“Formulation

Formulation Approaches to
Manipulation of Leaf Uptake””

Dr David Stock
Weed Control Research Biology*
S
Syngenta,
t JJealotts
l tt Hill IInternational
t ti lRResearch
hCCentre.
t

* Formerly;- Formulation Technology Group [email protected]

Contents

● Biodelivery – what do we understand?

● Adjuvants for enhanced delivery.

● Uptake
U t k routes
t – manipulation
i l ti approaches.
h

● Chemical behaviour of adjuvants

j – fate p
processes.

● Factors influencing Formulation approaches.

● Search for “greener” inerts.

2
The complexity of Bio-delivery

Active Ingredient
g

Formulation

3
 Formulation design for activity – What do we know?

Plant uptake Lipo.

Spray modification
Plant uptake Hydro
Fungal uptake Retention aids
I
Insect
t uptake
t k

Rainfastness / Spreaders
stickers
UV Protection

4
Challenges of Crop Protection delivery
● Right amount of compound

● Right place.
place

● Right time

● Optrimised system;-

- Effective “biodelivery”

● Non optimised system;-

- Pollution

- Chemical wastage.

5
Use of adjuvant technology

● Old view (“conventional wisdom”)

- Act as “wetters”
wetters . Early uses relate to soap solutions with copper salt
fungicides

● Current reality

- To overcome biodelivery issues inherent in the active ingredient.

- Active ingredients must ultimately reach the target and dissolve in

the organism to reach the site.

- Most active ingredients have physicochemical issues which require

formulation/adjuvancy techniques to maximise potential.

- Issues include melting point & solubility, vapour loss.

6
 Adjuvant terminology

● Terminology around tank-mix adjuvants can be very confusing, especially as many

adjuvants have dual functionality.

● Definitions can vary between countries. For example in the UK the following definition is
used by CRD (Chemical Regulations Directorate), according to EU legislation;-

Definition of an 'Adjuvant'
Under Article 2 Scope (3d) of 1107/2009 an adjuvant is defined as:
‘substances or preparations which consist of co-formulants or preparations containing
one or more co-formulants, in the form in which they are supplied to the user and placed
on the market to be mixed by the user with a plant protection product and which enhance
its effectiveness or other pesticidal properties
properties, referred to as ‘adjuvants’
‘adjuvants’.

● For the USA there is a much more extensive list of terminology via the American Society for
Testing and Materials Standards (ATSM).

7
Main chemical types of tank-mix adjuvants

Chemistry Examples Mode(s) of action

Organic surfactants (ionic and nonionic) Agral, Ethokem Enhanced foliar retention
i
increased
d penetration,
t ti coverage

Organosilicone surfactants Silwet L-77, Sylgard 309, Enhanced foliar coverage,

Break-Thru S240 stomatal flooding,
g, enhanced
rainfastness

Oils (mineral, vegetable, trans-esterified Codacide , Actirob B Enhanced coverage, foliar

vegetable) penetration, increased
availability of a.i.
a i (insecticides)

Terpene derivatives (polymer forming NuFilm Increased resistance of foliar

compounds) deposits to washoff. Volatility
reduction.
reduction

Polymers (polyacrylamide, Atlas Companion, Polycote Reduced droplet drift, enhanced

polyvinylalcohol) and synthetic latex Polymer foliar retention

Inorganic salts Ammonium sulphate Increased penetration

(overcoming antagonism by
divalent cations)

8
Historic changes in adjuvant chemistry

1970 1980 1990 2000 2010 2020

Commodity surfactants – e.g.

e g NPEs
Banned
Simple Oils
Minearl oils being replaced by natural products
APGs
Mainly glyphosate use

Complex oil blends

Organosilicone surfactants

Pinoxaden adjuvant
Syngenta introduction

New Chemistry

9
 Adjuvant Mode of Action;-

Addressing the Delivery Challenge

10
Adjuvants are chemicals !

● Adjuvants have modes of action which, like pesticide active ingredients,

is determined by their chemistry!

● NIS = No Information Supplied

(D Stock & G Briggs, WSSA Adjuvant Symposium, Toronto 2000)

● It is important to know adjuvant fate and the kinetics of the processes

involved.

11
 Why do we need adjuvants?

● Optimised delivery to the target site (environment benefits)

- Maximising the dose which reaches the site of action.
- Minimising loss processes to the environment
environment.
- Rain washing
- Lack of foliar retention
● Minimising dose requirement of the AI
- Reduced manufacturing, packaging.
- Cost reduction.

12
How to select the most appropriate adjuvant;-
● It depends on;-
- What is the delivery problem with the formulated product?;-

- Uptake

- Coverage

- Retention

- Rainfastness

● Mode
M d off action
ti studies
t di and
d Biokinetic
Bi ki ti investigations
i ti ti ffor th
the A
Active
ti IIngredient
di t should
h ld
provide key information on;-

- Where is the AI needed ((surface/contact activity,

y systemic
y etc)?
)

- Uptake rate and likely loss to rainfastness or UV degradation.

- Is coverage an issue (vapour redistribution may compensate for poor coverage, e.g.
pirimicarb).

● Based on such considerations, there is no such thing as a “good” general adjuvant.

13
Spreading:- Retention / wetting /spreading

Good foliar spreading

Good wetting properties

needed to ensure spreading
across rough leaf surfaces

Foliar retention a priority

14
Foliar retention:- Impaction and retention process

5ms

Typically
100ms

•Droplet impaction/ retention process highly complex

complex,
-may retain on initial impact
-mayy bounce one or more times then retain
-may bounce off
-may shatter
•Retention occurs when adhesion energy + energy dissipated
during impaction is greater than kinetic energy of impaction

15
Foliar retention:- Important parameters

•Process is dependent on
-droplet size ((most material is in the large
g droplets that
retain the least readily)
-droplet velocity
•Timescale
Timescale of the process may be as small as 1ms.

•Amount retained may be correlated to two spray liquid properties

Dynamic Surface Tension

-a low DST allows droplet to wet surface, increases
adhesion and displaces air from between droplet/ leaf
Extensional viscosity
high viscosity dissipates energy during process

16
 Foliar retention:- Dynamic Surface Tension

air Surfactant diffuses to surface

surfactant solution
t=0, =water long time, =e

 Increasing
concentration

1 10 100 1000 surface age/ ms

•Retention can be correlated to DST at a surface age of 40ms

17
 Foliar retention:- Comparison of retention on glasshouse
and outdoor g grown HORVS

1.4
Outdoor sept 2000
Glasshouse feb 2000 Addition of a good
1.2
Glasshouse jely 1999 retention aid has
1.0
smaller effect on
on
Norm alis ed retentio

outdoor plants
0.8

Norm. ret.
0.6
water
OD 0.47
0.4
GH
G 0.12
0
0.2

00
0.0
35 40 45 50 55 60 65 70 75

 40ms/m Nm
-1

Retention aid increases retention cf water by factor of 8 in GH

but only by 2 on OD
18
Foliar retention: SEM pictures of abraded wax on outdoor
grown HORVS

C t lli wax
Crystalline

Surfactant/glyphosate
Abraded wax
Adaxial surface-abraded wax easier to wet than undisturbed crystalline wax
19
Spreading of oils on wheat (applied as emulsions)
0 2µl droplets with 0
0.2µl 0.5%
5% emulsions EW applied to wheat in 25%v/v
isopropanol, spread areas determined 2HAT
Lower magnification than other image

Wheat with 0.5% methylated rapeseed oil Wheat with 0.5% castor oil EW
EW
Treatment (emulsions in Average spread area on
water) wheat (mm2)
0.5% methylated rapeseed oil 4.96 +/- 1.08

0 5% rapeseed oil
0.5% 2 31 +/
2.31 +/- 0.57
0 57
0.5% castor oil 0.65 +/- 0.11
20
 Microscopy of leaf surfaces
FESEM images
g of adaxial surfaces of leaves with varying
y g degrees
g of microroughness
g

Wheat Maize Sugar

g beet

Pea Strawberry Vine

Difficult to wet Easy to wet

21
 The Challenges of Foliar Uptake

22
The Cuticle:- Barrier to Penetration

outer layer between aerial plant parts and their environment:

• stabilises tissues
epicuticular waxes
cuticular proper • protection
t ti against
i t
cuticular layer outer influences
pectin lamella
cell wall i i i
• minimises l hi off
leaching
nutrients

• habitat for
microorganisms

• transpiration
t i ti barrier
b i

23
Physicochemical Window of Crop protection Compounds

Property Range

Melting Point -20OC to >250OC

M l
Molecular
l weight
i ht 160 tto 1000

Organic solubility Negligible to Miscible

Aqueous solubility Negligible to 1005g/l

Log P (octanol / water partition -3

3 to >6
6
coefficient

Vapour Pressure mPa to non-volatile

24
 Choice of Methods

Transport through cuticles

Reconstituted waxes

Uptake/Desorption from cuticles

Modelling

Uptake
p into leaves
Biological efficacy
Confocal Microscopy

25
Hydrophilic uptake routes & adjuvancy

e -18
e -19 1
2 1 Water
e -20
20 2 Eth
Ethanoll
3 Erythrose
e -21 3 4 Benzoic acid
e -22 5 Xylose
e -23 5 6 Glucose
7 2,4-D
2,4 D
e -24 8 Salicylic acid
e -25
K) [m/s]

4 9 Maltose
e -26 6 10 Maltotriose
78
e -27
ln (P/K

e -28
e -29 10 -5
10 -6

e -30 10 -7 Erythrose

e -31
10 -8
10 -9
9
Ethanol
m/s]

Water Xylose

e -32
32 -10
log P [m

10
10 -11 Glucose

e -33 10 -12
10 -13 Maltose
10
e -34
-14
10 Maltotriose

10 -15

e -35 10 -16
0 50 100 150 200 250 300 350

e -36
36 Molar volume [cm³/mol]
[cm /mol]

0 50 100 150 200 250 300 350

Molar volume [cm³/mol]
[cm /mol]
C Popp et al. (2005). Journal of Experimental Botany, Vol 56, Nol 421, pp2797-2806)
26
 Humectancy

● Humectants hold onto water which helps to keep water-soluble active

ingredients in a liquid form suitable for foliar uptake.

- There is now good evidence that hydrophilic channels pass through

the leaf cuticle. Maintaining water soluble materials in a liquid form
enhances access to such channels.

● Humectants are only effective if the Relative Humidity is above a critical

value (varies between different humectants).

● Numerous types
yp of chemicals act as humectants;-
;

- Glycerol

- Sugars

27
Humectancy (2);- Example of 2 paraquat deposits at 50% RH

Sodium chloride Monoethanolamine chloride

28
Development of a Predictive Uptake Model to Rationalise
Selection of Polyoxyethylene Surfactant Adjuvants for
F li
Foliage-applied
li d Agrochemicals
A h i l

29 Stock et al, Pestic.Sci, 1993, 37, 233-245

Interrelationship between surfactant and AI
physicochemical properties during foliar penetration
● A qualitative model is available for nonionic ethoxylates
g
- Higher ethoxylates
y preferred for water soluble, low log
g P, compounds
- Ethoxylation is less important for intermediate log P compounds
- Lower ethoxylates optimal for high log P compounds
● Superficial relationship to HLB within a surfactant series
- Use of this surfactant parameter is meaningless in isolation.
● No unified penetration-enhancement mechanism is implied
- More recent studies on cuticles has provided valuable information to
understand penetration mechanisms and adjuvant impact.
● Optimal structures for penetration not necessarily ideal for other key
adjuvancy processes.

30
31
Diiffusion Co
oefficient D
Dx1016 [m2s-1]

Em
1000

100

1
10
ul PL
so
g S
en
EL
36

G SD
af
ac S
Ra RE
pe 61
Se 0
ed
O
Si il
Diffusion in Plant Waxes

lw
et
L7
Additive 7
Ac
tip
ro
n
C1
2E
Te 4
rp
M in
eo
et
hy l
lo
Barley wax in the presence of adjuvants

M le
Diffusion coefficients (D) of Clodinafop in

et at
hy e
ll
au
ra
te
Activity on Real Plants
Clodinafop on Alopecurus myosuroides 24 days after application (climate chamber, 6-8°C)

No Adjuvant Rapeseed Oil C12E4 Me-Oleate

(minimalistic formulation)

32
 Stomatal infiltration – organosilicone surfactants

Spray Droplets On Leaf Surface

Without Surfactant Conventional Break-Thru® S 240

72 mN/m Surfactant 26 mN/m
112° Angle 33 mN/m 0° Angle
48° Angle

33
 Volatility t1/2 values for a selection of adjuvants

Hydrocarbon VP VP (mm Volatilisation t 1/2 on leaf

((Pascal)) Hg)
g) ((Kg/ha/day)
g y) for 1 Kg/ha
g
EH 10 400 3 68,000 <<<1 min
EH 15 9 7 x 10 -2 1,400 < 1 min
EH 20 0.1 1 x 10 -3 30 30 min
EH 25 4 x 10 -33 3 x 10 -55 05
0.5 1d day
EH 30 8 x 10 -7 6 x 10 -7 0.01 50 days

Material Equivalent Hydrocarbon

(EH)
C pa
C12 paraffin
a 12
C15 paraffin 15
N-methylpyrrolidone 13
Methyl
y oleate 21
Butyl oleate 24
Triolein >>30
C8E2 19
Briggs, G.G & Bromilow, R.H. (1994). In: Interactions between adjuvants, agrochemicals and target organisms, Proceedings of the
12th34
Schering Foundation Workshop, P.J. Holloway, R.T. Rees & D. Stock (Eds), Springer Verlag. pp 1-26.
 Adjuvant properties and plant surface behaviour
Adjuvant EH Log P  log P % Water Plant uptake Function Predominant
content fate process

Me oleate 22 8 0.2 Zero Rapid Solubiliser Volatilisation,

(Me seed oil) plant
metabolism
Triolein >50 25 0.6 Zero V slow Solubiliser Surface deposit
(seed oil)

NP ethoxylate 35 4.5 3 4 Rapid Solubiliser Plant uptake,

5EO metabolism

NP ethoxylate 50 4 5 14 Medium Solubiliser + Plant uptake,

10EO water metabolism
retention
NP ethoxylate >50 3 9 25 Slow Water Plant uptake,
20EO retention metabolism,
surface deposit
Typical 13-17 7-9 0 Zero Medium Solubiliser + Volatilisation
mineral oil spreader

EP-PO >50 7 V large High Zero Water Surface deposit

((30:70)) retention +
polymer Mr deposit form
4950
PVA 17% >50 >0 V large High Zero Water Surface deposit
acetyl Mr retention +
14000 deposit form
Stock, D. & Briggs, G.G. (2000). Physicochemical properties of adjuvants; values and applications. Weed Technology, 14, 798-806.

35
Ambient temperature FESEM images of controlled evaporation tralkoxydim formulations sprayed at 120g ai/ha onto AVEFA plants
Grasp Standard SC : 109296 (Treatment 20)
< 8 HAT

36
Ambient temperature FESEM images of controlled evaporation tralkoxydim formulations sprayed at 120g ai/ha onto AVEFA plants
Grasp Standard SC : 109296 (Treatment 20)
1 DAT

37
 Examples of Activity Improvement

38
 Pinoxaden
No wetting
g ((No Retention aid,, No adjuvants)
j )
% Control

100
90
80
70
60
50
40
30
20
10
0
Avena Lolium Alopecurus
p Setaria
Pinoxaden.. Average of 3 rates (4, 8 & 16g/ha)

39
 Pinoxaden
Good Wetting
g ((Retention aid,, No adjuvant)
j )
% Control

100
90
80
70
60
50
40
30
20
10
0
Avena Lolium Alopecurus
p Setaria
Pinoxaden.. Average of 3 rates (4, 8 & 16g/ha)

40
 Pinoxaden
Wetting
g + Adjuvancy
j y ((Retention aid + Novel adjuvant)
j )
% Control

100
90
80
70
60
50
40
30
20
10
0
Avena Lolium Alopecurus
p Setaria
Pinoxaden.. Average of 3 rates (4, 8 & 16g/ha)

41
Adjuvancy: the “on-off“ switch for pinoxaden

 The adjuvant increases uptake and performance of pinoxaden

 Uptake is primarily through leaves
 Necrosis and death of green tissue within 2-5 weeks

42
Impact of a range of adjuvants on uptake of pinoxaden into
wild oat leaves.

43
Impact of adjuvants on mobility of pinoxaden
60°
-31.5 50°C 40°C 33°C 20°C 10°C
n (D) [m2s-1]

-33 5
-33.5

-35.5
sion coeffficient ln

-37.5

39 5
-39.5
No Adjuvant
-41.5
Diffus

Rape Seed Oil

-43.5
Me-Oleate
-45.5
45 5
3 3.1 3.2 3.3 3.4 3.5 3.6
Reciprocal Temperature (1/T) * 1000 [K-1]

44
Rainfastness; Comparison of BRAVO® vs. competition

The scanning electron micrographs illustrate the difference in deposits of BRAVO®

and competitor after 127 mm of simulated rain. Note that although the deposits of both
products appear similar prior to rain (top row), only the BRAVO® deposit is clearly
distinguishable after 127 mm of rain (bottom row).

BRAVO® Competitor
Scanning electron
micrographs of BRAVO®
and competitor on the surface of No rain

cantaloupe leaves
before (no rain) and after 127 mm
of simulated rain.

127 mm rain

45
 Practical considerations in Adjuvant
Adj ant chemistr
chemistry

46
 Impact of some penetration enhancers on sensitive plant
species

Control Adjuvant based formulation

47
Phytotoxicity from Surfactants

● Surfactant toxicity to plants has been demonstrated in different ways

including:
- Suppression of leaf growth
- Induction of cellular necrosis on leaves
- Fl
Flower and
d ffruitit abscission
b i i
- Root development

● Surfactant toxicity can have deleterious effects on the translocation of

pesticides in the tissue beneath the spray deposit.

● The most common mechanism identified is surfactant disruption /

solubilisation of biological membranes

48
How will the choice of surfactant influence phytotoxicity?

● Only a few generalisations can be made (from studies in literature):

Cationics>Anionic>/=Nonionic
Lower phytotoxicity

Increasing hydrophobe size

High
g EO content for nonionics
(Increasing MW)

49
Classification: INTERNAL USE ONLY
 Nonionic surfactants

● For alcohol ethoxylate surfactants, membrane disruption potential

typically follows a parabolic relationship
relationship.

Maximum disruption of lipid bilayers

Phy
ytotoxicity

10
EO Chain
Ch i length
l th

50
 Cont…

● Significant differences seen between membrane disruption studies and

whole plant visual assays

- Short chain ethoxylates show higher level damage;- they can rapidly
penetrate the leaf cuticle!

- High plant species variability in ability to metabolise/conjugate

surfactants

51
 Build-In Versus Tank-Mix

● Technical Considerations.

- Physical & Chemical Compatibility.

- Space within the formulation.

● Regulatory Considerations.

- (Will address later in presentation).

● End user considerations & flexibility

- Different acceptance levels according to market segment;- e.g. Common

practice to tank-mix adjuvants with many herbicides..

- Built-in products have a fixed adjuvant:AI ratio;- potential issues for reduced
dose application and in high volume applications.

52
 Build-in adjuvant approaches.

● High surfactant loaded aqueous formulations.

- SL Formulations (e.g. Touchdown, glyphosate products).

- Aqueous SC formulations (Amistar, azoxystrobin formulations).

● So
Solvent
e t based formulations.
o u at o s

- EC based formulation (Fusilade Max/Forte, fluazifop P butyl).

● Oil based formulations.

- OD formulations (OTeq, ODesi brand formulations, Bayer

Cropscience)

53
Spatial consideration – is there room in the formulation?

54
 Other formulation considerations

● Physical compatibility & handing

● Chemical compatibility issues;- adjuvant and Active Ingredient

Finely dispersed
particles
5 microns

Dramatic crystal growth

200 microns

55
Use of OD technology to balance requirements

56
 OD: solution to a physical compatibility challenge


57 Classification: PUBLIC
 Built-in next generation....

Novel Adigor Competitor

(0.125%) (0.5%) (0.5%)

58
 “Inert” Regulations

59
Regulatory situation of Adjuvants / Inerts
● Significant differences between EU and USA
- REACH regulations impact current EU trends.
- USA situation complicated by in-can versus tank-mix adjuvants.
- Tank-mix adjuvants do not need to comprise EPA approved Inerts.

● Regulatory consideration will be a significant driver in terms of new

chemistry and commercial strategy.
- Environmentally “friendly” adjuvants.
● Pesticide sales often underpinned by adjuvant chemistries of modest
commercial value to suppliers.
- Major uses of current adjuvant chemistries often driven by other
industries.
- [Use of tank-mix adjuvants often destructive in terms of commercial
i
impact.]
t]

60
Core Data Requirements

● Product Chemistry
● Structural Activity Relationship
● Acute Toxicity (6 Pack)
● Genotoxicity (Ames +)
● One Generation Repro Screening Test (OECD 422)
● Biodegredation
● Ecotox (daphnia, fish)
● Risk Assessment
● Additional Data May Be Needed
- up to full A.I. package

- Endocrine Effects (a particular issue for some Inerts)

61
 Identification of new solvent tools

● Various new solvents and cosolvents promoted within the Ag industry.

- Propylene carbonate. (e.g. Huntsman).

- Short chain fatty acid esters.

od aso ® Polarclean
- Rhodiasolv® o a c ea ((Vidal al,, 9th International
da et a te at o a SySymposium
pos u oon
Adjuvants for Agrochemicals)

- Dimethyl lactamide.
lactamide

- Based on natural materials processed within Biochemical systems of mammalian

system.
t

62
 Cont

Improvements in or relating to pesticide formulations with lactamides. Bell, Gordon Alastair; Harris,
Clair Louise; Tovey, Ian David. (Syngenta Limited, UK). PCT Int. Appl. (2009), 21pp. CODEN:
PIXXD2 WO 2009027624 A2
Improvements in or relating to organic compounds used in agrochemical formulations. Bell, Gordon
Alastair; Harris, Clair Louise; Tovey, Ian David. (Syngenta Limited, UK). PCT Int. Appl. (2009),
Preparation of lactamides as agents for reducing the toxicity of pesticides. Bell, Gordon Alastair;
Tovey,
y, Ian David. ((Syngenta
y g Limited,, UK).
) PCT Int. Appl.
pp ((2007),), 19 pp
pp. CODEN:
PIXXD2 WO 2007107745 A2

63
 Skin function test for surfactants

64
 Safening effect of dimethyl lactamide

65
How do you choose the “best” delivery system ?

● It depends!....

● What are the problems to be

addressed?

● What is acceptable in terms of

a Product Strategy?
gy

● Need to consider other trends

- Regulatory

- Market preference.

66
Acknowledgements

● Phil Taylor

● Gordon Bell

● Christian Popp

● Adrian Friedmann

● Gill Foundling

● Ian Shirley

67
......where are we going?......

1970 1980 1990 2000 2010 2020

Commodity surfactants – e.g.

e g NPEs
Banned
Simple Oils
Mineral oils being replaced by natural products
APGs
Mainly glyphosate use

Complex oil blends

Organosilicone surfactants

Pinoxaden adjuvant
Syngenta introduction

New Chemistry

68
What will the changes be?

● There will/must be some!

● Changes
Ch are already
l d underway.
d

- Some are Regulatory driven (see next section).

- Others are technical or market-driven in terms of in-can development.

- E.g. Introduction by Bayer of Oil-Dispersion formulations (OTeq, ODesi).

● Patenting activity competitive as this is a key aspect of portfolio defence

defence.

69
 Non-target effects: direct impact on phtytotoxicity.

● Surfactant-type adjuvants

- Cationics>Anionic>/=Nonionic
Cationics>Anionic>/ Nonionic

● Ionic surfactants

- Phytotoxic effects often not well understood

- Charge interaction with membrane proteins considered a key factor

(disruption of folding impacting on functionality)

- Note:- SDS surfactant (sodium dodecyl sulphate) is used in gel-

electrophoresis for proteins for this reason!

70
 Data Package Generation
● Search of Public Data Bases, MSDS, etc.

● Conduct Studies to Fill Gaps

71
Regulatory data requirements: EU

Country Toxicology Efficacy Residues

Austria Y Y N
Belgium Y Y N
Denmark N Y N
Finland N N N
F
France Y Y N
Greece Y Y N
Germany Y Y Y
Ireland Y N N
Italy Y Y Y
Netherlands N N N
Portugal Y N N
Spain Y Y Y
Sweden N N N
UK Y N N/Y
(Butselaar & Newman, 1998)
...not much harmonisation yet!

72
General comments
● Globally there is increasing regulatory concern regarding the non-target environmental
effects of “inerts” including adjuvants.

- Oestrogenic effects of Nonylphenol ethoxylates (NPEs).

- Loss of NPE emulsifiers and the Agral tank-mix adjuvant from the Syngenta
range.

- Amine ethoxylate surfactants an increasing issue in EU, especially Germany;-

- Tallow amine ethoxylates classically used with original glyphosate formulations

have ecotox. issues in terms of effects in aquatic systems.

73