UNITED STATES ENVIRONMENTAL PROTECTION AGE NCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND

POLLUTION PREVENTIO N

MEMORAND UM

Date: May 20, 2010

SUBJECT: Limonenc: Review of Human Incidents

PC Code: 079701

Decisio n No.: NA

Pet ition No.: NA

Risk Assessment Type: NA

TXR No.: NA

MRID No.: NA

DP Barcode: D374493

Registration No.: NA

Regul at ory Action: NA

Case No.: NA

CAS No.: 138-86-3

40 CFR: NA

FROM:

THROUGH:

Sarah Winfield, Biologist.J Fs;-::~N~~jJ:;. f.:::)Jo-- Shanna Recore. Industrial Hy ist

Khin 0 0, M.D., MPH, Environmental Health Scientist

Tox icology and Epidemiology Branch - =-- Health Effect Division (7509P)

Mary Manibusan, Branch

Toxicology and Epidemiology Branc t...,-c.------....

Health EfTects Division (7509P)

VeT.Apr.lOIO

TO: George Kramer, Risk Assessor

Risk Assessment Branch I

Health Effects Division (7509P)

and

Russell Wasem, CRM

Risk Management & Implementation Branch I

Pesticide Re-evaluation Division (7508P)

I. CONCLUSION

Based on the low frequency and severity of incident cases, 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 .

Page I of 5
II. ACTIO N REQUEST ED

This review is intended to fulfill our requirement to docket summaries of incident data that were

reported to the Agency, as well as to ensure human incident data, and the Agricultural Health

Study are part ofthe problem formulation phase of registration review. Reports of adverse health

effects 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 reported symptom (or the

connection between the two) is validated. Typically, causation cannot be determined based on

incident da ta. However, incident information can be an important feedback loop to the Agency -

incidents of severe out come, or a suggested pattern or trend among less severe incidents can

signal the Agency to further investigate a particular chemical or product. Observational

epidemiology studies relate the risk of disease, e.g., cancer, and exposure to an agent such as a

pesticide product in the gene ral population or specific sub-groups like pesticide applicators.

Ill. BACKGROUND

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease

Control and Prevent ionlNational Institute for Occupationa l Safety and Health (CDCINIOSH)

Sentinel Event Notification System for Occ upationa l Risk-Pesticides (SENSOR) database were

consulted for pesticide incident data on the active ingredient limonene. Additionally, the Agency

is looking to include findings from the Agricultural Health Study (AHS), beginning wi th the

problem formulation phase of registration review. The purpose of the database searches is to

identify potential patterns on the extent and seve rity of the health effects attributed to limonene

ex posure. The IDS includes reports of alle ged human health incidents from various sources,

including mandatory Federal Insecticide, Fungicide and Roden ticide Act (FIFRA) Section 6 (a)

(2) reports from registrants, other federal and state health and environmental agencies and

individual consumers. Since 1992, OPP compiles these reports in IDS. IDS contains reports

from across the U.S. and most incidents have all relevant product information recorded. Reports

submitted to the IDS represent anecdotal reports or allegations only, unless otherwise stated in

the report. The NIOS H SENSOR database covers 12 states from 1998-2006. although reporti ng

varies from state to state (the database includ es a total of 10,659 cases). Pesticide-related

incidents are collected from Department of Labor workers' compensation claims when reported

by physicians, reports from State Departments of Agriculture, from poison control centers and

from State Departments of Health based on reports by physicians suspecting pesticide exposure.

Although both occupational and non-occupational incidents are included in the database,

SENSOR focuses on occupational pesticide incidents, and is of particular value in prov iding that

inform ation. A state SENSOR contact specialist does follo w-up with workers and obtains

medical records to verify symptoms, circumstances surrounding the exposure, severity, and

outcome. Using standardized protocol and case definitions, derived from poison center

reporting, SENSOR coordinators at State Departments of Health enter the incident interview

description provided by the worker, medical report, physician and patient into the SENSOR data

system, acce ssible to participating slates and EPA. The AHS is a high quality, prospective

epidemiology study evaluating the link between pesticide use and vario us health outcomes

includ ing cancer. The AHS includes private and commercia l pesticide applicators and their

spouses. If there are AHS findings relevant to a particular pesticide going through registration

Page 2 of 5
review, the Agency will ensure they are considered in the problem fonnulation/scoping phase of

the process and, if appropriate , fully reviewed in the risk assessment phase ofthe process. The

AHS includes information on the use of 50 different pesticide active ingredients commonly used

in agriculture.

IV. RESULTS/DISCUSSION

For IDS we identifi ed 39 cases reported for limonene in the United States from 2002 to the

present. Of these cases, live were reviewed because in these cases limonene was used as a single

chemical only and there fore these cases provide more certain information about the potential

effects of limonene exposure. Three of the cases appeared to involve ex posure from using a flea

and tick shampoo containing limonene in residential settings, and the rema ining two cases

involved postapplication exposure in residential settings (after professional app lication). The

most frequently reponed symptoms were neurological (38%) follo wed by dermal (25%) ;

gastrointestinal, ocu lar and miscellaneous symptoms were reported equally (13%) . Proportions

relate to the total number ofsymptoms, not the total number of cases, i.e., an individual may

report multiple symptoms to the database. See the table below for further details.

For NIOSII SENSOR, we identifi ed 4 cases reported that involve the active ingredient limonene

Of these cases, onl y one was reviewed because, in this case , limonene was used as a single

chemical only and had a certainty classification of definite. probable, or possible. The case was

an unknown age male who had a postapplication exposure to limonene when he entered an office

that had just been treated. He experienced ocular, respiratory. neurologica l and gastrointestinal

symptoms. This cas e was ranked low seve rity.

Limonene is not included in the AHS, and therefore not considered in this report.

Based on the low frequency and severity of incident cases, there does not appear to be a concern

at this time that wou ld warrant further investigation . Although there are incidents reported that

resulted in moderate outcomes, the symptoms and settings were varied and do not indicate a

trend or pattern that would trigger follow-up analyses. The Agency will continue to monitor the

incident information and if a concern is triggered, additional analysis will be included in the risk

assessment.

Page 3 of 5
Adu lt (18-64 year old) female bathed her pel

with the product without gloves on 3 separate

occasions. She recently developed memory

deficit, confusion, pain in muscles and joints,

and difficulty expressing her thoughts in words.

Incident Descrmnon

Exposure

Type·

LA HC

Ci t· · Sta le

Human Incidents

Registrati on

Number

00475800141

Prod uct Name

ADAMS FLEA & TICK

SHAMPOO WITH DL1MONENE

tnctdcnt

Dale

OS-Jan07

Incident

Number

IDS Report

Chemical: Limonene

",,,,,.."'.."""'-'

01 8344 I 001

018666 I 01 2 25-Jun07ADAMS FLEA & TICK

SHAMPOO WITH DL1MONENE

00475800141 NC HC Adult (18-64 year old) female was exposed to

the product dermally 3 days ago. She broke out

with bumps from knees to the top of her foot.

She washed and applied Gold Bond but lesions

were still there and not resolving. Later she

used hydrocortisone ointment, and the

symptoms got better.

019670 002 29-Mar08PRESCRIPTION

TREATMENT BRAND

PROCITRA-DLTM

CONTACT

00049900497 GA HC Adu lt (18-64 year old) female reported that pest

control sprayed her home; told her that it was

alright for her to stay in the area , The next day

she started feeling lethargic, also had

headache, vomiting and diarrhea , Her dog was

also exposed to the product and developed

vomiting, dehydration, fatigue, kidney failure,

and abnormal liver function. The dog's platelets

level was low, blood stopped clotting and began

hemorrhaging under the skin. DMV gave the

dog IV fluids, antibiotics and a cortisone shot,

but the dog died .

Page 4 of 5
IDS Report

Chemical: Limunenc Human In cid ents

Incident

Number,

019849 I 002

021325 I 020

• Seven . Catc ones

H ll 11man

II-A Human Falahl'

H-B Human Major

Incident

nate

25·Jun·

08

20-Sep09

_ Product Name

PRESCRIPTION

TREATMENT BRAND

PRDCITRA-DLTM

CONTACT

ADAMS D-L1 MONENE

FLEA & TICK SHAMPOO

Regist ration

Numbcr._

00049900497

00272400759

000270

Ci ty

ANAHEIM

Stale

CA

AZ

Exposure

,T:ype*

HC

HC

Inciden t Description

A 73 year old ma le was exposed to the product

when a professional extermination company

spra yed his home with the product. He

developed headache. and painful left eye the

next day. He went to his physician for

treatment. He took Allegra D and the symptoms

lot better.

Adult (18-64 years old) male got the product on

his feet, stomach. forearms and hands when

washing the dog with the produ ct. The next day

he developed hives and welts on his stomach

and forearms. The dog was also drooling.

H-C Human Moderate

H-D Human Mirmr

H-E Human Unspecified

Pagc 5 0f 5