repelente ir 3535

IR3535®: Several Applications

Denis Martins João

Marketing Development

October, 2011

IR3535® shield yourself, March 2011 2

Content

Section 1: Insect Repellents

Section 2: Repellent Products

Section 3: Repellent Market

Section 4: Marketing Information IR3535®

Section 5: Insect Repellent Regulations


Section 1: Insect Repellents

Definition

Mode of Action

Competitive Repellent Actives

Competitive Repellent Actives and Uses


Insect Repellents

Definition:

“Substance or formulation that causes insects to make oriented movements

away from its source.”

IR3535® is:

a personal repellent.

Intended use: human and animal use on skin, hair or clothes

a topical repellent.

Application: to chosen parts of the skin and clothes.

a synthetic repellent.

– Synthetic repellents are developed for long lasting protection

in comparison to natural repellents

– However, IR3535® is close to nature (similar structure like ß-alanin)


Competitive Repellent Actives

First repellents were derived from nature. This repellents show high evaporation. Therefore the long time protection on skin was not possible. Examples are:

Citronella

Lemon Eucalyptus derived actives (PMD)

Geraniol

Modern synthetic repellents are optimized for long lasting protection on skin. Examples are:

DEET

IR3535®

Icaridin


Competitive Repellent Actives and Uses

Protection

against:

Mosquitoes

(human use)

Protection

against:

Ticks

(human use)

Protection

against:

Flies

(human use)

Protection

against:

Lice

(human use)

Animal prod.

IR3535®

x x x x x

DEET x x x x

Icaridin x x x x

Citronella x x x x x

Eucalyptus

(PMD) x x x x x

Geraniol x x x x


Section 2: Repellent Products

Application Forms on the Market

Product Examples with IR3535®

Mosquitoes, ticks, flies protection

Lice prevention

Animal products

Other Repellent Uses


Application Forms on the Market

Intended use Target Organism Formulation

Human use on skin Mosquitoes, flies, ticks,

wasps, bees

Aerosol, pump sprays,

gel, cream, lotion,

wipe, roll-on, mousse

Human use on hair lice Pump spray

Animal use Flies, ticks, mosquitoes Pump spray, gels, wipe

Innovations are possible. In any case leave-on products are

needed. The repellent have to be available on skin or hair to be

effective. Therefore, shampoos and shower gels are not

suitable for the application of repellents.


Product Examples with IR3535® Mosquitoes, ticks and flies protection

France

Asia and

South America

Scandinavia USA in EU and Asia


Product Examples with IR3535® Lice prevention

Europe Spain Mexico France Belgium


Product Examples with IR3535® Animal products

Intended use:

horse, against

skin irritation

UK UK

Intended use:

cat and dog,

flea infestation

Germany

Intended use:

horse,

insect repellent

Germany Germany

Intended use:

horse,

insect repellent

Intended use:

human&dog,

tick protection


Section 3: Repellent Market

Example USA

Segments

Claims

Example Europe

Segments

IR3535® Children Product Market

IR3535® Animal Product Market


Example US Insect Repellent Market Segments (Target Groups)

Family Nature & Sport

„Active“ „Expedition“

„Deep

Woods“ „Family“


Example US Insect Repellent Market Segments (special products)

Soft Formulations Max-Products

„Xtreme“ „Maxi“

„soft“, „gentle“ claim example: maximum strength –

up to 10 hours protection


Claims

Efficacy Claims:

„long lasting protection“

„repels mosquitoes that may carry West Nile Virus“

„maximum strength – up to 10 hours protection“ (high concentration products)

Target Organism, for example:

„protection from ticks, mosquitoes and biting flies“

Formulation Claims:

„odorless“

„non-greasy“ / „not oily“

„resists perspiration“

„unscented“

Secondary Cosmetic Claims, for example:

„with Aloe Vera“


European Insect Repellent Market Segments (Target Groups)

Every Day „european use” Holiday „tropical use“

„Tropic“

35% IR3535®

„Jungle

Formula“ „European

Lotion“ „Europe“

claim example: extra strong formula –

up to 8 hours protection


Children adults

adults and

infents

infents

not

specified

22%

12%

28%

37%

European Insect Repellent Market IR3535® Children Product Market

22% of products are

specific for infants

59% of products are

claimed for infants


European Insect Repellent Market IR3535® Animal Products Market

horse (dog)

market

cat and dog

market

fleas

horse fly,

ticks, flies,

mosquitoes

The horse market dominates Animal


Section 4: Marketing Information IR3535®

PROS of IR3535®

Broad Spectrum of Efficacy

Long Lasting Protection

Close to Nature

Excellent Toxicological Profile

Gentle to the Environment

IR3535® in Children Products


PROS of IR3535®

Marketed since more than 30 years in Europe

Broad spectrum of efficacy (1)

US-CDA recommendation for “long lasting protection” (2)

“Close to nature”: structural similarity with natural occurring ß-alanine (3)

Excellent toxicological profile (classification as Bio-Pesticide in USA) (4)

No danger symbols required for product labeling of IR3535®

Gentle to the environment (biodegradable) (5)

Excellent cosmetic properties: odourless liquid, highly stable

excellent skin feeling

For all this reasons preferred active for especially

children products (6)


Broad Spectrum of Efficacy (1)

Mosquitoes

Ticks

Lice

Stable flies

Black flies

Sand flies

Deer flies

Biting midges

House flies

Wasps

Bees

Claims with

IR3535®:

Efficacy IR3535®

Repelling effect of is proven for:

Mosquitoes (Aedes spec., Culex spec.

and Anopheles spec.)

Ticks (Ixodes scapularis and Ixodes ricinus)

Lice (Pediculus humanus corporis and capitis)

Stable flies (Stomoxys calcitrans)

Black flies (Simuliidae)

Deer flies (Tabanidae)

House flies (Musca domestica)

Wasps (Pollistes galliens)

Bees (Apis melifera)

22


Broad Spectrum of Efficacy (1) Year Author / Institute Type Target organism

1975 Kuhlow, F.

Bernhard Nocht-Institut, Hamburg

Field test Mosquito An. funestus/gambiae

Black Fly Simulium

1981 Liebisch A.

Tierärztlichen Hochschule, Hannover

Lab test Mosquito Aedes aegypti

1982 Buescher M.D. et al. Lab test Sand fly Lutzomyia longipalpis

1989/

1990

Research Laboratory of Dainihon Ichugiku

Co., Tokyo, Japan

Field test Mosquito Aedes albopictus

1992 Coosemans N.

Institute of Tropical Medicine, Belgium

Lab test Mosquito Aedes aegypti

1993 Combescot C.

Faculty of Medicine,Tours, France

in-vitro

test

Louse Pediculus humanus

1993 Combescot C.


in-vivo

test


1995 Burgess I.

Medical Entomology Centre, Cambridge, UK

in-vitro

Test

Fly Musca domestica

1995 Roubier C.

BIO-TOX S.A.R.L. Vallauris, France

in-vitro

Field test

Wasp Polistes galliens,

Bee Apis melifera

1996 Buczek A.

Silesian Medical Academy, Katowice, Poland

in-vivo

lab test

Tick Ixodes ricinus



1996 Benzon G.L.

Benzon Research, Carlisle, PA, USA

in-vitro

lab test

Tick (Nymphs) Ixodes scapularis

1996 Broce A.B.

Department of Entomology, KS, USA

in-vitro

lab test

Stable fly Stomoxys calcitrans

Fly Musca autumnalis

Cat flea Ctenocephalides felis

1996 Cilek J.E.

Mulrennan Research Laboratory A&M, FL, USA

Lab test

Ticks Ixodes scapularis


1996 Hunter F.

Department of Biologicsal Sciences, St. Catharines

in-vitro

lab test

Black fly Simulium venustum

Deer fly Chrysops ssp


1998 Shashina N.I.

Russion Acedemy of Medical Sciences, Moscow

Lab test Mosquito Aedes aegypti, Culex

pipiens

1998 Yap H.H. Vector Control Research Unit, Malaysia Lab test Mosquito Aedes albopictus,

Anopheles maculatus

1998 Yap H.H. Vector Control Research Unit, Malaysia Field test Mosquito Aedes albopictus,

Culex quinquefasciatus

2000 Mulitinovic et al.

EKOSAN Co. Faculty of Pharmacy, Yugoslavia

In-vivo lab

test

Mosquito Aedes aegypti

2000 Usavadee et al.

National Institute of Health, Nonthaburi, Thailand

Lab test

Field test

Mosquito Aedes aegypti,

Culex quinquefasciatus, Culex

Tritaeniorhynchus, Anopheles dirus



2002 Peter B.A. et al

Department of Health Sciences, Sydney, Australia

Field test Mosquito Verrallinia funerus,

Ochlerotatus vigilix, Aedes aegypt

Bitting midge Culicoides ornatus

2004 Cilek J.E.

Mulrennan Research Laboratory A&M, FL, USA

Lab test Mosquito Aedes aegypti, Culex

quinquefasciatos

2005 Naucke T.J. et al

Institute for Medical Parasitology, Bonn, Germany

Lab test Sand flies Phlebotomus mascittii,

Phlebotomus duboscqi

2006 Scott Carroll

Carroll-Loye Biological Reserch, Davis, CA, USA

Field test Mosquito Anopheles freeborni,

Aedes melanimon, Aedes

vexans, Aedes nigromaculus,

Culex tarsalis, Culex

erythrothorax, Culiseta incidens

2006 Scott Carroll

Carroll-Loye Biological Reserch, Davis, CA, USA

Lab test Ticks Ixodes scapularis

2007 Hill N., (Kröpke R. et al.)

London School of Hygiene and Tropical Medicine,

London, UK

Field test Mosquito Anopheles darlingi,

Anopheles albitarsus, Aedes aegypti,

Culex pedroi

2009 Combescot Catherine


in-vitro

test


Presentation title in footer | 00 Month 0000 26

IR3535®: Cage Test with Sand Fly

0,00 2,00 4,00 6,00 8,00 10,00 12,00

P. duboscqi

P. mascittii

Protection time on hours (h)

Deet 10% IR3535® 10%

Naucke (2006) Laboratory testing of the insect repellents IR3535® and Deet against Phlebotomus

mascittii and P. duboscqi (Diptera: Psychodidae)

Study Type Cage Test

(Germany)

Conditions 2 Volunteers (male and

female), each 5 repetitions,

1g test substance,

EPA Guideline OPPTS

810.3700

Species Phlebotomus mascittii

Phlebotomus duboscqi,

(sand fly)

Tested material IR3535® / Deet

10 % solution in ethanol

Comparable and better

protection with IR3535®

in comparison

with Deet

Presentation title in footer | 00 Month 0000 27

Product examples from Europe 1

Product name: Anti-Phebotome® - spray and collar

Company: Tafarm (veterenay products, Greece)

Active Substance: DEET (spray)

http://www.tafarm.gr/main.html

Efficacy IR3535®: Mosquito

Aedes albopictus:

CDC Public Health Image Library

The efficacy of IR3535®

is approved by cage and field

studies with e.g.:

Aedes albopictus and aegypti

Anopheles dirus and darlingi

Culex quinquefaciatus and

tritaeniorhyncus

28


Long Lasting Protection (2)

In May 2008, the US-CDC

recommended the use of

IR3535®:

“products containing these active ingredients

typically provide reasonably long-lasting

protection”.

CDC, Centers for Disease Control

www.cdc.gov/ncidod/dvbid/westnile/repellentupdates.htm.


Close to Nature (3)

Chemically, the structure of IR3535® can be regarded as

derivative of the natural occurring amino acid “beta-alanine”.

O

N

O

OC 2 H 5

N H 2 O H

O

ß-alanine


Excellent Toxicological Profile (4)

IR3535® “is

practically non-toxic

to mammals including

infants

and children…”

EPA registration as Biopesticide

US-EPA classification:

Please compare with Section 6, Regulations in USA


Gentle to the Environment (5)

IR3535® - Closed bottle test (OECD 301D):

Biodegradation of 11% after 28 days Sewage treatment simulation assay (OECD 303A):

Biodegradation at 99% and showed

complete mineralization

Biodegradation


IR3535® in Children Products (6)

Documents about safety of IR3535® in children products:

MERCK KGaA, INSTITUTE OF TOXICOLOGY Calculation of MOS (Margin of Safety): ”…20% formulation does not represent a risk to the general population including children” “However, as a precautionary measure we recommend not to use IR3535® in children <12 months, as several physiological functions (excretion metabolism) are not fully developed in newborn and maturate within the first twelve months”. please contact: Dr. AM Bohlmann, [email protected]

RUSSIAN MINISTRY FOR HEALTH PROTECTION CONCLUSION on the results of the investigation of repellent (active substance) IR3535”: “…IR3535 can be used as a component of various preparation forms on human skin directly, and prepared according to specific formulations – on the skin of children of various age groups (from one year of age and older)” please contact: Dr. AM Bohlmann, [email protected]

EPA web-page: see section E - Human Health Effects, Acute and Chronic Dietary Risks for Sensitive Subpopulations, Particularly Infants and Children: IR3535® “is practically non-toxic to mammals including infants and children…” http://www.epa.gov/pesticides/biopesticides/ingredients/tech_docs/tech_113509.htm

Remark: before age recommendations will be claimed on a product label, national

recommendations should be checked (example France: general recommendation > 30 month).


Section 5: Insect Repellent Regulations

Global Insect Repellent Regulations

Regulations in Asia/Pacific

Regulation in European Union (EU)

Regulations in South America

Regulations in USA


Global Overview

Country/Region Registration Comments

Asia/Pacific Different types of registration Registered and marketed in some countries

Australia NRA registration Approved 2000

European Union Biocidal Products Directive Dossier submitted, review ongoing

South America Different types of registration Registered and marketed in most countries

USA EPA registration Approved 1999

WHO WHOPES evaluation and recommendation Approved 2001


European Union

Insect Repellents will be regulated under Biocidal Product Directive (BPD) in the EU

Existing active substances are currently under review (like IR3535®).

Active substances which pass the review will be listed in a “positive list” in Annex I of the BPD (time line for IR3535®: listing in Annex I in about end of 2013 or beginning of 2014).

The date of the listing of an active substance in Annex I is the deadline for submission of dossiers for existing products.

Overall Goals of BPD:

Harmonization of biocides legislations in the EU

Authorization / registration of biocidal products before marketing

Until listing of the active substance in Annex I national legislations are still valid in any EU country (transitional periode)


European Union (transitional periode)

country legislation marketed countery legislation marketed

Austria Biocide notification yes Italy Medical Device yes

Belgium Biocide registration yes Latvia Agency for Env. n.i.a.

Bulgaria Biocide notification n.i.a. Lithuania Biocide registration yes

Cyprus Registration yes Luxembourg Depends on use n.i.a.

Czech Rep. Registration yes Poland Biocide registration yes

Denmark Biocide registration no Portugal Registration yes

Estonia Biocide registration n.i.a. Romania Biocide registration n.i.a.

Finland Biocide registration yes Slovac Rep. Registration yes

France Biocide declaration yes Slovenia Biocide notification yes

Germany Biocide notification yes Spain Registration yes

Greece Registration yes Sweden Biocide registration yes

Hungary Depends on use yes Netherlands Biocide registration no

Iceland n.i.a. n.i.a. UK Depends on use yes

Ireland Biocide notification yes

n.i.a. = no information available


South America

Country Type of registration Registration for registered marketed

Argentina Cosmetic (ANMAT) FP (human use) not needed yes

Brazil Cosmetic (ANVISA) FP (class 2) not needed yes

Chile yes

Columbia IA, FP yes yes

Ecuador yes

Mexico Cosmetic (COFEPRIS) IA, FP yes yes

Peru Cosmetic yes

Venezuela IA?, FP yes

AI = active ingredient

FP = finished product IR3535® status

Harmonization process in South America: Cosmetic regulations were discussed in

Mercosul (Argentina, Brazil, Paraguay and Uruguay), such as good manufacturing

practices and demands of registration of cosmetics. The harmonized text have to be

nationalized in each country.


USA

Country Type of registration Registration for registered marketed

USA Bio-Pesticide AI, FP yes yes

In 1997, EPA-OPP's Biochemical Classification Committee classified

IR3535® as a biochemical, based on facts that it is functionally

identical to naturally occurring beta alanine in that both repel insects,

the basic molecular structure is identical, the end groups are not

likely to contribute to toxicity and it acts to control the target pest via

a non-toxic mode of action (1). Therefore, the insect is not affected

by IR3535®.

(1) http://www.epa.gov/pesticides/biopesticides/ingredients/tech_docs/tech_113509.htm

AI = active ingredient

FP = finished product IR3535® status


IR3535® Ordering and Product Information

Ordering information

Item NO Name Pack size

111887 Insect Repellent IR3535® 1 kg, 25kg, 200kg

For SDS and Specification http://www.merck4cosmetics.com/

For more Detail Information and

Technological Support please contact: Dr. AM Bohlmann, [email protected]

repelente ir 3535

Documents

repellent uses ir3535

ir3535 mosquitoes

deet ir3535 icaridin

asia ir3535

alanin ir3535

tick protection ir3535

ir3535 animal products

repellent products section