### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C . 20460 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM 

### D ate: April 9, 2014 

## SUBJECT: Dipropy l Isocinchomeronate (MGK-326): Tier I R ev iew of Human Incidents
P C Co de : 047201 OP Ba r co de: 0419 225 Decision No.: 489507 Petit ion No. : NA Ri s k Assess men t Type: NA TXR No.: NA 

### MRID No.: NA Regi s t ratio n No.: NA Regulatory Actio n : NA Case No.: NA CAS No.: 1 36-45-8 , 3737 -22-2 40CFR: NA 

## FROM: Shanna Recore , Industrial Hygienist Toxicology and Ep idemiology Branch Health Effect Divis i on (7509P) Ver.Apr
. 08



### and

# ~ E lizabeth Evans, Environmental Protection Specia li st**~**

### _**.~** 

### Toxicology and Epidemiology Branc h 

## v-Cf" Health Eff ects Division (7509P) 

# /J :j}
THROUGH: David Miller , Act ing Branch Chief 

# 1\__p , )

# f}tp~~**~** Toxicology and Epi demiol ogy Branch {)';..1o 1 

### Health Effect s Division (7509 P) TO : Thurston Morton, Risk Assessor Risk Assessment Branch IV Health Effects Division (7509 P) and Mo!Jy Clayton, Chemical Review Manager Risk Management & 

### Imp lementation Branch 3 Pesticide Re- eval uation Division (7508P) Summary and Co nclusions Based on the low severity of incident cases reported for diprop yl isocinchomeronate 

### in both IDS and SENSOR-Pestic ides, there does no t appear to be a concern at this time that woul d warrant further investigation. Th e Agency w ill continue to monitor the incident inform at ion and if a concern is triggered , additional analysis will be included in t he risk assessment.
Page 1 of 10

### Detailed Re v ie w 

## I. ACTION REQUESTED This rev iew is intended to fulfill our requir ement to docket summaries of in cident data that were reported to the Agency , as well as to ensure human incident data and the Agricultural Health Study (AHS ) are part of the probl em formu lation phase of registration review. Reports of adverse health ef fects allegedly due to a specific pesticide exposure (i
. e. , an " incident") are largely self

- reported and therefore, generally speaking, neither exposure to a pesticide or r eporte d symptom (or the connection between the two) is validated or otherw ise confirmed. Typically, causati on cannot be determined based on incident data. However , incident information can be an important source of feedback to the Agency : incide nt s of severe outcome , o r a s uggested pattern or trend among less severe incidents , can signal th e Agency to further investigate a particular chemical or product. Observational epidemiology studie s relate the ri sk of disease, 

## e. g., cancer , and exposure to an agent such as a pesticide product in the general population or specific sub-group s like pe st i c ide app li cator s . 

## II. BACKGROUND Dipropyl isocinchomeronate is an ins ect repellent. It is never used as the sole active ingredient (a.i). Rather, it is us ed to expand the spectrum of repellency of other formulation components. Dipropy l isocincho m ero nate can be appli e d to cats (adults/kittens) , dogs/canines (adult s /puppies) , human body/ clothing, horses (not intended for foo d ) , pet liv i ng/sleep ing quarter s. 1 

### Fo r this evaluation , both the OPP Incident D ata System (ID S) and th e Center s for Di sease Contro l and Preventi on/Natio nal Institute for Occupat ional Safety and Health (CDC/NIOSH) Se ntin el E vent No tific ati on System for Occup at ional Risk-Pesticides (SENSOR) databases were consu lted for pesticide inc ident data on the active ingre dient dipropyl isocinchomeronate (pc code: 047201). The purp ose of the database search is to identify potential patterns in the frequency and se v e rity of the health effects attributed to di propyl i socinchomeronate exposure. Dipropyl isocinchomeronate i s not included in th e AHS, and therefore t hi s stu dy does not provide information for this report. 

## III. RESULTS/DISCUSSION
a. IDS (Incident Data System) OPP's IDS includes reports of alleged human health incidents from various so urces , includi ng mandatory Federal In sec ti c id e , Fungicide and Rodenticide Act (FIFRA) Section 6(a)(2) repo rts from registrants, other federa l and state health and environmental agencies, and individual consumers. Since 1 992, O PP has compiled these reports in IDS. ID S contains reports from across the U.S. and most incidents ha ve alJ relevant product i nfo rm ation recorded. Reports

1 

### http :// www.epa.gov/oppOOOO I /chem

_ se arc h/reg

_actions/ reregistrationlred

_ P C

- 04 720 1

_23-Sep-03.pdf


### Page 2 of 10

### submitted to the IDS represent anecdotal reports or allegations only, unJess otherwise stated in the report. IDS records incidents in one oftwo modul es: Main IDS and Aggregate IDS:


### o Main ID S contains incidents resulting in higher severity outcomes and provides more detail with regard to case specifics. This system stores incident data for death, major and moderate incidents, and it includes information about the location , date and nature of the incident. Main IDS incidents involving only one active ingredient (as opposed to pesticide products with multiple active ingredients) are considered to provide more certain information about the potential effects of exposure from the pesticide.


## o Aggregate IDS contains incidents resulting in le ss severe human incidents (minor, unknown , or no effects outcomes). These are reported by registrants only as counts in what are aggregate summaries. As previously stated, dipropyl isocinchomeronate is never used as 

### the sole active ingredient and is always co-formulat e d in pesticide products. As expected, for the Main IDS , from January 1 , 2009 to March 5, 2014, there were no incidents reported for single chemical only in the database. There were 26 incidents reported involving more than one chemical. Twenty five incidents were classified as moderate sever ity. Of these, two incidents were suicide attempts and one incident was a duplication. One in c ident was classified as major severity. A 54 year old female got less than 1 

### tsp
. of the product on her hand while transferring the product from a refill bottle into a spray bottle. She experienced an allergic reaction. The remaining narratives are summarized in Appendix 

### 1. In Aggregate IDS , from January 1, 2009 to March 5, 2014, there were 449 incidents reported involving dipropyl isocinchomeronate. One hundred seventy nine incidents were classified as unknown or no effects and 270 incidents were classified as minor severity. Most (95%) of the incidents reported to IDS involving dipropyl isocinchome ronate were either minor severity (n=2 70) or no or unknown effects (n=179). For the minor incidents, this means that a person alleged or exhibited some symptoms, but they were minimally traumatic , the sy mptoms resolved rapidl y and usually involved s kin, eye or respiratory irritation. For the no/unknown effects , this mean that symptoms are unknown , unspecified or are alleged to be of delayed or chronic nature that may appear in the future. The most often implicated product in both Main and Aggregate IDS is Reg. No. 270-343 (Adams F lea and Tic k Mist). In ad dition to containing 0.5 % dipropyl isocinchome ronate, this product also contains pyrethrin s (0.15%), piperonyl butox ide (1.50%) and n-octyJ bicycloheptene dicarboximide (0.5%). It 

### was implicated in 73% of the dipropyl isocinchomeronate incidents reported to IDS. This may be potentially attributable to high use of this product by consumer s . Obtaining additional information on current u sage data for dipropyl i socinc homeronate woul d 

## improve future assessments. Adams Flea and Tick Mist is used by 

## homeo wn e rs on horses, dogs, puppies, cats, and kittens to kill fleas, ti cks, and lice and to repel flies , gnat, and mosquitoes.
Page 3 of 10

### This product label instructs users to rub the product i n to pets' fur with their hands leading to dermal exposure. 

## b. SENSOR

-Pesticides The SENSOR-Pesticides database covers 1 1 states from 1998

- 2010, alth ough reporting varies from state to st ate. Cases of pesticide-related illnesses are ascertained from a variety of sources, includi ng: reports from local Poison Control Centers, state Department of Labor workers' compensation claims when reported by physicians, reports from State Departments of Agricu lture, and physician reports to state Departments of Health. Although both occupati onal and non-occupati onal incidents are included in the database, SENSOR-Pesti c i des focuses on occupational pes ticide incidents, and is of particular value in providing that information. The state coordinator at each of the 1 1 respective state Departments of Health conducts case fo ll owup activities such as obtaining medical records to verify symptoms and sever i ty
. Using standardi zed protocol and case defin itions derived from po i son center reporting, the state SENSOR-Pesticide coordinator enters the incident information into the state-based system whi ch is sent to NIOSH annually to be aggregated. A query of SENSOR-Pesticides from 1 998

- 2010 identifies 73 cases involv ing dipropyl isocinchomeronate (pc code 04720 1). All cases involve multiple active ingredients
. Only 8 cases were work

- re l ated, 40 cases were not work

- related and 25 cases were unknown with regards to whether or not it was work-related. Cases involved either insect repellents or flea/tick pe t products. Thirty two cases involved children under age 1 2. Twenty of these cases invo lved the child getting the product sprayed in their face/eye. Two cases were high in severity, three cases were moderate in severity, and 68 cases were low i n severity. One high severity case involved intentional ingestion of the product and the second high severity incident i nvolved application to open wounds. The high and moderate severity cases are summarized in Tablel
. Table 1. SE NSOR-Pesticides 1998-2010 

### High & 

### Moderate Dipropyl Isoincbomeronate Case Descriotion s 

## m 

# I Severit y 

# I Year 

# I Case Description NY00695
F L00261 TXOI609 OROI1 1 5 NM00022 High High Moderate Moderate Moderate 2003 1998 1999 2004 2005 According to chart, mother reports patient ingested unknown
. amount of Wellbutrin and Wipe On for horses insecticide. Complainant had fire ant bites on his legs when he applied product. Open wounds provided direct route of entry to bloodstream Case licked arms that had insect spray on them. Later mother noticed case had twitchin g o f eye and neck muscles. Closed container over pressurized in aircraft resulting in exposure to pilot Cas e reported that he was sprayed wi th fly

- foil spray when fly

- foil spray was being applied to a truck full of onions. 

### Route of Exposure and Symptoms The most common route of exposure reported was ocu lar (n =41); fo ll owed by dermal (n=26)
. The symptoms reported reflects this as well with ocular symptoms (such as redness and irritation) being the most common (n =44) fo ll owed by dermal symptoms (n=22). A summary of symptoms reported is prov i ded in Table 2. Page 4 of 10

### Table 2
. SENSOR-Pesticides 1 998 -2010: Reported Health Effects for Dipropy l l so inchomeronate N=73
Health Effect # of Times Reported Dermal 

### 22 Ocu lar 

### 44 Respiratory 13 

### Gastrointestinal 10 Renal 

### 0 Nervous System 13 Cardiovascular I 

## * Case-S may repon mu lt iple h ea lth effects



### c. Agricultural Health Study (AHS) 

### The AHS is a high quality , prospective epidemiology s tudy evaluatin g the link between pesticide u se and various health outcomes including cancer. The AHS includes private and commercial pesticide applicators and their spouses. Ifth ere are AHS findings relevan t to a particular pesticide going thro ugh reg istration review, th e Agency will ensure th ey are considered 

### in the problem fo rmulatio n/scoping phase of the proce ss and, if appropriate , fully reviewed in the ri s k assess ment phase of the p rocess . The AHS in c ludes information on u se of 50 different pesticide active ingredients commonly used in agriculture. Dipropyl isocinchomeronate is not included in the AHS, and therefore this study does not provide information for this report. 

## IV. CONCLUSION 

### Based on the low sever ity of in cident cases reported for dipropyl isocinchomeronate in 

### both IDS and SENSO R-P esti cides, there does no t appear to be a concern at this ti me that would warrant further investigati on . The Agency will continue to mo nitor the incident informat ion and if a c o ncern is triggered , additional anal ysis will be included in the risk assessment.

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### A 

## d. I M
. IDS M . S ppe n t x am 

### a1or 

### t I .d even ry net e nt 

### D escnp110n or 

### I 

### I 1propy1 h socmc omeronate. Human Incident 

# I Chem ical: Dipropyl isocinchomeronate 

# I PC Codes : 116001 , 116002 , 116004

Incident Package Incident Reg Report Date Location Number Product Name Incident Description A 50 ye ar old male has been u sing product on his bed for about three weeks and i s now feeling sick. About three days ago , he began having some shakiness , nausea , bron c hiti s and lhe bottom half of his body is 020736- 000270

- ADAMS FLEA numb. He does not have any skin irritation. H e was in a very bad car 00004 1 / 14/2 009 T AMPA , FL 00343 AND TICK MI ST accident a few years ago and is onprescription morphine for the pain
. A 54 year o ld female caller got le ss than I tsp. o f product on her hand while tran s f errin g a refill bottle of product into a sp ray bottle. She rin sed her hand off with a hose and sprayed three horses with the product. While preparing t o take a s ho wer, she felt like s h e had "thousands of bugs under her ski n" and starte d to swell rapidl y. S h e sc rubbed hands and feet with soap. She ca ll ed 911 and told them s he was hav ing an allergic reaction
. While waiting for the ambulance she p assed out. When FLYSECT she woke she wa s vomiting and continued to vomit in the amb ulance
. SUPER-7 She was give n an Ep i-Pen in the ambu lance. She also experienced 021149- 000270- REPELLENT hyp oten sion. She was given IV ste roid s. She was instructed to take 0000 1 7 / 16 / 2009 VA 00300 S PRAY Zantac twice daily and Benadryl three times per day
. A 42 year old male laid o n a couch that had been s prayed with product before it was dry
. He wa s admitted to the ho s pita l with s udden memory loss, shakin g, and arm s and legs drawn up . He was on breathing tube du e to seizure-like sympto m s . He recognized fami ly but didn't know addres s for two days. He was rambling and incoherent. He h ad been on antidepressants and F enta n yl prior to hospitalization. All testing, toxicology , MRl's came back normal. Med s were reduced. H e gradually improved and was re leased from the hospital, afte r 4 days. 

### His memo ry was b ack to normal, but it was hard for him to control his hand and 021215

- 000270- ADAMS FLEA& write. H e came home and rested on couch per in structions. He still talks 0000 1 7/27/200 9 IL 00343 TICK MI ST incoherently, experiences has double vision an d headaches. An adult f e m a le used th e product, along w ith another flea & tick spray, in tb e hou se. T hree days later, she feel s "out of it" and ex perienced headache , chest pain , shortness of bre ath , and nause a. S he works at a 021312- 000270- ADAMS FLEA clinic where th ey took her BP and said it low a nd she was not a ll owed t o 00001 9/ 9/2009 

### wv 00343 AND T IC K MI ST drive home
. S he feels like s he can ta ste the product
. 

### Page 6 of 10Human Incident 

# I C h emical : Dipropyl isocinchomeronate 

# I PC Codes: 116001, 116002, 116004

inc ident Package Incident Reg Report D ate Location Number Product Name Jnc id ent Desc rip tion Caller applied product to dog and a llow ed it to dry
. An hour late r, her ADAMS FLEA child (2 year old femal e) played with dog
. About 4 hours later, the caller 021429- BONNE TERRE, 03742 5

- AND TICK MIST noted welts on the ch ild 's arms, legs and flanks
. The child was given a 00004 10 /26/ 2009 MO 00012 320Z bath; we lts reso lved but s kin still ha s redness. A 34 year old ma le used the product 48 hou rs ago spraying the product onto his hands and rubbing hi s hands on his fac e (per label). The product 001021- COLEMAN was also applied to his arms an d legs. The caller states yesterday evening 021934- 01600- INSEC T he developed rai se d fluid filled blisters on his face and neck. His arms 00002 4/5/2010 ASH EVI LL E, NC 079533 REPELLENT am/legs app ear normal. FLYSECT 

### An adult fe mal e had water- diluted product on her bare hands, wiping SUPER-C down the cows' faces two days ago. She was in today for a recheck om a 022013- BROOKSVILLE , 000270- R EPE LLENT chronic viral illn ess ( fo r which she's taking ABX) and the HCP found 00001 5/Jl/2010 FL 00301 CONCENTRATE that she had e l evated liver enzymes. No irritation or paraesthesia Caller states that th e product has been used frequently on five
. dogs. She holds the dogs while her husband sprays them
. She has had skin contact with product two times. Since s he started using the product she experienced chest pain and d iffic ulty bre athing. Th e sy mpto ms have A D AMS FLEA& been intermittent and she thinks they sta rted the same day she u se d the 022013- 000270- TIC K MIST 16 product. She was seen in ER since symptoms started
. She ha s restarted 00002 5/14/2010 TX 00343 

# oz medication for hi gh bl oo d pressure (Norvasc 5 mg), PREVENT! An adult fema l e noticed th at the product l eaked out of the can and mixed MOSQUITO with several soaps and c leaning products under her sink. While cleani ng 001021- REPELLENT the spill she suspects the mixture may have contacted her hands. 0222 33

- BIRMINGHAM , 01600- CONTAINS Approximately 3 days late r she d evel op ed slurred speech, confusion and 0 0004 7/5/2010 AL 059 1 44 DEET25% it fe l t like he r 'heart was racing.' A 6 year old male child broke out in red raised bumps that cover his arms and legs. The child's mother sprayed her home with two products 022306- BLOOMINGTO N , 000270

- ADAMS FLEA and the child broke out a few hours later. Unsure ifthe chi ld was in the 00009 811112010 IL 00343 AND TICK MIST home during the application
. The red bumps are not itchy. A parent sprayed th e product on his 2 year old son. Four hours late r, his son deve loped a temp of 10 2 and has a red ras h on his neck and arms. 011715- CRCDOUBLE They end ed up taking child to ER. The symptom s w ere n ot from the 022306- 00085- INSECT product but mo st likely from a virus. He also developed diarrhea. He 0001 3 8/ 19/2 010 TX 055809 REPELLENT was put on an antibiotic. 

### Page 7 of 1 0Hu m an lncident 

# I Chemical: Di propy l i s ocinchomero nat e 

# I PC Codes: 116001 , 116002, 116004

Incident 

### Package lncident 

### Reg Repo1·t Date Location Number Product Name fncident Description An adult female used product on her dogs about ten hours ago. She ADAMS FLEA& rubbed it in with her hands but washed them with soap and water after. 

### 022308- 000270- TICK M I ST 

### 1 6 FL She has developed symptoms of nausea, chills , headache and anorexia 

### 00004 8/22/ 2010 OK 

### 00343 

# oz and they are getting worse . Caller used product and later on that day her grandson 

### (4 years old) was playing on the carpet and broke out in hives and a rash all over his body. ADAMS FLEA & They took the child to the doctor and were given some Benadryl and HC 

### 022308- 0 37 425

- TICK MI ST 

### 1 6 FL c re am to use . Symptoms are sl o wly getting better and the carpet w as 

### 0 0005 8/19/2 0 10 

### IL 0 00 12 

# oz sh ampo oed yesterday. A 

### 62 year old male experience d puffy eyes and nausea. He r ep orts that w hen he was trying to spray hi s dog yeste r day , it r esisted and some of the spray got on his hands and on his face. He washed with soap and water. He not flush his eyes as he did not get any of the product in them
. ADAMS FLEA He experienced musc l e tightness in his neck and shoulders after the 

### 022308- 000270- AND TICK MIST exposure occu rred
. H e took an ibuprofen after and slept for 

### 45 minutes , 

### 00006 8/24/ 2010 MI 

### 00343 32 FLOZ but woke up and did oot feel better. A 

### 24 year old female handled the p roduct on and offfo r years witho u t a prob lem. She applied the product daily to the dog u nti l she b ad two seizur es at work
. S he wen t t o E R , whe re s he had fo ur more seizures . T hey ga v e he r a val ium presc ri ption and she saw a ne urologist the next day, who gave her Tegreto l. T he neuro log ist sai d t he descr iptio n o f th e seizures made him sure they were p artia l seizures. Patient had a nosebleed and three more seizures. T he doctor changed he r prescri ption FLYS-OFF FLY to Kep ra. She had been applying the pro duct quite heavily. The dog 

### 022308- 000270- REPELLENT started havi ng seizures too. Patient is under the care of a physician and 

### 00007 8/6/2010 ST
. J OS EP H , MO 

### 00103 OINTMEN T 

### 5 OZ diagnosed with partial seizure disorder. An adult fema le sprayed product on her dogs. That night she broke ou t i n itchy hives
. She says she start ed to take Benadryl but her symptoms ha ve gotten worse. She has us e d this prod uct before with no reac t io n . Three d ays later, s he was co ve red in h ives. Her li ps , tongue and mouth ADAMS FLEA & started to fee l nu mb. She went to t he E R and was treated w ith s t e r

o i

ds 

### 022308

- 000270- TI CK MIST 

### 16 FL and some ot her medications. Symptoms are improving now : No specific 

### 00008 8/27/20 10 M I 

### 00343 

# oz cause found for symptoms b ut she re lates it to product use. 

### 022385- 91!4/2010 FORT WORT H , 

### 000270- ADAMS FLEA & Caller's husband used product in the house last night and while he was


### P age 8 of 1 0Human Incident 

# I Chemical: Dipropyl isocinch omeronate 

# IPC Codes: 

### 116001,116002, 116004

Incide nt Package Incid e nt Reg Report Date Location Number Product Name Incident Description 00001 TX 00343 TICK MIST 16 FL spraying the odor became very strong and she developed a sore throat 

# oz and hard coughing and asked him to stop spraying. In the morning she vomited, felt cold , had increased urination and abdominal pain below her ribs. She has severe allergies, especially to some antibiotics, and she is asthmatic. She can still smell the product 

### in the home and she is extremely sensitive to odors. She went to a HCP who gave her an antiemetic and other meds. She mentioned she developed a high fever followed by being ice cold after her exposure to the product. For the 2nd and 3rd day she mainly had nausea and a little diarrhea. A 59 year old male used the product and within 24 hours he developed 001021- BENGAL lower back pain. He was evaluated by the MD and was told he had a 022492

- WEST MONROE, 01600- MOSQUITO pinched sciatic nerve. He was prescribed an anti-inflammatory 00003 9/14/2010 LA 068543 REPELLENT medication and an antibiotic and given an injection. A 33 year old female used both products on her dogs in the morning and late afternoon she developed an itchy rash on both arms fro m her wrist to elbow. Both arms were exposed to the product. She washed her arms off
. 022677- 000270- ADAMS F LEA& She app li ed HC cream and took Benadryl and it temporarily helped he r 00004 1/4/2011 GA 00343 TICK M I ST symptoms. Product was sprayed on caller's 7 year old daughter's arms and legs. She 001021- PREVENT! developed a small rash that spread to her arms and legs. One leg feels 023098- 01600- MOSQUITO warm and is swollen. She went to the doctor and was prescribed l% 00005 6/l8/2011 CUMMING,GA 059144 REPELLENT hydrocortisone. She was not improving at the time of the call. An adult female states that about haifa bottle was used on floor for a black ant invas ion . Doors and windows were open for ventilation when ADAMS FLEA& used. Two hours later, she experienced voice hoarseness and sore throat. 023241

- 000270- TICK MIST 16 A 24-year-old male in the home is spitting up bright red
. He was 00003 7/4/2011 NM 00343 

# oz sleeping when the product was used. A 53 year o ld male used the product several times over the last week or 001021- ZEPSTA-A

- WAY so, and he developed a red rash on his legs and forearms. His physician 023329- 01600- INSECT recommended that he take Prednisone to treat his symptoms, but he 00004 817/2011 BUFFALO, NY 001270 REPELLENT reports that his symptoms have not dissipated. ADAMS PLUS A 29 year old female dipped her dog with diluted product. Unknown if 023534

- 000270- PYRETHRIN DIP she was wearing gloves or no t. The next day, she developed breathing 00002 10/1/2011 NICEVILLE, FL 00349 40Z problems
. Three days later, she developed symptoms of pneumonia. She 

## Page 9 of 10Human Incid e nt 

# I Chemica l: Dipropyl i soci ochomeronat e 

# I PC Codes: 116001 , JJ6002 , 116004

Incident Package Incident Reg Report Date Location Number Product Name Incident Description was admitted t o the ho s pital from the ER as the pneumonia became worse. She was put on antibiotics and IV fluid s and unknown other meds. She developed hypercalcemia and the leve l s were dropping. Dog became sick as well an d has been to the vet for treatment. NAPCC rep told caller that dog's symptoms were not typical for the product
. Daughter is also being treated for thyroid cancer.



### Page 10 of 10