Pharma&Biotech
MicrobialControl
Environmental Considerations in The Selection
of Dry Film Biocides
Dilipraj T K / Lonza Inc. (Arch Chemicals Division)
Overview

Microbial control challenges for a coatings formulator


The value of biocides and the impact of the lack of protection
Challenges faced by a coatings formulator





Multi-region dry film biocide panel study

Lonza’s active agent offerings for dry film protection






Limited number of biocide active agents available
Need for long term and broad spectrum protection of the paint film
Biocide compatibility with the paint formulation
Concern about consumer perceptions opposite label warnings
The ZOE formulation of Zinc Omadine™
Formulations for other active agents
Study experimental design
Summary of study results
Introduction of Densil™ ZOD and Densil™ FAZ
Support from Lonza
2
Challenges Faced by a Coatings Formulator:
Compatibility

Challenges for a coatings formulator
Biocide compatibility with the paint formulation
Paint film protection agents must………

be chemically stable &
compatible with paints
not affect paint application
(viscosity, drying etc.)
deliver long lasting
film protection
3
Challenges Faced by a Coatings Formulator:
Broad spectrum protection

Challenges for a coatings formulator


The value of biocides and the impact of the lack of
protection
Challenges faced by a coatings formulator
 Broad spectrum protection of the paint film


Interior
 Wide variety of fungi
 Concern about indoor air quality; airborne
fungal spores
 Frequent human contact with painted
surfaces
Exterior
 Wide variety of fungi
 Defacement by algae
 Increasing diversity of substrates
4
Challenges Faced by a Coatings Formulator:
Limited biocide actives available

Challenges for a coatings formulator


Limited number of available biocide active agents
Need for both long term and broad spectrum protection of the
paint film
Fungicidal
Algaecidal
Fungicidal/Algaecidal
Octyl Isothiazolinone (OIT)
Diuron
Zinc Omadine™ (ZnOM)
Dichloro Octyl Isothiazolinone (DCOIT)
Irgarol
N-butyl Benzisothiazolin (BBIT)
Terbutryn
Iodo Propynyl Butylcarbamate (IPBC)
Chlorothalonil (CTL)
Carbendazim (BCM)
5
Challenges Faced by a Coatings Formulator:
Considering biocide solubility and spectrum




Limited number of available biocide active agents
Need for long term and broad spectrum protection of the paint film
Active agents have different water solubility and different microbial
spectrum
Why is water solubility important?
Biocide Active Agents Grouped by Water Solubility
Group A
Low Water Solubility
Group B
Medium
Water Solubility
Group C
High Water Solubility
Zinc Omadine™ (ZnOM) 0.008 gm/L
Diuron 0.035 gm/L
Octyl Isothiazolinone (OIT) 0.48 gm/L
Chlorothalonil (CTL) 0.0006 gm/L
DCOIT 0.014 gm/L
N-butyl Benzisothiazolin (BBIT) 0.7 gm/L
Carbendazim (BCM) 0.008 gm/L
Terbutryn 0.025 gm/L
Iodo Propynyl Butylcarbamate (IPBC)
0.168 gm/L
Irgarol 0.007 gm/L
6
Challenges Faced by a Coatings Formulator:
Considering biocide solubility and spectrum

Need for long term and broad spectrum protection of the paint film

Active agents have different water solubility and different microbial spectrum
 Why is water solubility important?
In the conventional model of a paint film there is a reservoir of fungicide active agent
in the paint film, and there is also some fungicide on the surface of the paint. As rain
falls on the surface of the paint film, it washes away the fungicide on the surface,
however the fungicide at the surface of the film is replenished by new fungicide
that is drawn from the reservoir in the paint film.
If the fungicide has too high a water solubility,
then the reservoir will be depleted and the coating will show defacement
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
No growth
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
No growth
O
O
O
O
O O
O
O O
No growth
O
O
O
O O
O
O O
Heavy growth
7
Challenges Faced by a Coatings Formulator:
Considering biocide solubility and spectrum

Group A
Low Water Solubility
Group B
Medium
Water Solubility
Group C
High Water Solubility
Zinc Omadine™ (ZnOM) 0.008 gm/L
Diuron 0.035 gm/L
Octyl Isothiazolinone (OIT) 0.48 gm/L
Chlorothalonil (CTL) 0.0006 gm/L
DCOIT 0.014 gm/L
N-butyl Benzisothiazolin (BBIT) 0.7 gm/L
Carbendazim (BCM) 0.008 gm/L
Terbutryn 0.025 gm/L
Iodo Propynyl Butylcarbamate (IPBC)
0.168 gm/L
Irgarol 0.007 gm/L
If the fungicide has too low a water solubility,
then not enough fungicide is pulled from the reservoir to prevent defacement
O X
X O
X
X
X
X
X
X
O X
X O
X
X
X
X
X
X
O X
X O
X
X
X
X
X
X
No growth
O X
X O
X
X
X
X
X
X
O O X
O X
X
X
X
X
X
X
O X
X
X
X
X
X
X
X
O X
X
X
X
X
X
X
X
Light growth
O
X
O O
O
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Moderate growth
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
O O
O
X
X
X
Heavy growth
X
8
Challenges Faced by a Coatings Formulator:
Considering biocide solubility and spectrum

Group A
Low Water Solubility
Group B
Medium
Water Solubility
Group C
High Water Solubility
Zinc Omadine™ (ZnOM) 0.008 gm/L
Diuron 0.035 gm/L
Octyl Isothiazolinone (OIT) 0.48 gm/L
Chlorothalonil (CTL) 0.0006 gm/L
DCOIT 0.014 gm/L
N-butyl Benzisothiazolin (BBIT) 0.7 gm/L
Carbendazim (BCM) 0.008 gm/L
Terbutryn 0.025 gm/L
Iodo Propynyl Butylcarbamate (IPBC)
0.168 gm/L
Irgarol 0.007 gm/L
A combination of a less water soluble fungicide with a
more water soluble fungicide gives more robust paint film protection.
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O O X
O X
X
X
X
X
X
X
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O
X
O
X
O
X
O
X
O O
O
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
O
X
O
X
O
X
O
X
X
O
X
O
X
O
X
O
O O
O
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
9
No growth
No growth
No growth
No growth
Challenges Faced by a Coatings Formulator:
Developing a strategy for dry film protection

Need for long term and broad spectrum protection of the paint film

Active agents have different water solubility and different microbial spectrum

Potential blend strategy

Less water soluble fungicide as a foundation

May include more water soluble co-fungicide

May include a supplemental algaecide
Troy
Troy
Troy
Thor
Thor
Troysan™ 663
Troysan™ 678
Troysan™ 662
Acticide™ PA
Acticide™ PM
9.0% BCM
3.0% IPBC
15.0% Diuron
15.0% BCM
5.0% IPBC
12.0% BCM
4.0% IPBC
4.0% Irgarol™
11.8% CTL
6.0% OIT
19.0% Diuron
14.0% CTL
19.0% Diuron
Dow
Dow
Ashland
Ashland
Lanxess
Rocima™ 63
Rocima™ 65
Fungitrol™ 2010
Fungitrol™ 2002
Preventol™
A14D
7.5% BCM
2.7% OIT
20.0% Diuron
9.0% BCM
5.0% DCOIT
3.5% Irgarol™
20.1% CTL
10.1% IPBC
48.0% CTL
10.0% BCM
3.0% OIT
22.0% Diuron
6.0% Irgarol™
Data Source; NPIRS http://npirspublic.ceris.purdue.edu/ppis/
10
Challenges Faced by a Coatings Formulator:
Consumer perceptions about label warnings

Challenges for a coatings formulator




Limited number of available biocide active agents
Concern about consumer perceptions opposite label warnings
For durable film protection, need a fungicide with low water
solubility; Carbendazim, Chlorothalonil, Zinc Omadine™
Carbendazim


Pluses
 Stable over wide pH range
 Good compatibility history with other paint ingredients
Minuses
 Very limited activity against algae or bacteria
 Gaps in anti-fungal spectrum – ex. Alternaria sp.
 CLP / GHS labeling

EU Category 2 Mutagen => GHS Category 1B
11
Challenges Faced by a Coatings Formulator:
Consumer perceptions about label warnings

Challenges for a coatings formulator



Limited number of fungicide and algaecide active agents
Concern about consumer perceptions opposite label warnings
Current situation in Europe



The European Union has now implemented the United Nations' GHS (Globally Harmonized
System of Classification and Labeling of Chemicals) into EU law as the CLP Regulation
The CLP Regulation which came into force on the 20th January 2009 requires manufacturers
to: Classify, Label and Package substances and mixtures according to CLP before placing
them onto the market
 Implementation for Substances - Dec 2010
 Implementation for Mixtures (Paint) - June 2015
In 2015, in Europe, the CLP legislation will limit the fungicide and algaecide concentrations
that can be in European paints without having warning statements on the paint cans
 EU warning statements and risk phrases for Carbendazim
 Health Hazard label
 Environmental Impact label
 GHS dosage thresholds
12
Carbendazim EU Labeling Requirements
Carbendazim
Level %
Symbol
Indication of
Danger
R and S Phrases (On Label)
<0.1
0.1 - 0.25
None
T
None
Toxic
None
R46, S53, S45 MSDS Phrase; Mutagen Cat 2
0.25 -0.5
T
Toxic
R46, R52/53, S53, S45 MSDS Phrase;
Mutagen Cat 2
0.5 - 2.5
T
Toxic
R46, R60, R61, R52/53, S53, S45
MSDS; Mutagen Cat 2, Reprotox Cat 2*
2.5 - 25
TN
Toxic Dangerous for
the environment
R46, R60, R61, R51/53, S53, S45, S60,S61
MSDS; Mutagen Cat 2, Reprotox Cat 2*
Carbendazim must be listed on the label
as a hazardous ingredient at levels >0.1%
T = Skull and crossbones
N = Dead fish and tree
* EU/DDP classification
R46 = May cause heritable genetic damage
R52 = Harmful to aquatic organisms
R53 = May cause long term adverse effects in the aquatic environment
R60 = May impair fertility
R61 = May cause harm to the unborn child
R51 = Toxic to aquatic organisms
Carbendazim potentially requires both health hazard and environmental hazard labels
13
Comparison of EU and GHS Criteria
EU
Criteria
Category 1 T R46
Category 2 T R46
Category 3 Xn R68
Substances known to
be mutagenic to man.
Substances which should be regarded
as if they are mutagenic to man.
Substances which cause concern for
man owing to possible mutagenic effects.
GHS
Criteria
Category 1
Category 2
Category 1A
Category 1B
Chemicals know to
induce heritable
mutations in germ
cells of humans.
Chemicals which should be regarded as
if they induce heritable mutations in
germ cells of humans.
Chemicals which cause concern for man
owing to the possible that they may
induce heritable mutations in germ cells
of humans.
Table 3.5.1
Cut-off values/concentration limits of ingredients of a mixture classified as germ cell mutagens that would
trigger classification of the mixture
Ingredient classified as:
Cut-off/concentration limits triggering classification of a mixture as:
Category 1 mutagen
Category 1 mutagen
Category 2 mutagen
Category 2 mutagen
> 0.1%
> 1.0%
Under GHS, Carbendazim falls into the more serious Category 1 classification
14
Challenges Faced by a Coatings Formulator:
Consumer perceptions about label warnings

Challenges for a coatings formulator




Limited number of available biocide active agents
Concern about consumer perceptions opposite label warnings
Fungicides with low water solubility; Carbendazim, Chlorothalonil,
Zinc Omadine™
Chlorothalonil


Pluses
 Very low water solubility
 Good anti-fungal spectrum plus some activity against algae
Minuses
 Alkaline pH hydrolysis
 Problematic compatibility history with other paint ingredients; pinking, yellowing
 Chalking in colored paints
 Very limited activity against bacteria
 CLP / GHS labeling for Chlorothalonil – Health Hazard + Environmental Impact
 Chlorothalonil is in IARC Group B2 => GHS Category 2
 Cat 2 ≥ 0.1% but <1.0% “Some authorities will chose to label…others would not
normally require a label”
 Cat 2 ≥ 1.0% “a label would generally be expected”
Under GHS, Chlorothalonil falls into the less serious Category 2 classification
15
Challenges Faced by a Coatings Formulator:
Consumer perceptions about label warnings

Challenges for a coatings formulator




Limited number of available biocide active agents
Concern about paint compatibility and consumer perceptions
opposite label warnings
Need a fungicide with low water solubility; Carbendazim,
Chlorothalonil, Zinc Omadine™
Zinc Omadine™

Pluses
 Broad spectrum; Anti-fungal, Anti-algal, Anti-bacterial
 Zinc Omadine™ ZOE formulation has good compatibility history with other paint
ingredients
 CLP / GHS labeling
 Zinc Omadine™….

is not a mutagen, is not a carcinogen, is not a skin sensitizer
 EU CLP Labeling only for Environmental Impact
• For ZOE, the EU threshold limit for labeling (6000 ppm ZOE)
is above the typical ZOE use level

Minuses
 Requires suppression of trans-chelation
16
Zinc Omadine™ ZOE Dispersion
EU Labeling Requirements
Concentration %
Classification
0.1 - 0.6
R52/53
0.6 - 1.0
N; R51/53
1.0 - 2.5
N; R51/53
2.5 - 10.0
N; R50/53
N = Dead fish and tree
R50/53 : Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
R51/53: Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment
R52/53 Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment
Zinc Omadine™ does not require health hazard labels,
it requires environmental hazard labels only at ZOE dosages above 6000 ppm,
and only in regions where environmental hazard labeling is required
17
Challenges Faced by a Coatings Formulator:
Consumer perceptions about label warnings

Challenges for a coatings formulator
 Limited number of available biocide active agents
 Select Zinc Omadine™ as low solubility active agent for durable protection of the paint
film
 Need a supplemental algaecide?
 In many situations Zinc Omadine™ alone has sufficient anti-algal activity
 However, panel testing shows some situations where a supplemental algaecide helps
 Available supplemental algaecides; Diuron, Irgarol™, Terbutryn



Consider cost effect – Diuron offers good value
Consider spectrum – Diuron contributes to anti-fungal activity
Consider CLP / GHS label
 All algaecides will have Environmental Impact
 Diuron – Health Hazard + Environmental Impact
 Diuron is EU Category 3 => GHS Category 2



Cat 2 ≥ 0.1% <1.0% “Some authorities will chose to label…others would not normally require a label”
Cat 2 ≥ 1.0% “a label would generally be expected”
On balance, Diuron is preferred
Under GHS, Diuron falls into the less serious Category 2 classification
18
Challenges Faced by a Coatings Formulator:
Developing a strategy for dry film protection

Challenges for a coatings formulator

Limited number of available biocide active agents

Select Zinc Omadine™ as durable fungicide + Diuron as supplemental algaecide

Benefits from a co-fungicide with higher water solubility; OIT or BBIT or IPBC ?

Look at active combinations, and active ratios

DS 6337, DS 6338: Zinc Omadine™ + Diuron + OIT (Isocil™ WT Fungicide)



DS 6338 alt.:
Zinc Omadine™ + Diuron + BBIT (Densil™ DN Antimicrobial)
DS 6372, DS 6373: Zinc Omadine™ + Diuron + IPBC (Omacide™ Fungicides)
Test under different conditions

Different paint types, Different substrates, Different exposure conditions

Consider cost effect

Evaluate overall performance

Zinc Omadine™ + Diuron + OIT performs better overall than the other two combinations

DS 6338 (with OIT) was the best performing ratio of these active agents => Densil™ ZOD

Formulating Densil™ ZOD with OIT concentrate avoids introduction of VOC
19
Panel Study – Experimental Design

Problem



Background








Panel studies conducted in multiple regions – Project Bristle
Substrates, painting practices, etc. selected as appropriate for each region
Zinc Omadine™ as foundation, vary secondary algaecide inclusion, vary co-fungicides
Findings


Durable film protection in geographical areas with high algal pressure
Identify biocide options consistent with local regulatory environment
Need different secondary algaecide or different co-fungicide for different global regions
Need different active agent ratios for different global regions
Results
Commercialize DS 6338 as Densil™ ZOD as a global product
Commercialize DS 6408 as Densil™ FAZ (alt. ratio; ZnOM/OIT/Diuron) for Asia
Commercialize other products for other regions
US Test Site
EU Test Site
India Test Site
S. Asia Test Site
20
Panel Study – Active Agents

Lonza’s biocide offerings for dry film protection



Broad spectrum antimicrobials
Durable film protection
Biocide formulations optimized for use in coatings
Active
Agent
Biocide Product
Active
Agent
Biocide Product
ZnOM
Zinc Omadine™ ZOE Antimicrobial
OIT
Isocil™ WT Fungicide
Zinc Omadine™ Powder Antimicrobial
IPBC
Omacide™ IPBC 40 Fungicide
CLT
Zinc Omadine™ FPS Antimicrobial
Omacide™ IPBC 30 Fungicide
Densil™ C40 Antimicrobial
Omacide™ IPBC 20 Fungicide
Omacide™ IPBC 100 Fungicide
BBIT
Densil™ DN Antimicrobial
Densil™ DG45 Antimicrobial
21
Panel Study – Zinc Omadine™ Formulation

Zinc Omadine™ ZOE Antimicrobial


Zinc Omadine™ provides durable dry film protection against both fungi and algae
Advantages of Zinc Omadine™ ZOE Antimicrobial

Biocide formulation optimized for use in coatings

The ZOE formulation has good compatibility history with other paint ingredients

The ZOE formulation contains proprietary Lonza technology to suppress Zinc Omadine™
trans-chelation

Broad range of pH stability; Excellent thermal stability

Zero VOC

Can be used for both Interior and Exterior paints


Interior paints are increasingly being rated for mold resistance

Zinc Omadine™ is familiar to consumers as the world’s leading anti-dandruff agent

Well established track record of safety in skin contact applications
Compliant with upcoming regulations

EU CLP trigger concentration for Environmental Hazard label above typical use level

No anticipated Health Hazard labeling post U.S. GHS implementation
22
Panel Study - Test Fence Results Summary
North Vertical Wood - Flat- 12 Months
10
9
8
7
6
Rating
10
9
8
6
4
2
0
Description
No Fungal Growth
Trace
Slight
Moderate
Pronounced
Severe
Complete Coverage
5
4
3
Low Dosage
Medium Dosage
2
High Dosage
1
0
23
Panel Study - Test Fence Results Summary
North Vertical HP - Flat- 24 Months
10.0
9.0
8.0
7.0
6.0
Rating
10
9
8
6
4
2
0
Description
No Fungal Growth
Trace
Slight
Moderate
Pronounced
Severe
Complete Coverage
5.0
4.0
3.0
Low Dosage
Medium Dosage
2.0
High Dosage
1.0
0.0
24
Panel Study - Test Fence Results Photographs
Panel Photos from S. Florida Test Fence



Lab made standard acrylic flat paint
BLANK
Primed southern yellow pine
NEG CTRL
AVG = 4.6
Exposure 90 North vertical
34 MONTHS
Photos were
taken at
33 months
Ratings
shown are
for 34 months
DENSIL™ ZOD
DS 6338
3 ACTIVE BLEND
MID DOSAGE
AVG = 7.0
34 MONTHS
DS 6386
2 ACTIVE BLEND
MID DOSAGE
AVG = 6.0
34 MONTHS
POS CTRL
MID DOSAGE
AVG = 4.9
34 MONTHS
DS 6338 alt.
3 ACTIVE BLEND
MID DOSAGE
AVG = 7.0
34 MONTHS
Rating
10
9
8
6
4
2
0
Description
No Fungal Growth
Trace
Slight
Moderate
Pronounced
Severe
Complete Coverage
25
New Products from Panel Study

Introducing - Densil™ ZOD Antimicrobial


Three active dry film biocide blend for exterior coatings

Zinc Omadine™ as the durable less water soluble fungicide

OIT as the more water soluble co-fungicide

Diuron as the supplemental algaecide
EPA reg. # 1258-1345


Use patterns: Paints and Stains, Masonry Coatings, Plasters, Caulks and Sealants, Stucco,
Mastics, and Joint Cements
Advantages of Densil™ ZOD Antimicrobial

Combination of fungicides with different water solubility gives more robust paint film protection

Fungicide blend with secondary algaecide covers a broader range of coating scenarios

Biocide formulation optimized for use in coatings

Densil™ ZOD contains proprietary Lonza technology to suppress Zinc Omadine™ trans-chelation

Zero VOC

Expected to be compliant with upcoming U.S. regulations

Health Hazard labeling post U.S. GHS implementation expected to be above typical Densil ZOD use levels
26
New Products from Panel Study

Introducing - Densil™ FAZ Antimicrobial

Designed for use in high volume paints

Three active dry film biocide blend for exterior coatings

Proportions of active agents differs from Densil ZOD

Densil FAZ has higher ratio of Diuron / (Zinc Omadine™ + OIT)

Consider the impact of geography and climate



Some tropical environments have very high algal pressure

The concentration of algaecide needed may determine the overall biocide dosage required
Having different ratios available provides flexibility for variations in climate and paint formulation
Advantages of Densil™ FAZ Antimicrobial

Combination of fungicides with different water solubility gives more robust paint film protection

Fungicide blend with secondary algaecide covers a broader range of coating scenarios

Biocide formulation optimized for use in coatings


Densil™ FAZ contains proprietary Lonza technology to suppress Zinc Omadine™ trans-chelation
Zero VOC
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Summary – Lonza Support

Lonza’s biocide offerings for dry film protection

Support from Lonza

Corporate level commitment to continual improvement in EHS areas

Strong global regulatory and toxicology expertise and support

Strong microbiological and analytical chemistry support
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Newly opened Innovation Center in Alpharetta, Georgia
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On-going exploration of leading edge technologies

Strong corporate focus on Material Protection and Industrial Solutions

Development of products that are consistent with current requirements
but are also aligned with trends and anticipated future market needs
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Thank You!