = DFR t * CF3 * Tc * DA * ET/BW (kg). Where: DFRt = dislodgable foliar residue on day “t” (μg/cm 2 ), CF3 = 1 x 10 -3 mg/μg, Tc = transfer coefficient (cm 2 /hr), DA = dermal absorption factor 100% (unitless) default with no data submitted, ET = exposure time 8 (hr/day), BW = body weight 80 (kg) (HED Hot Sheet #31, 1/17/12)

5 Margin of Exposure: MOE = POD (40 mg/kg/day) / DDD (mg/kg/day). MOE (unitless), POD = Point of Departure usually NOAEL = No Observed Adverse Effect Level: Dose level in a toxicity study, DDD = Dermal Daily Dose: the absorbed dose received from exposure to a pesticide in a given scenario.

VIII. CUMULATIVE EXPSOURE

Cumulative effects from substances with a common mechanism of toxicity . Section 408(b)(2)(D)(v) of FFDCA requires th at, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available info rmation” concerning the cumulative effects of a particular pesticide's residues and “other substanc es that have a common mechanism of toxicity.”

EPA has not found salicylaldehyde to share a common mechanism of toxicity with any other substances, and that salic ylaldehyde does not appear to pr oduce a toxic metabolite produced by other substances. For the purposes of this to lerance action, therefore, EPA has assumed that salicylaldehyde does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determin e which chemicals have a common mechanism of toxicity and to evaluate the cumulative effect s of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative

.

IX. ENVIRONMENTAL JUSTICE STATEMENT

Potential areas of environmental justice concerns , to the extent possible, were considered in this human health risk assessment, in accord ance with U.S. Executive Order 12898, "Federal
Actions to Address Environmental Justice in Mino rity Populations and Lo w-Income Populations," http://www.eh.doe.gov/oepa/ guidance/justice/eo12898.pdf

.

As a part of every pesticide risk assessment , OPP considers a large variety of consumer subgroups according to well-establis hed procedures. In line with O PP policy, RD estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consumption, and activities in and ar ound the home that involve pesticide use in a residential setting. Extensive data on food cons umption patterns are co mpiled by the USDA under CSFII and are used in pesticide risk assessments fo r all registered food uses of a pesticide. These data are analyzed and categorized by subgroups ba sed on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performe d when conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for t oddlers, youths, and adults entering or playing on treated areas post-application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the de velopment of specialized software and models that consider exposure to bystanders and farm work ers as well as lifestyle and traditional dietary patterns among specific subgroups29 X. ENVIRONMENTAL FATE CONSIDERATIONS

Salicylaldehyde is expected to have high biologi cal oxygen demand, and it is expected to cause significant oxygen depletion in aquatic systems. It has a hi gh potential to affect aquatic organisms and the growth of some plants. It has a moderate potential to affect secondary waste treatment microorganisms and the ge rmination of some plants. This chemical is expected to be biodegradable and is not likely to bioconcentrate. The direct instan taneous discharge to a receiving body of water of an amount of this chemical which will rapidly produce, by dilution, a final concentration of 0.1 mg/L or less is not expected to cause an adverse environmental effect. After dilution with a large amount of water, followed by secondary waste treatment, this chemical is not expected to have any adverse environmental impact.

XI. ECOTOXICITY

Salicylaldehyde has been tested for eco logical toxicity. Based on the studies, salicylaldehyde has the potential to affect aquatic organisms. The chemical is ready biodegradable and not expected to have advers e ecological effects due to dilu tion factor and biodegradability potential. A summary of the ecologica l toxicity is presented below:

Table 9 Ecotoxicity of Salicylaldehyde Test Organism Result
96 hour LC 50 Fathead
Minnow 3.2 uL/L

96 hour LC 50 Water Flea 3.0 uL/L

24 hour LC 50 Water Flea 6.8 mg/L

Salicylaldehyde is a naturally occurring ben zaldehyde found in food and is also used as a food additive. It is Generally Regarded as Safe (GRAS) with a human aver age daily intake of 16 ug/day and an annual natural occurrence in 66,47 0 kg of food per year. As a component of pesticides, up to 448 gm/acre of salicylaldehyde ma y be applied to a crop in a year. Based on the above toxicological data, potenti al residues of salicylaldehyde ar e unlikely to exceed the amount found naturally in foods and currently ingested.

XII. RISK CHARACTERIZATION

Ag-Chem Consulting LLC, 122O8 Quinque La ne, Clifton VA 20124 on behalf of Omex Agrifluids, 24730 Avenue 13, Madera CA 93637 pr oposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180.910 to establish an exemption from the requi rement of a toleran ce for salicylaldehyde (salicylaldehyde) (CAS# 90-02-8 ) in or on food crops at no more than 14% of the pesticide formulation to help the active ingr edient properly penetrat e and remain available to act in the soil.

The approximate acute oral LD 50 's of salicylaldehyde were 566 mg/kg/day for male rats and 504 mg/kg/day for male mice due to slight to severe weakness, salivation, prostration and
death.30 Salicylaldehyde produced strong skin irrita tion to guinea pigs. The acute dermal LD 50 vas greater than 20 ml/kg for the gui nea pig. The highest dose tested produced tremors which may be an indication of percutaneous absorption. Repeat ed applications (10) to the uncovered clipped backs of guinea pigs produced m oderate exacerbation of the irritative response. None of five guinea pigs tested for allergic skin reactions exhi bited a positive response. Eye irritation tests were not done, however, based on the severe skin reac tion, it is assumed that this compound would produce severe eye irritation.

A single dose of salicylaldehyde was administer ed to a fasted rabbit. Approximately 75%
of the dose was excreted in the urine collected ov er 24 hr revealing ether soluble acids, with 27% and 3% accounted for as glucuronic acid and sulf ate conjugates of vanillic acid, respectively.

Repeated dose toxicity and reproductive deve lopmental toxicity combined test based on oral administration using salicylaldehyde rats, we used dosages of 0 (contrast group), 2.5, 10, 40, and 160 mg/kg/day. No effects of administration of th e tested substance to ma le rats were found in general conditions, weight, feed volume, hematologi cal test values, blood chemistry test values, autopsy findings, and organ weight . In the tested substance admi nistration groups of 40 mg/kg/day or more, the degree of lobular pe ripheral adiposity in the liver and the frequency of appearance was less than in the contrast group. This is not considered to be an adverse effect. In the test on female rats, aside from one mother in the 40 mg/kg/day administration group that was partway through parturition on pregnancy Day 22, and one mother in the 160 mg/kg/day administration group that died on pregnancy Day 22, no changes we re observed in the general condition. In the 160 mg/kg administration group, the liver weight showed a high value, and the ovaries a low value. However, no effects of administration of the tested substance were found in weight, feed volume, and autopsy findings. In the tested subs tance administration groups of 40 mg/kg/day or more, a slight increase in the glycogen volume wa s observed inside liver cells. From the above, we concluded that general toxicologi cal effects under the test conditions showed no adverse effects in both males and females at 40 mg/kg/day. No effects of administration of the tested substance were found on the female estrus cycle and estrus count, on the male and female mating and impregnation, and on the female animal pre gnancy period and parturition. No nursing
abnormalities were found in the tested substan ce administration groups of 40 mg/kg or less. Nevertheless, in the 160 mg/kg administration gr oup, two cases of mother animals were found in which all infants had died by Day 4 of nursing. No e ffects of administration of the tested substance
were found in the number of live birth female s, delivery rate, luteal number, number of implantation scars, and implantation rate. No effect s of administration of the tested substance were found on nursing Day 0 in the number of live birt h infants, number of stillborns, sex ratio, parturition rate, and birth rate. No outward abnorm alities were found that coul d be considered to be
traced to the tested substance administration in newborn infant s and stillborns. A large trend toward infant deaths during the nursing period was seen in the 160 mg/kg/day administration group, and there was a low trend for newborn infant live birth rates on Day 4 of nursing in this same group. In addition, the wei ghts on nursing Day 0 and Day 4 show ed a trend toward a slightly low value in the 160 mg/kg/day administrati on group. From the above, we concluded that reproductive developmental toxicolo gical effects under the test c onditions showed no effects for males at 160 mg/kg/day, for females at 40 mg/kg/ day, and for newborn infants at 40 mg/kg/day.31 Male and female rats [Crl:CD(SD), 7 weeks at time of administrati on] were used to study the presence or absenc e of salicylaldehyde micronucleus indu cement in rat bone marrow cells. In five animals per one group, the tested substance wa s forcibly orally administered to males at 50, 100, 200, and 400 mg/kg, and to females at 25, 5 0, 100, and 200 mg/kg, on two times with an
interval of 24 hours. Since no death cases were found in any of the administration groups, we looked for the appearance frequency of PCE (MNP CE) with micronucleus, for all animals in the negative contrast group, the tested substa nce administration groups of 100, 200, and 400 mg/kg/day groups (male), and of 50, 100, and 200 mg/kg/day groups (female), and the positive contrast group. As a result, for both males a nd females, in the tested substance groups no significant increase in the MNPCE count was seen in any of the groups in comparison with the negative contrast group. The average value of the MNPCE appearance frequency and PCE ratio in the negative contrast group was in every case within the range of the test facility background values, and in the negative contrast group a sign ificantly clear micronucleus inducement was seen. Therefore, we concluded that th is test was suitably implemen ted. From the above results, we judged that the tested substance salicylalde hyde had micronucleus te st negativity; it has no clastogenicity in rat bone marrow cells.

The salicylaldehyde in vitro chromosome aberration inducemen t was studied using Chinese hamster cultured cells (CHL/IU), and a positive result was obtained. The concentrations of 0.020 mg/mL for the continuous process, and 0.20 mg/mL/ for the short-time process, were set as the maximum process concentration for this test. On e-half and one-fourth concentrations of the maximum process concentration were set as th e medium concentration and low concentration, respectively. As a result of 24-hour and 48-hour continuous processing, the CHL/IU cells showed a significant increase of cells having chromosome structural aber rations, in the 24-hour process high-concentration group (0.020 mg/mL), and signifi cance was obtained in the trend test as well. In addition, in the 48-hour pro cess high-concentration group (0.020 mg /mL/), a significant increase of cultured cells was seen, and a significant diffe rence in the trend test was obtained as well. Meanwhile, the groups with 6-hour processing u nder S9 mix existence and non-existence were both dependent on the concentration, with a significant increase in ce lls with structural aberrations. In addition, the group under S9 mix existence was dependent on the concentration, with a significant increase in polyploidy cells.

A reverse mutation test using bacteria was used to investig ate the presence or absence of salicylaldehyde mutagenicity, and this test obtained a negative resu lt. For the assay bacteria, five
bacterial strains we re used, including Salmonella typhimurium TA100, TA1535, TA98, TA1537,
and Escherichia coli WP2 uvr A, and a dosage setting test was performed for this test using the plate method with S9 mix no-additive and additi ve conditions. When the dosage setting test was performed at a dosage of 50 to 5000 ug/plate, in the S9 mix no-additive, antibiotic action was found at dosages of 1500 ug/plate or more (TA 100 at 500 ug/plate or more, and WP2 uvr A at 5000 ug/plate or more), while in the S9 mix addi tive, it was found at 150 0 ug/plate or more (TA 100 at 500 ug/plate or more). In this test, the S9 mix no-additive test was set at dosages in a range of 31.3 to 1000 ug/plate (TA100 at 15.6 to 500 ug/plate, and WP2 uvr A at 125 to 4000 ug/plate),
and the S9 mix additive test was set at 62.5 to 2000 ug/plate (TA 100 at 15.6 to 500 ug/plate, and
WP2 uvr A at 125 to 4000 ug/plate), and the test was implemented. As a result, in both of the two rounds of tests, since no increase was found in th e revertant colony numbers that were more than
double the solvent contrast value in all dosages of the five types of assay strain used, we concluded that salicylaldehyde does not have any mutageni city (negative) in the test system used.32 For chronic toxicity, data from the repeated dose toxicity study was used. In the repeated dose toxicity study, no effects of administration of the tested substance were found in general conditions, weight, feed volume, hematological test values, blood chemistry test values, autopsy findings, and organ weight were found on males. In the tested substance administration groups of 40 mg/kg or more, the degree of lobular peripheral adiposity in the liver and the frequency of appearance was less than in the co ntrast group in males. The effects on females were aside from one mother in the 40 mg/kg administration gr oup that was partway through parturition on pregnancy Day 22, and one mother in the 160 mg/kg administration group that died on pregnancy Day 22, no changes were observed in the gene ral condition. In the 160 mg/kg administration female group, the liver weight showed a high valu e, and the ovaries a low value. However, no
effects of administration of the tested substance were found in we ight, feed volume, and autopsy findings in females. In the tested substance ad ministration female groups of 40 mg/kg or more, a slight increase in the glycoge n volume was observed inside liver cells. From the above, we concluded that general toxicologi cal effects under the test conditions showed no adverse effects in both males and females at 40 mg/kg/day. No effects on reproductive developmental toxicity in parent animals of the tested substance were f ound on the female estrus cycle and estrus count, on the male and female mating and impregnation, an d on the female animal pregnancy period and parturition. No nursing abnormalities were found in the tested subs tance administration groups of 40 mg/kg or less. Nevertheless, in the 160 mg /kg administration group, two cases of mother
animals were found in which all infants had died by Day 4 of nursing. No effects of administration
of the tested substance were found in the number of live birth females, delivery rate, luteal number, number of implantation scars, a nd implantation rate. No effects of administration of the tested substance were found on nursing Day 0 in the number of live birth infants, number of stillborns, sex ratio, parturition rate, and birth rate. No outward abnormalities were found that could be
considered to be traced to the tested substan ce administration in newborn infants and stillborns. A large trend toward infant deaths during the nursing period was seen in the 160 mg/kg administration group, and there was a low trend fo r newborn infant live birth rates on Day 4 of nursing in this same group. In addition, the weig hts on nursing Day 0 and Day 4 showed a trend toward a slightly low value in the 160 mg/kg administration group. From the above, we concluded that reproductive developmental toxicological effects under the te st conditions showed no effects for males at 160 mg/kg/day, for females at 40 mg/kg/day, and for newborn infants at 40 mg/kg/day.

There are no cancer studies av ailable for salicylaldehyde. Sali cylaldehyde is metabolized mainly to ether soluble acids, with 27% and 3% accounted for as gluc uronic acid and sulfate conjugates of vanillic acid, respectively. These metabolites are generally recognized as safe: glucuronic acid is a precursor of ascorbic acid (Vitamin C) and vanillic acid is a common food additive. Based on predicted rapid metabolism and ex cretion, lack of specific target organ toxicity in the repeat dose studies study a nd lack of mutagenici ty, salicylaldehyde is not expected to be carcinogenic.

The FQPA Safety Factor (as required by th e Food Quality Protection Act of 1996) is intended to provide an additional l0-fold safety f actor (10X), to protect for special sensitivity in
infants and children. Based on available informa tion discussed thus far and below in Special Consideration for Infants and Children, the FQPA safety factor shoul d be reduced to IX.33 No acute toxicological endpoint of concer n has been identifie d for salicylaldehyde. On the
basis of the r epeated d ose and reproductive/developmental toxicity s creening study, a NOAEL for parental systemic toxicity and embryo/developm ental toxicity NOAEL for salicylaldehyde was 40 mg/kg bw/day. As summarized above, the available toxicology data support that the FQPA safety factor for salicylaldehyde should be reduced from 10X to IX. Therefore, only the 10X factors for intra- and inter- species variability should be included in ca lculating the chronic reference dose (cRfD) and the chronic populati on adjusted dose (cPAD). The chr onic reference dose (cRfD) is therefore 0.4 mg/kg (40 mg/kg bw/day /100). The chronic NOAEL is also a pplicable to the dermal and inhalation exposure routes.

No adverse effects attributable to a single exposure to salicy laldehyde were seen in the toxicity databases; ther efore, an acute dietary risk assessmen t is not a concern. A chronic dietary
risk assessment takes into account exposure estimates from chroni c dietary consumption of food and drinking water. Model estimates for oral exposu re from the use of salicy laldehyde in pesticidal formulations (including exposur e through drinking water) resulte d in chronic dietary exposure estimates for food and drinking water below the Ag ency’s level of concern (<100% cPAD) for the U.S. population and all population subgroups. The ch ronic dietary exposure from food and water to salicylaldehyde is 13% of the cPAD for th e U.S. population and also 49% of the cPAD for children 1-2 years old, the most highly expos ed population subgroup. The Agency has not identified any concerns for carcinogenicity relating to salicylaldehyde; therefore, a cancer dietary exposure assessment was not performed.

The term “residential exposure” is used in this document to refer to non-occupational, nondietary exposure (e.g., for lawn and garden pest cont rol, indoor pest control, termiticides, and flea and tick control on pets). While there are no current or proposed re sidential uses for salicylaldehyde, it is possible that salicylaldehyde may be used as an inert ingredient in pesticide products for which short-term and intermediate-t erm residential exposures may result. In the absence of specific residential e xposure scenarios, risk estimates for residential exposures to salicylaldehyde can be modeled based on occupati onal exposure assessments for salicylaldehyde. Occupational exposure assessments for salicylald ehyde for occupational mixer/loader/applicator exposure and occupational post-application expo sure for comparable use scenarios (e.g., low pressure handwand turf application) with only ba seline personal protective equipment result in MOEs of 500 or greater (i.e., e xposures are not of concern). Give n the larger treatment areas and higher concentrations of salicyla ldehyde used in these occupationa l use pesticide products than would be seen in residential uses, MOEs for re sidential use scenarios would exceed 1,000 or more
and therefore there are no concerns for re sidential exposures to salicylaldehyde.

There was no hazard attributable to a single expo sure seen the in the toxicity database for salicylaldehyde; therefore, an acute aggr egate risk assessment is not required.

The chronic exposure to salicyla ldehyde from food and water is conservatively estimated to utilize 49% of the cPAD for children 1-2 yr s old, the population group receiving the greatest exposure. Chronic residential exposure to re sidues of salicylalde hyde not expected.

Short- and intermediate term aggregate exposur e takes into account s hort-term residential exposure plus chronic exposure through food and drinking water (c onsidered to be a background34 exposure level). Since it is possible that salicylal dehyde may be used as an inert ingredient in pesticide products for which short-term and interm ediate-term residential exposures may result, the Agency has determined that it is appropriate to aggregate chronic exposure through food and water with short-term residential exposures to sa licylaldehyde. Using the exposure assumptions described in this unit for short-term exposures, EPA has concluded the combined short-term food, water, and residential exposures result in aggregate MOEs of 430 for adults and 170 for children (1-2 years old). Because EPA's le vel of concern for salicylaldehyde is a MOE of 100 or below,
these MOEs are not of concern.

The Agency has not identified any concerns for carcinogenicity for salicylaldehyde; therefore, an aggregate cancer expo sure assessment was not performed.

EPA has determined that exposure to handler s as the result of us ing pesticide products which might potentially contain sa licylaldehyde as an inert ingred ient may occur in a variety of occupational environments. The representative occ upational scenarios select ed by the Agency for assessment were evaluated based on likely maxi mum application rates for products which may contain salicylaldehyde as an in ert ingredient for the short-term exposure assessment, and average application rates for products li kely to contain salicylaldehyde as an inert ingredient for the intermediate- and long-term exposur e durations. Active ingredient ap plication rates were corrected
for the maximum amount of the inert ingredient likely to be in the final formulations to determine exposure and risk from exposure salicylaldehyde . A summary of the occupational assessment is presented below.

RD initially assessed handler exposure and risks for salicylaldehyde in pesticides at baseline PPE (long pants, a long-sleeved shirt, s hoes, socks, no chemical-resistant gloves, and no respiratory protection) which the Agency consid ers to be the typical minimal worker clothing.
When these assessments indicated that there were potential risks of concern for scenarios where workers would be handling larg e quantities of pesticide for high volume operations typically involving aerial applications to high acreage crops, RD repeated the assessments and included additional PPE (i.e., chemical-resistant gloves fo r pesticide handlers). The Agency believes workers handling large volumes of pesticides w ill be wearing chemical-resistant gloves. When handlers are wearing typical work er clothing (i.e., ba seline PPE) the majority of occupational
handler scenarios do not i ndicate risks of concern. For the occupational handler scenarios which involve the handling of large volumes of pesticid es, those which EPA believes that handlers will be wearing chemical-resistant gloves, occupati onal handler scenarios do not indicate risks of
concern with the addition of chem ical-resistant gloves to baseline PPE (i.e., baseline plus gloves).

The Agency uses the term postapplication to describe exposures that occur when individuals are present in an environment that ha s been previously treated with a pesticide (also referred to as re-entry exposure) . Such exposures may occur when workers enter previously treated areas to perform job functions, in cluding activities related to cr op production, such as scouting for pests or harvesting. Postapplication exposure leve ls vary over time and depend on such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation pr operties. In addition, the timing of pesticide applications, relative to harves t activities, can greatly reduce the potential for postapplication

exposure.35 Inhalation exposures are not typically cal culated for occupati onal post-application scenarios because inhalation exposures generally acc ount for a negligible percentage of the overall body burden for most pesticide chemicals.

A variety of pesticide formulations may c ontain salicylaldehyde. PPE is usually not required for worker re-entry, a nd therefore these postapplication risk estimates are based on the baseline exposure scenario (i.e., typical work clothing but no gloves). Typically, the Agency
characterizes the risk estimate in relation to the restricted entry interval (REI) for a particular active ingredient. While REIs for specific product s are not discussed in this risk assessment, occupational post-application scen arios assessed generally result in MOEs that do not indicate risks of concern on Day 0 (the day of applicatio n) except for three postapplication scenarios.

Occupational postapplication risk estimates for the three exposure scenarios assessed
resulted in MOEs do not demonstrate risks of concern (i.e., MOEs > 100) on Day 0, except for ten
scenarios:

1) The short- and intermediate-term worker postapplication activitie s involving herbicides on corn, specifically the hand-harv esting harvesting/ detassl ing scenario. That scenario resulted in
a short-term MOE of 7 and an intermediate-term MOE of 62 on the day of application (Day 0). Assuming an herbicide applicati on at the maximum application ra te, the short-term MOE would exceed 100 for this scenario at day 25 after a pplication and the interm ediate-term MOE would exceed 100 at day 5 after applicatio n. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same da y workers would be conducting hand harvesting and detassling activities. As noted earlier in this assessment, herbicides are typically applied relatively earl y in a growing season.

2) The short- and intermediate-term worker postapplication activitie s involving herbicides on grape, table, specifica lly the harvest, pull, thi n, prune, train, tie scenario. That scenario resulted
in a short-term MOE of 53 and an intermediate-t erm MOE of 90 on the day of application (Day 0). For the short-term, assuming an herbicide appli cation at the maximum a pplication rate, the MOE would exceed 100 for this scenario at day 6 after application. For the intermediate-term, assuming an herbicide application at the maximum appli cation rate, the MOE woul d exceed 100 for this scenario at day 1 after applica tion. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same day wo rkers would be conducting harvest, pull, thin, prune, train, tie activities. As noted ear lier in this assessment, herbicides are typically applied relatively earl y in a growing season.

3) The short- and intermediate-term worker postapplication activitie s involving herbicides on grape, table, specifically the cane turning, gird ling scenario. That scenario resulted in a shortterm MOE of 27 and an intermediate-term MOE of 45 on the day of application (Day 0). For the short-term, assuming an herbicid e application at the maximum a pplication rate, the MOE would exceed 100 for this scenario at day 13 after appl ication. For the intermediate-term, assuming an herbicide application at the maximum appli cation rate, the MOE would exceed 100 for this scenario at day 8 after applica tion. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on the same day workers would be conducting hand cane turning, girdling activities.36 4) The short-term worker postapplication activities involving herbicides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 72 on the day of application (Day 0). Assuming an herbic ide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 3 after application. The Agency notes that it is not expected to be typical agricultural practice to apply herbicides on th e same day workers would be conducting transplant, weed, harv est activities. As noted earlier in this assessment, herbicides are typically applied relativel y early in a growing season.

5) The short-term worker postapplication activities involving in secticides on corn, specifically the hand-harvesting harvesting/ detassli ng scenario. That scenario resulted in an MOE of 20 on the day of application (Day 0). Assuming an insectic ide application at the maximum application rate, the MOE would exceed 100 for th is scenario at day 16 after application. The Agency notes that it is not expect ed to be typical agricultural pract ice to apply insecticides on the same day workers would be conducting hand harves ting and detassling activiti es. As noted earlier in this assessment, insecticides are typically applied relatively early in a growing season.

6) The short- term worker postapplication activ ities involving insecticides on grape, table, specifically the cane turning, girdlin g scenario. That scenario result ed in a short-term MOE of 37 on the day of application (Day 0). For the short-te rm, assuming an insecticide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 10 after application. The Agency notes that it is not expect ed to be typical agricultural practice to apply insecticides on the same day workers would be conducting hand cane turni ng, girdling ac tivities.

7) The short-term worker postapplication activities involving in secticides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 47 on the day of application (Day 0). Assu ming an insecticide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 6 after application. The Agency notes that it is not expected to be typical agricultural practic e to apply insecticides on the same day workers would be conducting transplant, weed, harvest activ ities. As noted earlier in this assessment, insecticides are typically applied relatively early in a growing season.

8) The short-term worker postapplicati on activities involving fungicides on corn, specifically the hand-harvesting harvesting/ detassli ng scenario. That scenario resulted in a shortterm MOE of 37 on the day of a pplication (Day 0). Assuming a fungicide application at the maximum application rate, the s hort-term MOE would exceed 100 for this scenario at day 9 after application. The Agency notes that it is not expect ed to be typical agricultural practice to apply fungicides on the same day workers would be c onducting hand harvesting a nd detassling activities.
As noted earlier in this assessmen t, fungicides are typically applie d relatively earl y in a growing

season.

9) The short-term worker postapplication activ ities involving fungici des on grape, table, specifically the cane turning, girdlin g scenario. That scenario result ed in a short-term MOE of 64 on the day of application (Day 0). For the short- term, assuming a fungici de application at the maximum application rate, the MOE would exceed 100 for this scenario at day 4 after application.37 The Agency notes that it is not expected to be typical agricultural practice to apply fungicides on the same day workers would be conducti ng hand cane turning, girdling activities.

10) The short-term worker postapplicati on activities involving fungicides on turf, specifically the transplant, weed, harvest scenario. That scenario resulted in an MOE of 94 on the day of application (Day 0). Assu ming a fungicide application at the maximum application rate, the MOE would exceed 100 for this scenario at day 1 af ter application. The Agency notes that it is not expected to be typical agricultu ral practice to apply fungicides on the same day workers would be conducting transplant, weed, harvest activities. As not ed earlier in this assessment, insecticides are typically applied relatively early in a growing season.

All other insecticide postapplication scenarios result in MOEs that do not demonstrate risks of concern on the day of application (Day 0).

A variety of pesticide formulations may c ontain salicylaldehyde. PPE is usually not required for worker re-entry, a nd therefore these postapplication risk estimates are based on the baseline exposure scenario (i.e., typical work clothing but no gloves). Typically, the Agency
characterizes the risk estimate in relation to the restricted entry interval (REI) for a particular active ingredient. While REIs for specific product s are not discussed in this risk assessment, occupational post-application scen arios assessed result in MOEs that do not indicate risks of concern on Day 0 (the day of application).

Salicylaldehyde is expected to have high biologi cal oxygen demand, and it is expected to cause significant oxygen depletion in aquatic systems. It has a hi gh potential to affect aquatic organisms and the growth of some plants. It has a moderate potential to affect secondary waste treatment microorganisms and the ge rmination of some plants. This chemical is expected to be biodegradable and is not likely to bioconcentrate. The direct instan taneous discharge to a receiving body of water of an amount of this chemical which will rapidly produce, by dilution, a final concentration of 0.1 mg/L or less is not expected to cause an adverse environmental effect. After dilution with a large amount of water, followed by secondary waste treatment, this chemical is not expected to have any adverse environmental impact.

Salicylaldehyde has been tested for eco logical toxicity. Based on the studies, salicylaldehyde has the potential to affect aquatic organisms. The chemical is ready biodegradable and not expected to have advers e ecological effects due to dilu tion factor and biodegradability potential.

Salicylaldehyde is a naturally occurring ben zaldehyde found in food and is also used as a food additive. It is Generally Regarded as Safe (GRAS) with a human aver age daily intake of 16 ug/day and an annual natural occurrence in 66,47 0 kg of food per year. As a component of pesticides, up to 448 gm/acre of salicylaldehyde ma y be applied to a crop in a year. Based on the above toxicological data, potenti al residues of salicylaldehyde ar e unlikely to exceed the amount found naturally in foods and currently ingested.38 Appendix 1. Dietary Exposure Assessment

EPA Ver. 3.16, 03-08-d DEEM-FCID Chronic analysis for INERTS- SALICYLALDEHYDE NHANES 2003-2008 2-day Residue file name: J:\IN-10777\INERTS_57ACTIVE_100PPBH2OREV.R08 Adjustment factor #2 used. Analysis Date 10-09-2015/13:54:20 Residue file dated: 10-09-2015/13:53:41 Reference dose (RfD, Chronic) = .4 mg/kg bw/day COMMENT 1: Inert 57 active ingredients + drinking water (100ppb)

=============================================================================== Total exposure by population subgroup

-------------------------------------------------------------------------------

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- ---------------- Total US Population 0.053016 13.3% Hispanic 0.057893 14.5% Non-Hisp-White 0.052024 13.0% Non-Hisp-Black 0.049266 12.3% Non-Hisp-Other 0.062540 15.6% Nursing Infants 0.069497 17.4% Non-Nursing Infants 0.128725 32.2%

Female 13+ PREG 0.046267 11.6%
Children 1-6 0.153068 38.3%
Children 7-12 0.063675 15.9%

Male 13-19 0.037453 9.4%
Female 13-19/NP 0.038061 9.5%

Male 20+ 0.039479 9.9%
Female 20+/NP 0.042885 10.7%
Seniors 55+ 0.042752 10.7%

All Infants 0.110440 27.6%

Female 13-50 0.040993 10.2%
Children 1-2 0.197747 49.4%
Children 3-5 0.135978 34.0%
Children 6-12 0.070155 17.5%

Youth 13-19 0.037743 9.4%

Adults 20-49 0.040527 10.1%

Adults 50-99 0.042501 10.6%

Female 13-49 0.040973 10.2%

-------------------------------------------------------------------------------