Document ID: EPA-HQ-OPP-2009-0121-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-03-25T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 		     WASHINGTON, D.C. 20460

 ADVANCE \d61 			ICE OF PREVENTION,

OFFICE OF PESTICIDES AND TOXIC SUBSTANCES        

MEMORANDUM

DATE:		                                                                 
        February 13, 2009

SUBJECT:	Summary of Ecotoxicity Data for Capsaicin Registration Review 

				EPA Reg. #: 

 				Reg. review Case #:  4018

				Chemical Class: Biochemical

PC Code : 070701

CAS Number:  404-86-4

FROM:		Miachel Rexrode, Ph.D, Senior Biologist        /S/

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P)

TO:			Chris Pfeifer, Regulatory Action Leader     /S/

Biochemical Pesticides Branch

Biopesticides & Pollution Prevention Division (7511P) 

ACTION REQUESTED

The following is a preliminary ecotoxicity assessment for capsaicin in
support of the Registration Review Work Plan.

RECOMMENDATIONS AND CONCLUSIONS

Executive Summary

Based on the available information for capsaicin, the Agency does not
foresee the need for additional ecotoxicity data for a new risk
assessment.  All Tier I ecotoxicity data requirements per 40 CFR
158.2060 have been waived. The non-toxic mode of action of this
compound, and biodegradability (low to no persistence) should minimize
the risks to all non-target organisms, including threatened and
endangered species. The Agency has reviewed available data (mammalian
toxicology) and found that capsaicin is practically nontoxic to
mammalian species as noted from acute inhalation, dermal, and dietary
routes of exposure. This data also suggests that capsaicin should be
practically nontoxic to all terrestrial wildlife. Since it is difficult
to assess risk of capsaicin exposure to aquatic organisms, the Agency is
requiring restrictive product label statements to minimize potential
exposure and reduce risk. However, capsaicin has a non toxic mode of
action, low use rate, and is not persistent in the aquatic environment.
This exposure scenario suggest low risk to aquatic organisms.

I. Background

Capsaicin (8-methyl-n-vanillyl-6-non) and related capsaicinoids are the
ingredients that produce the “hotness" in certain species of peppers
in the Genus Capsicum. The U.S. Department of Agriculture first
registered a product containing these actives in 1962, as a dog-attack
repellent (Reregistration Eligibility Document for Capsaicin, Case 4018,
U.S. Environmental Protection Agency, June 1992, Page 3). Currently, the
capsaicin registration has been extended as an animal repellent against
birds, voles, deer, rabbits, and tree squirrels, and for use as an
insect toxicant and repellent. Capsaicin products are also used indoors
in crack and crevice, on carpets and upholstered furniture, and outdoors
on fruit and vegetable crops, grains, ornamental plants and shrubs,
flowers, lawns, gardens and garbage bags. Because capsaicin is a
naturally-occurring substance which exhibits a non-toxic mode of action
in humans, in 1991, EPA reclassified this compound as a biochemical
pesticide.

    

Red peppers have long been used as a food without any known adverse
health effects to man. In the absence of known toxicological concerns
from the ingestion of capsaicin and related capsaicinoids, the Agency
does not believe a tolerance for capsaicin is needed to protect the
public health. Therefore, EPA has exempted capsaicin from the
requirement of a tolerance for residues in or on fruits, vegetables, and
grains (EPA, 1992).

        

II. Toxicity Profile

 NON-TARGET ORGANISMS

The basic data requirements for a biochemical pesticide consist of acute
ecological effects (Tier I) studies. Environmental fate and additional
ecological toxicity studies are required only if adverse effects are
observed in these acute studies. Regarding capsaicin, the EPA has waived
Tier I studies (Table 1.0) because of the following rationale that was
presented in the RED (EPA, 1992):

1) Capsaicin is a strong, fast-acting irritant when consumed or exposed
to the skin. Since, this compound is used to repel birds and mammals;
the Agency assumes that earlier studies are correct and that terrestrial
organisms avoid excessive and prolonged exposure to capsaicin, thus
minimizing risk to these organisms. 

2) Since it is difficult to assess risk of capsaicin exposure to aquatic
organisms, the Agency is requiring restrictive product label statements
to minimize potential exposure and reduce risk to aquatic ecosystems.

Table 1.0 Waiver Request for Ecotoxicity  Studies on Capsaicin

Study Type/OPPTS Guideline	

LD50/LC50/Results	

Classification	MRID

Avian Acute Oral/OPPTS 850.2100	Waiver	

Acceptable	47192005

Avian Dietary/OPPTS 850.2200 	

Waiver	

Acceptable	47192005

Freshwater Fish LC50/OPPTS 850.1075 	

Waiver	Acceptable	47192005

Freshwater Invertebrate/OPPTS 850.1010 	

Waiver	Acceptable	47192005

Non-target Plants/OPPTS 850.4000 	Waiver 	Acceptable	47192005

Non-target Insects 	

Waiver	Acceptable	47192005

Mammalian Tier I Toxicity (MRIDs  47192002 thru 47192011)

The summary (Table 2.0) of the most sensitive toxicity values (acute)
for mammals shows that capsaicin is a Toxicity Category IV compound. The
acute oral and acute dermal toxicity suggest that this compound is
practically non-toxic to mammals with LD50 > 5000 mg/kg. The low
exposure expected from capsaicin should not result in acute inhalation
toxicity or primary eye irritation. The results of these studies suggest
that capsaicin should not cause any acute adverse effects to mammalian
or terrestrial wildlife.

Table 2.0.  Mammalian Toxicological Data for Capsaicin

Data Requirement	LD50	Toxicity Category	MRIDs

Acute Oral Toxicity

OPPTS 870.1100	>5000 mg/kg	IV	47192008

Acute Dermal Toxicity

OPPTS 870.1200	>5000 mg/kg	IV	47192003

Acute Inhalation Toxicity

OPPTS 870.1300	Low exposure based on anticipated low rate of product
release.	IV	47192004

Primary Eye Irritation

OPPTS 870.2400	No corneal opacity, iritis, or positive conjunctival
irritation; max average score 4.0 at 1 hour after instillation.	IV
47192009

Primary Dermal Irritation

OPPTS 870.2500	Primary irritation index was 0.2 – slightly irritating
IV	47192010

Dermal Sensitization

OPPTS 870.2600	Not a dermal sensitizer	-	47192004

Classification:  Acceptable; no additional data are required.  

Endangered Species

The unique characteristics of capsaicin, its non-toxic mode of action,
low use volumes, and biodegradability (low to no persistence) should
minimize the risks to threatened and endangered species. The Agency has
calculated the potential risk to terrestrial species by relying on
Individual Effects Model Version 1.1 that predicts the chance of
individual effect at about 1 in 294,000. Based on the mammalian toxicity
data that has been submitted on the active ingredients, there should not
be toxic risk to endangered/ threatened species from exposure to the end
use product. Capsaicin should present a No Adverse Affects (NAA) to
terrestrial threatened or endangered species, if used in accordance with
approved labeling.

Table 3.0.  Individual Effects Chance Model Version 1.1 for Predicting
the Chance of Individual Effects of Capsaicin to Terrestrial Endangered
Species

IEC V1.1 - Individual Effect Chance Model Version 1.1	 

Predictor of chance of individual effect using probit dose-response
curve slope and median lethal estimate 	 

Enter LC50 or LD50	5000	 	 

Enter desired threshold 	0.1	 	 

Enter slope of dose-response	4.5	Is this a default slope estimate? Yes
or No	 

z score result	-4.5	 z is the standard normal deviate	 

Probability associated with z	3.40E-06	Uses Excel NORMDIST function to
estimate P with lower reporting limit of 1.0 E-16

Chance of individual effect,                  ~1 in .  .  .	2.94E+05
Calculated as 1/P 	 

Since it is difficult to assess risk of capsaicin exposure to aquatic
organisms, the Agency is requiring restrictive product label statements
to minimize potential exposure and reduce risk to aquatic ecosystems.
However, capsaicin’s non-toxic mode of action, low use volumes, and
biodegradability (low to no persistence) presents little exposure risk
to endangered aquatic species. Capsaicin should present a No Adverse
Affects (NAA) to aquatic threatened or endangered species, if used in
accordance with approved labeling.

Ecological Effects Summary

No risk assessment was performed for capsaicin. However, the Agency has
reviewed the available toxicity data and found that this compound is
practically nontoxic to terrestrial non-target species as noted from
acute inhalation, dermal, and dietary routes of exposure 

should not cause adverse effects relative to potential exposure to
nontarget wildlife, aquatic species, or endangered/threatened species.

III. References

1. Registration Eligibility Decision (RED) Capsaicin, Case 4018;
U.S.Environmental Protection Agency, Office of Prevention, Pesticides,
and Toxic Substances, Office of Pesticide Programs, U.S. Government
Printing Office: Washington, D.C., 1992.