UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: March 15, 2012 

OFFICE OF CHEMJCAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Prometon: Human Health Assessment Seeping Document in Support of 

Registration Review 

DP Barcode: D405084 

Registration No.: NA 

PC Code: 080804 

Decision No.: NA 

Petition No.: NA 

Risk Assessment Type: NA 

TXRNo.:NA 

MRIDNo.:NA 

Regulatory Action: Registration Review Seeping 

Case No.: 2545 

FROM: 

THRU: 

CAS No.: 1610-18-0 

40CFR: NA 

William Irwin, PhD, DABT, Toxicologist/Risk As 

Wade Britton, MPH, Industrial HygienQt 

William Donovan, PhD, Chemist 

Risk Assessment Branch V (RAB V) ' 

Health Effects Division (7509P) 

Office of Pesticide Programs 

Michael Acting Branch Metzger Chief, RAB V /J~j)~ 

Health Effects Division (7509PJ. ' a . ' 

Office of Pesticide Programs V 

b 

TO: Steven Snyderman/ Kaitlin Keller 

Risk Management and Implementation Branch III (RMIB III) 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs 
Prometon Human Health Scoping Document 0405084 

Executive Summary 

The HED Prometon Registration Review Team has evaluated the most recent human health 

assessments and database for the herbicide prometon to determine the scope of work necessary to 

support registration review for the chemical. The main non-occupational exposure is through 

drinking water. Registered uses of prometon are limited to non-agricultural areas including 

rights-of-way, military installations, recreational areas, airports, highway medians, lumber and 

industrial yards, railroads, guard rails, firebreaks, and pipelines. 

Prometon is a non-selective "bare-ground" herbicide labeled for pre- and post-emergence 

applications to manage annual and perennial grasses and broadleaf weeds in parking lots, 

roadsides and under pavement. Following use, all vegetation is typically killed resulting in a 

bare-ground patch where the herbicide was applied. Prometon is a photosynthetic inhibitor 

which acts by disrupting C02 fixation and production of intermediary energy components- ATP 

and NADPH. The most efficacious weed control method is through direct soil applications, 

which with sufficient water from rainfall or irrigation, allows prometon to readily move to the 

root systems. 

The exposure database for prometon has been reviewed and determined to be complete. Because 

prometon is a non-food/non-feed chemical, any potential dietary exposure is attributed only to 

drinking water sources. The most recent dietary assessment (drinking water only) conducted to 

support the 2008 Reregistration Eligibility Decision (RED) concluded that risks were below the 

level of concern. HED does not expect that a new dietary risk assessment will be needed for 

Registration Review. 

All occupational exposure scenarios previously assessed for workers applying prometon are not 

of concern at some level of personal protection. Occupational exposures to workers re-entering 

prometon treated areas are not anticipated because the chemical is used in non-agricultural areas, 

and there are no post-application activities required so that re-entry is unnecessary. No 

occupational exposure data gaps were identified during the Registration Review scoping process 

for prometon. Any changes in exposure assumptions, or update in prometon endpoint selection 

may require a revision of occupational exposures/risks. 

Residential exposure scenarios were evaluated previously, and 2 of the 7 residential handler 

scenarios assessed were determined to be of concern. Based on the risks of concern, the product 

registrant(s) agreed to voluntary cancellation of all residential uses of prometon. This 

agreement is detailed in the Prometon Reregistration Eligibility Decision (RED). On January 2, 

2012 the Agency published in the Federal Register (FR Vol. 78, No. 1) a notice of receipt of 

requests for an amendment to delete all residential uses of prometon on registered labels. 

However, these products continue to be available for residential use. If these uses are not 

withdrawn, an updated assessment of residential handler exposure may be required during 

registration review using the revised 2012 Residential Standard Operating Procedures (SOPs). 

The only data requirement is a 28-day inhalation toxicity study. 

Page 2 of 17 
Prometon Human Health Scoping Document 0405084 

In accordance with the Agency's 1986 Guideline for Carcinogen Risk Assessment, Prometon is 

classified as a Group D Chemical (Not Classifiable as to Human Carcinogenicity). Prometon was 

negative in the mutagenicity/ genetic toxicity studies including a bacterial mutagenicity (Ames 

test), rat micronucleus test and an unscheduled DNA synthesis test. Prometon is a di-N-alkyl 

methoxy triazine herbicide but because it did not demonstrate mammary gland tumors in 

Sprague-Dawley strain rats was not included in the common mechanisms model for the chlorotriazines that included atrazine, simazine and propazine (refer to the document entitled "The 

Grouping of a Series of Triazine Pesticides Based on a Common Mechanism of Toxicity" 

prepared by U.S. EPA Office of Pesticide Programs Health Effects Division. March 2002). The 

immunotoxicity study did not indicate toxicity to the immune system at the limit dose. 

There were no indications of increased susceptibility to the fetuses or neonatal animals in either 

the rat or rabbit developmental toxicity studies or the rat multi-generation reproduction study. 

A quantitative acute dietary risk assessment is not required since there were no acute toxicity 

endpoints of concern identified in the database, including the pre-natal studies in rats and rabbits. 

A chronic Reference Dose was derived from the NOAEL of 5 mg/kg/day established in the 

chronic dog study. The LOAEL of20 mg/kg/day was based on emesis and decreases in body 

weight/body weight gain. This dose and endpoint is supported by comparable findings in the 

two-year chronic study in rats and the two-generation reproduction study in rats. The 2 1-day 

dermal toxicity study in rabbits was selected for quantification of dermal risk. The LOAEL of 

500 mg/kg/day based on decreases in body weight and food consumption was selected as the risk 

assessment point of departure (POD) because a NOAEL was not established in that study. The 

Level of Concern (LOC) is a Margin of Exposure (MOE) of I ,000 which includes the 1 OX for 

inter-species extrapolation, 1 OX for intra-species variation and 1 OX UF for extrapolation from 

the LOAEL to an estimated NOAEL. An oral POD (NOAEL of 5 mg/kg/day) was selected for 

quantification of inhalation risk. The HASPOC determined that the use of an oral POD results in 

unacceptable MOE (190 for loaders and applicators) and that a sub-chronic inhalation toxicity 

study is required. Therefore the LOC for quantification of inhalation risk is an MOE of I ,000 

which includes the I OX for inter-species extrapolation, lOX for intra-species variation I OX 

uncertainty factor for the lack of a subchronic inhalation toxicity study (UFos). The PODs, 

endpoints of concern and the FQPA Safety Factor will be re-evaluated upon receipt of all studies. 

The toxicity profile and endpoints are presented in Tables A.2.1, A.2.2, and A.2.3 of the 

Attachments section of this document. 

Residue Chemistry 

Prometon is not currently registered as a pesticide for uses in food commodities; therefore, 

evaluation of residues in crops is not needed. 

Dietary Exposure 

Prometon is not currently registered for food-uses in agricultural commodities. Dietary 

exposures are limited to the potential presence of prometon in drinking water. The most recent 

dietary exposure analysis for prometon reported a maximum exposure level of0.016 mg/kg/day 

Page 4 of 17 
Prometon Human Health Scoping Document 0405084 

(33% cRfD) for All Infants(< 1 year old), based on a prometon water concentration of236 ppb 

for ground water (D3429031 W. Donovan, 9/04/2007). The estimated drinking water 

concentration (EDWC) of236 ppb was characterized by the Environmental Fate and Effects 

Division as being a high-end estimate (D335304, J. Hetrick, 7/3112007). As a result, HED does 

not expect to update the dietary exposure analysis in registration review, unless a new EDWC 

significantly higher than 236 ppb is provided. 

Residential Exposure 

Residential handler exposures were considered in the most recent residential risk assessment 

(0349797, W. Britton, 3/2008). Combined handler dermal and inhalation residential risk 

estimates were calculated using the Aggregate Risk Index (ARI). The ARI approach was 

required to combine the dermal and inhalation routes of exposure because of the different target 

levels of concern (LOCs). The majority of handler exposures assessed were not of concern to 

HED (i.e., ARls are ~1) . However, 2 of the 7 residential handler exposure scenarios identified 

were of concern and, as a result, the product registrant(s) agreed to voluntary cancellation of all 

residential uses of prometon. As mentioned, the notice of receipt to cancel residential uses was 

published January 2, 2012. 

Residential post-application exposure to prometon is not expected because HED does not 

anticipate significant dermal exposure from previously treated areas. Residential use of 

prometon is limited by current labeling to areas where no plant growth ·is desired and dermal 

contact with these areas is assumed to be limited. Current labeling recommends that granular 

and liquid fonnulations of prometon be watered-in to be effective. This practice causes 

prometon to move into the root zone of the soil, further reducing the potential for postapplication exposure. 

Conclusion. No residential exposure data gaps were identified during the Registration Review 

process for prometon. While the product registrant(s) agreed to voluntary cancellation of all 

residential uses of prometon and a notice of receipt of requests for an amendment to delete all 

residential uses of prometon on registered labels was published in the Federal Register, these 

products continue to be available for residential use. If these uses are not withdrawn, an updated 

assessment of residential handler exposure may be required during registration review using the 

revised 2012 Residential Standard Operating Procedures (SOPs). 

Drinking Water Assessment 

The previous assessment recommended a conservative chronic EDWC of236 ppb (J. Hetrick, 

0335304, 7/3 1/2007). Should a higher value be recommended during registration review, then 

HED will re-evaluate the dietary assessment (water only) based on this information. 

Aggregate Risk Assessment 

Assuming all residential uses are cancelled, no acute, short-, or intermediate-term exposure 

scenarios exist for prometon; the only non-occupational exposure scenario is the chronic dietary 

exposure from drinking water, which comprises the aggregate exposure for this chemical. As 

Page 5 of 17 
Prometon Human Health Scoping Document 0405084 

previously discussed, there are no risk concerns for chronic drinking water exposure; therefore, 

there are no aggregate risk concerns. 

Occupational Exposure 

Due to the manner in which prometon is used, occupational exposures are anticipated for those 

involved in the application process (i.e., mixers/loaders, applicators, and 

mixer/loader/applicators). Occupational exposures to workers re-entering prometon treated areas 

are not anticipated because the chemical is used in non-agricultural areas, and there are no postapplication activities required so that re-entry is unnecessary. 

Prometon containing products are formulated as emulsifiable concentrates, flowable 

concentrates, granulars, and ready-to-use. Applications of prometon can be made by ground 

using ground boom, rights-of-way, tractor drawn spreader, and hand-held spray equipment. 

Product application rates range from 8 to 18 lbs ai/ A, or 0.41 lb ai/1 ,000 e. Based upon the use 

pattern of prometon, HED anticipates both short- (1 to 30 days) and intermediate-term (1 to 6 

months) occupational exposures. Long-term handler exposures (greater than 6 months) are not 

expected to occur. 

Occupational handler exposures for all formulations were considered in the most recent 

occupational risk assessment (D349797, W. Britton, 3/2008). All handler exposure scenarios 

assessed (dermal and inhalation combined) resulted in margins ARis 2:. 1 at some level of 

personal protection and, therefore, were not of concern. 

Conclusions. No occupational exposure data gaps were identified during the Registration 

Review seeping process for prometon. Further, there are no significant changes identified which 

would require an update of the occupational exposure risk assessment. A task force effort by the 

Agricultural Handlers Exposure Task Force (AHETF) may provide improved exposure data 

relative to that in the Pesticide Handlers Exposure Database (PHED) and the Outdoor Residential 

Exposure Task Force (ORETF), which were used previously to assess occupational risks. Any 

impact to exposure data, or update in prometon endpoint selection may require a revision of the 

prior assessments to reflect these changes. 

Public Health and Pesticide Epidemiology Data 

For the Main IDS (higher severity human outcomes), from January 1, 2007 to September 13, 

2012, there were 26 incidents reported for prometon for single chemical only in the database and 

3 additional incidents reported involving more than one chemical. One incident was classified as 

major severity which involved a worker entering a greenhouse 2 days after it was treated and 

developing anaphylactic shock requiring treatment in an emergency room; the other incidents 

were classified as moderate severity. Overall, there are few incidents involving prometon 

reported to IDS. In Aggregate IDS (less severe human incidents), from January l, 2007 to 

September 13, 2012, there were 106 reported incidents involving prometon. 

In SENSOR-Pesticides from 1998 to 20081 40 cases (from 34 events) involving prometon 

exposure were identified. Prometon is listed as the sole active ingredient in 25 of the 40 cases. 

Page 6 of 17 
Prometon Human Health Scoping Document D405084 

Twenty cases are classified as work-related. A review of case narratives identifies pesticide 

handling (mixing, loading or applying) as the activity at the time of case exposure in 22 (of 40) 

cases. Of the 22 work-related cases, 12 were due to handling activities and ten non work-related 

cases were applying the herbicide residentially. Of the 40 cases, six cases are moderate in 

severity' and 34 are low in severity. Symptoms for the six moderate severity cases varied widely 

and included altered taste, wheezing, pneumonia, and headache. Two moderate severity cases 

reported major respiratory symptoms. One case reported "pneumonia, cough and shortness of 

breath." The second moderate severity case with respiratory symptoms went to the ER and his 

case report stated "Patient is cyanotic looking around lips, 0 2 of92%. Wheezing throughout 

lungs, c/o chest pain. " Respiratory symptoms are the most commonly reported health effect, 

followed by symptoms related to the nervous system, gastrointestinal, eye and dermal effects. 

There was one incident classified as major severity (further described in Table 1 in the incidents 

report, D406960). However; it is not clear that this incident is related to prometon or the 

implicated product (Ground Clear Triox Total Vegetation Killer). The individual developed 

anaphylactic shock five hours following exposure in a greenhouse that had been treated 2 days 

prior, suggesting that the incident was not related to the product. In addition, the implicated 

product, Ground Clear Triox Total Vegetation Killer, is intended for outdoor use as a total 

vegetation killer, and not likely used in a greenhouse (i.e. not a registered use site). Also it is 

very likely that multiple pesticide products were used in the greenhouse. It is important to note 

that, reports submitted to the IDS are un-substantiated; they represent anecdotal reports or 

allegations only. 

Based on the low frequency and severity of incident cases reported for prometon in both IDS and 

NIOSH SENSOR, there does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in the risk assessment. 

Tolerance Assessment and International Harmonization 

Tolerances are not established for prometon since no registered pesticide uses in food 

commodities exist at this time. No Codex maximum residue limits (MRLs) have been 

established for prometon. Therefore, there are no international harmonization issues. 

Environmental Justice 

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec order 12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, and the variability of 

diets within the U.S .. Should these highest exposures indicate potential risks of concern, OPP 

Page 7 of 17 
Prometon Human Hea lth Scoping Document 

further refines the risk assessments to ensure that the risk estimates are based on the best 

available information. 

Cumulative 

0405084 

Prometon has not been identified as a member of a common mechanism group. Although 

prometon is a triazine chemical, it is specifically a methoxy triazine and not included in the 

common mechanism group or cumulative assessment group for the chloro-triazines. A common 

mechanism of toxicity has not been demonstrated for prometon with the other triazine 

compounds. Furthermore, prometon does not produce the DACT (diaminochlorotriazine) 

metabolite common to the members of the chloro-triazine cumulative assessment group. 

Human Studies 

Prometon risk assessments rely in part on exposure data (i.e., PHED and ORETF) from studies in 

which adult human subjects were intentionally exposed to a pesticide or other chemical. These 

studies have been determined to require a review of their ethical conduct, and have received that 

review. 

Endocrine Disruption 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision, EPA reviewed these data and 

selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), prometon is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Page 8 of 17 
Prometon Human Health Scoping Document D405084 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients artd 9 inert ingredients. Prometon is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for prometon. For further information 

on the status ofthe EDSP, the policies and procedures, the list of67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Data Requirements 

The 28-day inhalation study (870.3465) is required. 

References 

Author Barcode Date Title 

W. Donovan D349795 3/ 17/2008 Prometon: HED Chapter of the Reregistration Eligibility 

Decision Document (RED). Phase 4 Revisions. 

J. Hetrick D335304 7/31/2007 Drinking Water Assessment for Uses of Prometon 

J. VanAlstine TXR# I 0/25/2012 Prometon: Summary of Hazard and Science Policy 

0056500 Council (HASPOC) Meeting of October 25, 2012 

S. Recore D406960 10/ 15/2012 Prometon: Review of Human Incidents 

Kristen Knox NA I 0/3/2012 Prometon Residential Uses 

(MANA) 

Page 9 of 17 
Pr In to u=m=a=n~H~e=a=lt=h~S=co~p~in~g~D==oc=u=m=e=nt ________________________________ D~4 05084 

Attachments 

A.l Chemical Identity 

Table A.l.l Chemical Identity of Prometon. 

H CH3 I I 

H3C-O"-.. -~:N " / N-CH- CH3 

r rrStructure ~ ,.N T/ 

References: K. Dockter, 

H/N· '· c~l --CH 3 17-JAN-1985 

I 

CH And 

3 

The Pesticide Manual: N2,N 4-diisopropyl-6-methoxy-1 ,3 ,5- IUPAC Name A World Compendium, triazine-2, 4-diamine 7th ed., 1983, C.R. 

CAS Name 6-methoxy-N,N'-bis(l-methylethyl)-1 ,3,5- Worthington, ed. The 

triazine-2,4'-diamine British Crop Protection 

Common Name Prometon Council, Croydon, 

Molecular Formula C10H19N50 England, pg. 695. 

Molecular Weight 225 g/mole 

CAS Registry Number 1610-18-0 

PC Code Number 080804 

Physical State Colorless powder 

Melting Point 91-92°C 

Solubility (20°C) 620 ppm in water 

Log Kow (20°C) 4.3 

Page 10 of 17 
Prometon Human Health Scoping Document 0405084 

A.2 Toxicity Profiles and Endpoints 

Table ..\.2.1 Acute Ton city Profile - Prometon 

GUtdehneNo Srudy Type ~fRID(s) Results Tox.icuy Category 

370.11 00 Acute oral - rat 42132103 LDso= 4 345mg'kg m 

for males and 

15 18 mglkg for 

female<>. 

870.1200 Acute dermal - rabbit 4160911 2 >2020 mglkg m 

870.1300 Acute inhalation- rat 42132 104 LC'sQ = .. > ll 

0.52mgll.. 

870.2400 Acute eye irritation - rabbit 42144601 ConJunctivae m 

redness :md 

chemosis and 

discharge 

regres<.>ing by day 

7 

870.2500 Acute dermal irritation - rabb1t 41609113 Avery slight I\t 

erythema cleared 

by 24 hours 

870 2600 Skin semitization - guinea pig 41609114 Not a sensitizer --

The acute studies were rt•\·iewed by Marianne Lewis . Product Regi<.>tr.~tion Branch_ Special Re,·iew and 

ReR.eg~ tr ion Division (7509?). Refer to memos dated July 18. 2007 (primary eye and derm.1l irritation and 

derll131 sensitization) ;md July 20. 2007 (derm.1l toxicity). The dermal sensttization study was determined to be 

unacceptable but .. based on information found in the study and the open literature. the Agency will classify the 

techmcal as a non eusuizer. A new srudy is not needed ... 

Page 11 of 17 
Prometon Human Health Scoping Document 0405084 

lnblt :\ .:.: '.lubclu ir~ Clu ouk and Ollm Tollcity P1 ofile for Pa omttou 

Cll.ldt.lule Snul:, T~-pf ~!RID :-o. (yt~rJ Rt:ulll 

:"io. Ch-:ifit'ltiou Do:r 

s-oJ lOO 90-Day or.ll 00!299S.S (!981) ~O~.EL = 5 ~lt~ dty 

!Oal:CLIY - rn .ful= LOAEL .. I.> tDJ1t: dly b.iad Clll ktdluy "''~ :mG 

kldney wegbt rob~ ratw. 

0, 05.15. 5- or 15 

c::k~.Uy s~ ~...0 lbr dlt-o::i-t n t :m..ry. 

S70.5150 90-Dl"' c.~ l ::wH tn cl:ron:c !?edl!:g mJd:y be:!m\·. 

tanury · ~ 

$70 l~OO 21 D•:.-~ .t21~2 l~S7) NOAEI. •15a:~~'k."cby 

to:ci-city (nbhtt) A«'.,w.bJ. <7t.udotlwe lOAEL = 500 cg 'k~ da.y bs:.ed on~ body \\-ei~ 

mcll'= md rood =~'OI!l m £ea:.tlu. 

0. 25, ~Oor 10)0 

q\phr 

a·o 3~so 90-Ihy~ ~o ~l"'dy n'Zil:ll:U JJ:Id DOl nqurtel 

ta:a.~in- ( ::;pecte>) 

s-o.>-+6.5 ay uilia!.a.t:cr. ~0 ~hldy anJ.lab~~ but woc:!d b.e ~qu:md If there \\'eft ~l~C.ml rnha!atlac ~ 

to:ID.U.") (;~> 

o roo.\ Plu.u..J 00129983 OOl.;s6C-9 ad ~l 1rtna::t i NO.iUl. "' .)6 =r'lc~Y 

.w.~ in 211~90 9S~ ) LO . .:..EL = 110 :::1g q 'day ba.:.ed on ~e=•~ ~'a:lOU z::,d 

·~ ~11n1:::;um chrocaoJt=on:bu. 

Den.lopiJmltal O. = 360mgkg:-da:: (H!J.), LOAE.. 

0. 36. no or J60 oot~ubC::.bt<i 

r,e:'k~day 

s-orOOb Prauta.l 00Jl99S4. 00l-*S609 r.d ~hrerual NO = 3.5 mg'k_g. d;r,• 

dn"tl~ in. 9~ 149'J08 (1981 LOA.EL., 24 5 ~''d..wbued Clll~Oody .- ~ 

1-iliba l;.ll.ulmwn ;;.nd ~ '"C.5ht mau:.e in la.c1i::::ati~ and an=-~ 

Dt-\"tlop mt11 t'll J.;OAl!l. •24 5 me ks·'~· (HDT). LOAE!.. 

o, 0.5, 35 Ql' 24 5 no ~.tlb~ 

~'lc~day 

t703SOO F....p1 CIGclloD. mli ~~36151 9 (l9S7) Plln!lll<tl ~~-:.tttait' ~OAEI.. • 14.5 ~·k(oily 

t"L"tlluy effe= G-..Uc!e!me 

LOAEI... = 35.00. m;:ikglday b~ o::t ~body 

mrm ~L!in m DDlt=. m both~~ ci!Kre.-d f* 

0, 20, 500or )C{}~PIP con::ll:llpti:c.D i:l ::.n.1.le~ in. :~co:d ~i!llSatl'c::. 

( ~.:;tw::a:ted 0. l. 4 5. 3 S.DS Rt-productiH NOAEL ,.. P.<to .ad-1-ene effKt~ ce 

Dd {(;3 96tz<J lrr t.bv ~-~pufovm:;.nc-e] 

fur :u:u!c 3Ild 0. !.59. Off;p~~o.~ = 1..59 ~ kg'd.i;;- (IIJ.l!enW) 

3~ l7GJ HHS I .. W. "' .>9 1" UJW 6v 'b;.:.4d ® ciw"e.r.eQ Y'IP V>llt~ 

~'k.g dJy <>r~) dun::.r ~acunce penod m ~ond gt!lel-atlD.Il ill both 

c:ez:oa-:tngc;· at c. mf,ber O:l:.e 

Page 12 of 17 
Prorneton Human Health Scoping Document 0 405084 

Tablt A.~.1 Subdn onic. Clm:mtc aud Orhtr oxk ~· Profile !or Promtton 

G~tid .lint '"'~ ~lH IKID ~o. ~ •~11 Rt~ul J 

~o. C ~::rfiution Do:.~-: 

s-o . .uooa Cl:romc Wlllctly 4()1SS l 02 {l9SS \ ~OAfl. 'J.S~ a US)~'k~ cay 

r.n Guidtlme LOA.fl. .. :l3 3(01 l 2) q'q d:i)' b~~edon <l"Ft~:ed 

me.m body"'~ md ~Ill Wmi.r.. 

0. 0 89 .Jor 71 "'I few 

= le:. =dO. US. 31.2 

O'l l 01 5 Col !&!~.We~ 

~k d:ay. 

Sil·HOOb Cbrouu: taxJClly .;oo9"'90 1 a:;d i:Olt..El.. ... 5 ~'k~ day 

do; .;~6581 l (19S6) lOAEl."' :!0 a:; 'k; chy b:t-:ed on deprl.'~-:i= cf'bodv 

Muu_""= \ni.Pl md a cloH reWed~ :n ~ ID both~. 

a. 5, ..:o 3Dd so 

=:'kr·d.:ty 

s-J o~~oo ttm~~ ~SS102 (19SS) Refer to cl:-omc to::acny abo;·e fM 'SOAEI.. and LO.!,EL 

and c:arcno~c:;ty C"1llde!me rat :\o n idf!U'tt of .udno .ni<it . No..-.- c;wuw.~ 

Q_ 0.89. 23.3or 73.7 fOI' .dmoma:.. ~arcooe.r. d fibra:na:; ';t;l!Ie v.'ltb 

m.al~ md 0. llS, 31:! b.: ton~alt*ll,,.. 

Ol' !0.2.5 or~ 

~'q cby. 

s-o .:JOO c ..... ·c:inop-ru.em• -3().;88 HH (!9SS) );OAEL = 70 ~·'k"&y 

~e} G-u.i ~ LOA.EL = ., nm.~'l!'day~ on ~wn"i\~ 

(mat....). ~-~ boCv '-l"f!i~ pie 6 both~. OC'll· 

0. ·-2. "0, 737 ar-147..: ceopwtlc !nv ~n,~ (CL"uW ~am-::uum. ~ a!1 

~··d;;y ~toey

~ 

;t n.ecnr.h .;:.d c~le cellbt-p~ o-.~ Qt'O'O~ ~ 

~oWlu!Rhypemopby, 

::'\o n-ld enre of carcillogtmcirr 

~ 8actm.ali11W:all0n ~36-401 (i9SS) ~~of» tnl~J4mk tf!kt u =.~ ~ fbcm w 

1'-i'u :~.t:o (A.c.:lot1 tr.:t) ~ctptiblt ~l) ;abtta~t~ella ~ln= TA10 .. TAI535, TA15} i ,orTA t53S 

s-()5100 ~'lth or ~'lthcut a:e.ubohc u1l\~ 

0, .25, 100, 500, 1000 01' 

2500 jl~'p!.m 

Cyto~ R.JJ m;.(.TOillUCJ.tu~ -l063~1 m:i 419S4J01 ~ "~o " om:re= lil«t io!lowq 64$ ~ q wd 

S"''5 :!95 td (i9SS)_ sac:ri:frce at 16. 24 or ~ hom:;. 

Attept3llle. (009&02) 

648 qltl hl:ba~ do. 

t~ed. 

--

Page 13 of 17 
Prometon Human Hea lth Scoping Document 0 405084 

T:.tbl~ ~ :Subdu omc. C lu oulc 3nd Othu T ... ~cm Pt ofilt fox Pt omtton 

C.wd' t <.tull T)pt lf'RID :"o () f" f! Rgulll ~-0 Ch7:ifi.-.,non Do:t· 

Other Uc.:~dO A 4363&+33. 4 l9S4303 .=! ~ tnd:.allnn of=.d:e~ule=: O:tA Tej)m. 

Effe.:t• 'UI!M·a · -t:JlS10J (19S} s<J ss;o I 

A~~!e (CC9Sv:) 

0. : 10 50. : .:xJ 200 Of 

.;,, u;ml 

·-~ 6100a Acu:. DIWoto:DCUY 

~cr~m; :::,Jt"An' 

s-o 6:CM> Subchroc.:-:: 

nmavtcncKtty };o ·~~ ~--uhh£. ~Dd uot ~ 

~cnenin: b.1 Itt:)' 

s--o 6300 iR-'>~.enb.l 

ll82010100fy 

"-J ""i )\fa ~~~~ ~.;0 ·-..!'· l\' ~bt. 

P~= 

pear. 

""') 7600 Dc:W 

~L 

trr:lOC , • 0 •nact- lV~b!- ~-l,..ufeG f« pc~ 

SpeC'ul 1W':e ~ 

Table A.2.3 Summary of Toxicological Doses and Endpoints for Prometon for 

Use in Dietary, Occupational, and Residential Human Health Risk Assessments 

RfD, Level of 

Exposure/ Point of Uncenainty Concern for Study and Toxicological Effects Scenario Departure Factors Risk 

Assessment 

Acute 

Dietary 

(General 

Population, 

including 

Infants and No relevant toxicity endpoint for a single dose exposure was identified. Children) 

Acute 

Dietary 

(Females 

13-49 years 

of age) 

Page 14 of 17 
Prometon Human Health Scoping Document 0405084 

Table A.2.3 Summary of Toxicological Doses and Endpoints for Prometon for 

Use in Dietary, Occupational, and Residential Human Health Risk Assessments 

RID, Level of 

Exposure/ Point of Uncertainty Concern for Study and Toxicological Effects Scenario Departure Factors Risk 

Assessment 

Chronic study with dogs: 

NOAEL=5 mglkg/day 

LOAEL = 20 mg/kg/day based 

on emesis and body weight 

effects. The other co-critical 

studies were the chronic rat and 

the two-generation rat 

reproduction studies. 

Chronic Rat Study: 

NOAEL = 0.89 (or 1.18) 

mg/kg/day 

LOAEL = 23.3 (or 31.2) 

mg/kg/day based on depressed 

mean body weight and gains in 

fema les. 

Chronic NOAEL=5 UFA= lO x Chronic RfD = Two-General ion Reproduction 

Dietary (All mglkg/day UFH=!Ox 0.05 Study: 

Populations) mglkg/day Parental/Systemic NOAEL = 

1.45 mglkg/day 

LOAEL = 35.08 mglkg/day 

based on decreased body weight 

in males in both generations and 

decreased food consumption in 

males in second generation. 

Reproductive NOAEL = [No 

adverse effects on reproductive 

performance) 

Offspring NOAEL = 1.59 

mg/kg/day (maternal) 

LOAEL = 39.17 mg/kglday 

based on decreased pup weight 

during lactation period in second 

generation in both generations at 

the higher dose. 

Page 15 of 17 
Prometon Human Health Scoping Document 0 405084 

Table A.2.3 Summary of Toxicological Doses and Endpoints for Prometon for 

Use in Dietary, Occupational, and Residential Human Health Risk Assessments 

RID, Level of 

Exposure/ Point of Uncertainty Concern for Study and Toxicological Effects Scenario Departure Factors Risk 

Assessment 

Chronic study with dogs: 

NOAEL=5 mglkg/day 

LOAEL = 20 mglkg/day based 

on emesis and body weight 

effects. The other co-critical 

studies were the chronic rat and 

the two-generation rat 

reproduction studies. 

Chronic Rat Study: 

NOAEL = 0.89 (or 1.18) 

mg/kg/day 

LOAEL = 23.3 (or 31.2) 

mg/kg/day based on depressed 

mean body weight and gains in 

females. 

Incidental 

Oral Short NOAEL=5 UFA= IOx Two-Generation Reproduction 

and mg/kg/day UFH= 10x 100 Study: 

intermediate Parental/Systemic NOAEL = term 1.45 mg/kglday 

LOAEL = 35.08 mglkg/day 

based on decreased body weight 

in males in both generations and 

decreased food consumption in 

males in second generation. 

Reproductive NOAEL = [No 

adverse effects on reproductive 

performance] 

Offspring NOAEL = 1.59 

mglkg/day (maternal) 

LOAEL = 39.17 mg/kg/day 

based on decreased pup weight 

during lactation period in second 

generation in both generations at 

the higher dose. 

Dermal 21-day dermal toxicity study in 

Short-Term LOAEL= UFA= IOx rabbits with a LOAEL of 500 

and 500 UFH= IOx 1,000 mglkg/day based on decreased 

intermediate mglkg/day UFL!Ox body weight and food 

consumption in females. 

Page 16 of 17 
Prometon Human Health Scoping Document 0405084 

Table A.2.3 Summary of Toxicological Doses and Endpoints for Prometon for 

Use in Dietary, Occupational, and Residential Human Health Risk Assessments 

RID, Level of 

Exposure/ Point of Uncertainty Concern for Study and Toxicological Effects Scenario Departure Factors Risk 

Assessment 

Chronic study with dogs: 

NOAEL=5 mg/kglday 

LOAEL = 20 mglkglday based 

on emesis and body weight 

effects. The other co-critical 

studies were the chronic rat and 

the two-generation rat 

reproduction studies. 

Chronic Rat Study: 

NOAEL = 0.89 (or 1.18) 

mg/kglday 

LOAEL = 23.3 (or 31.2) 

mglkglday based on depressed 

mean body weight and gains in 

females. 

Inhalation - NOAEL= 5 UFA= IOx Two-Generation Reproduction 

all durations mglkglday UFw:IOx 1,000 Study: 

UFoa= IOx Parental/Systemic NOAEL = 

1.45 mglkglday 

LOAEL = 35.08 mglkglday 

based on decreased body weight 

in males in both generations and 

decreased food consumption in 

males in second generation. 

Reproductive NOAEL = (No 

adverse effects on reproductive 

performance) 

Offspring NOAEL = I .59 

mg/kglday (maternal) 

LOAEL = 39.17 mglkglday 

based on decreased pup weight 

during lactation period in second 

generation in both generations at 

the higher dose. 

Cancer Classification: Group D--Not Classifiable as to Human Carcinogenicity (oral, 

dermal, 

inhalation) 

UF = uncertatnty factor. UF A= extrapolatiOn from am mal to human (mtraspec1es). UF B = potennal 

variation in sensitivity among members of the human population (interspecies). UFL =use of the LOAEL, 

instead of a NOA EL, for endpoint selection. 

Page 17 of 17