Report on E171 (titanium dioxide) and

E172 (iron oxide) - analytical

perspectives from research

Submitted on behalf of TDMA & TC E172

1./2. April 2019 Parma

Report on E171 (titanium dioxide) and E172

(iron oxide) - analytical perspectives from

research

2

Five E171 grades were analysed by

SEM, BET, Brookhaven XDC and

CPS DC

25 E172 grades were analysed by

SEM, TEM, BET, Brookhaven XDC

and LD

Yellow 3

Red 2

Red 11

Black 1

Sample BSample A

Sample C Sample D

Sample E Product Name Colour Crystal Phase

Yellow 3 Yellow Goethite FeO(OH)

Red 2 Red Hematite Fe2O3

Red 11 Red Hematite Fe2O3

Black 1 Black Magnetite Fe3O4

Sample Anatase (%)

A 99,9

B 99,7

C 99,6

D 99,1

E 99,4

SEM results E171

E171 is not a nano product

3

• SD low for E171 Manufacturer (M1, M2, M3)

• Inexperienced laboratories could find very different results

A B C D E

M-1 SEM 0.137 0.105 0.115 0.163 0.106

M-2 SEM 0.140 0.101 0.110 0.173 0.102

M-3 SEM 0.138 0.108 0.113 0.162 0.105

0.000

0.050

0.100

0.150

0.200

0.250

med

ian

x50

(µ

m)

A B C D E

M-1 SEM 18 46 36 10 44

M-2 SEM 18 50 37 10 47

M-3 SEM 19 41 36 14 44

0

10

20

30

40

50

60

Q0<

10

0n

m (

%)

A B C D E

LAB A SEM 4 5 3 0 22

LAB A STEM 12 12 19 7 42

LAB B TEM 29 55 41 15 59

0

10

20

30

40

50

60

Q0

<10

0n

m (

%)

A B C D E

LAB A SEM 0.179 0.162 0.165 0.222 0.142

LAB A STEM 0.145 0.145 0.126 0.183 0.12

LAB B TEM 0.127 0.095 0.109 0.164 0.095

0.000

0.050

0.100

0.150

0.200

0.250

med

ian

x5

0 (

µm

)

4

Correlation x50 with dminVSSA highTEM vs BET

0%

20%

40%

60%

80%

100%

0

100

200

300

400

500

600

700

800

Yellow 1

Frequency Cumulative %

0%

20%

40%

60%

80%

100%

0

20

40

60

80

100

Red 11

Frequency Cumulative %

0%

20%

40%

60%

80%

100%

0

50

100

150

200

250

300

Red 2

Frequency Cumulative %

• VENATOR is the sole manufacturer

of E172

• Primary particle size analysis

possible for red and yellow but not

for black Iron Oxides

• Rubout of crystals in a monolayer on

the surface is important for accurate

results

• Will be difficult to find an external lab

which is able to measure Iron Oxides

• High correlation with dminVSSA

y = 0.945x - 0.0049R² = 0.9975

y = 1.0082x + 0.0047R² = 0.9865

0.01

0.1

1

0.010 0.100 1.000

x50 (

µm

)

dminVSSA (µm)

x50 feret.min vs dminVSSA

x50 ECD vs dminVSSA

Linear (x50 feret.min vs dminVSSA)

Linear (x50 ECD vs dminVSSA)

Particle Size for Risk Assessment?

We support the EFSA approach to analyse the particle size of food additives

as pristine material, in the food matrix and in biological media

However, the guidance document is not consistent on page 21 in the

evaluation of agglomeration or aggregation state by two independent

methods

Standard EM can only measure the constituent particles size and not the

agglomeration or aggregation state

The second method must corelate with EM to be a suitable screening

method and the sample must be dispersed to a plateau

Nevertheless, for many products (Black Iron Oxides) EM doesn’t work and

alternatives must be possible

The Nano Define decision-flow scheme for dispersion criteria on page 79

should be adjusted by the dispersion technique and mandatory correlation

with EM

Constituent Particles

5

Mobile Particle Size for Risk Assessment

“Once a material is classified as nano according the constituent particle

size of the EU definition, the information on the mobile particle size under

realistic conditions (food matrix, biological media, etc.) is needed.

Dispersability has been reported as a founding base for the grouping of

the nano materials” (EChA, “Appendix R.6-1 for nano materials

applicable to the Guidance on QSARs and Grouping)

The OECD TG318 for aqua toxicity could be a good base for food

application, a defined dispersion energy according to NIST 1200 is

recommended and indicates the particle size in aqueous media

The same issues apply for food, what is the right dispersion energy,

what is the dispersion medium, degradation, dissolution…….

An initial approach for the determination of the E171 and E172 smallest

mobile particle size of the pristine material or in the food matrix is

presented on the next slides

Defined Dispersion Energy

6

Volume weighted Particle SizeStandardised dispersion energy

7

Particle size control of E171 and E172

by a standardised dispersion procedure:

Comparing production dispersion

energy density with laboratory scale

using NIST 1200 TG

The energy density of 240 J/ml is

three times higher than normally

applied in production wet milling of

TiO2

Full redispersion of agglomerates

without breaking up aggregates or

constituent particles

M. Stintz propose 270 J/ml for

synthetic amorphous silica (SAS),

Powder Technology 318 (2017) 451-

458 and Nanomaterials 8 (2018) 454

Aggregate size is determined by the

production process (page 17 line 14)

Not possible to disperse completely to

unbounded constituent particles

Dispersion with low energy

Dis

pers

ion E

nerg

y

0.261 0.2530.328

3.373

0.100

1.000

10.000

Yellow1 Red2 Red11 Black1

Vo

lum

e X

50

(µm

)

E172

8

Volume based particle sizes for risk assessment

Comparison E171/ E172

0.280 0.264 0.2670.369

0.304

0.100

1.000

10.000

A B C D E

Vo

lum

e X

50

(µm

)

E171

0.81.1

0.8

0.1

1.3

0.100

1.000

10.000

A B C D E

Vo

lum

e N

ano

(%

)

E171

“Dispersibility has been reported as a founding base for the grouping of the nano

materials” (EChA, “Appendix R.6-1 for nano materials applicable to the Guidance on

QSARs and Grouping)Brookhaven XDC

Dispersion Energy 240 J/ml5

2

1

0.100

1.000

10.000

Yellow1 Red2 Red11 Black1

Vo

lum

e N

ano

(%

)

E172

9

Conclusion on Particle Size AnalysisE171/ E172

E171 is not a nano material according the EU definition

E172-Black Iron Oxides are not nano products

The dispersion criteria of the Nano-Define decision-flow scheme

shall be corrected for “constituent particles”

Realistic volume based particle sizes for toxicological testing can

be achieved by dispersion energies <300 J/ml

Using the NIST 1200 TG volume based particle sizes of different

products can be easily compared by different laboratories

Implementation of a dispersibility criterium in the risk assessment

CPS DC and Brookhaven XDC are suitable instruments to

measure mobile nano particles

10

Back Up

11

Absolute particle size depends on the method

E172 Particle Size by Brookhaven XDC & LD

Dispersion Energy 240 J/ml

Same trend for both methods

0.236

0.319

0.261

0.145

0.253

0.527

0.1920.220

0.2340.253

0.425

0.493

0.623

0.328

0.640

0.747

0.690

0.500

0.610

0.870

0.580 0.5700.590 0.600

0.6900.717

0.900

0.770

0.000

0.100

0.200

0.300

0.400

0.500

0.600

0.700

0.800

0.900

1.000

Yellow1 Yellow2 Yellow3 Red1 Red2 Red3 Red4 Red5 Red6 Red7 Red8 Red9 Red10 Red11

Geothite Hematite

[µm

]

Average XDC X50 Volume (µm) Average MS2000 X50 Volume (µm)

12

Good sensitivity for high nano contents

E172 Nano Content by XDC & LD

• Brookhaven XDC is more sensitive to fine particles than LD

5.0

3.0

5.0

12.0

2.0

1.0

6.05.7

5.0

1.7

1.0 1.0 1.0 1.01.2

0.1 0.7

8.4

0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00

2

4

6

8

10

12

14

Yellow1 Yellow2 Yellow3 Red1 Red2 Red3 Red4 Red5 Red6 Red7 Red8 Red9 Red10 Red11

Geothite Hematite

[%]

Average XDC Q3 (%) <100nm Averagen MS2000 Q3 (%) <100nm

Long Dispersion experimentNo complete dispersion of aggregates after 3h

13

Anatase 1h Horn Sonication Anatase 2h Horn Sonication Anatase 3h Horn Sonication Some Crystal Debris More Crystal Debris Increased Crystal Debris

Anatase 3h probe sonication

increased tip debris

aggregates still survived

Anatase 2h probe sonication

more tip debris

Anatase 1h probe sonication

some tip debris

3600 J/ml 7200 J/ml 10800 J/ml

E171 Long Dispersion experimentParticle size analysed by CPS DC

14

0.15 0.14 0.14 0.13 0.13 0.13 0.13 0.13 0.12 0.13

23.2 22.928.3 28.5 27.2 30.1 28.9 28.4 31.9 30.2

0.29 0.28 0.27 0.26 0.24 0.24 0.24 0.23 0.23 0.23

1.311.57

1.98 2.26 2.59 2.82 2.88 3.02 3.48 3.28

0.01

0.1

1

10

100

120 300 600 900 1800 3600 5400 7200 9000 10800

2 5 10 15 30 60 90 120 150 180

Dispersion Energy (J/ml) )Dispersion Time (min)

Number Median x50 (µm) Q0.<0,1µm (%) Volume Median x50 (µm) Q3<0,1µm (%)

E171/E171

food

P25

nano

OECD

TG318

SCCS

UV-Filter

SEM number feret.min:

Median x50 = 0,100 µm

Q0<100nm = 47%

SEM number ECD:

Median x50 = 0,120 µm

Q0<100nm = 33%

E171 Brookhaven XDC & CPS DC results

High agreement between different manufacturer

15

A B C D E

M 1 XDC 0.5 0.8 0.3 0.0 1.0

M 2 CPS DC 0.9 1.3 1.1 0.2 1.5

M 1 CPS DC 1.1 1.2 1.0 0.2 1.5

0.0

0.5

1.0

1.5

2.0

Q0<

10

0n

m (

%)

A B C D E

M 1 XDC 0.281 0.260 0.264 0.360 0.301

M 2 CPS DC 0.276 0.264 0.268 0.363 0.310

M 1 CPS DC 0.283 0.269 0.270 0.383 0.301

0.000

0.100

0.200

0.300

0.400

x50

Volu

me (µ

m)

A, 0.280B, 0.264 C, 0.267

D, 0.369

E, 0.304

0.000

0.100

0.200

0.300

0.400

x50 Volume (µm)

A, 0.8

B, 1.1

C, 0.8

D, 0.1

E, 1.3

0.0

0.5

1.0

1.5

2.0

Q3 Volume <100nm (%)

Small interlaboratory SD on volume particle sizes and nano contents

High reproducibility of results

Screening of particle sizes and nano contentsVSSA E172

77.074.3

71.9

91.0

59.8

22.1

76.4

69.2

65.4

61.6

34.2 33.3

21.0

47.5 46.8

72.6

39.0

49.3

43.6

49.6

29.827.3

29.426.9

42.9

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

Ye

llow

1

Ye

llow

2

Ye

llow

3

Re

d1

Red

2

Red

3

Red

4

Red

5

Re

d6

Red

7

Red

8

Red

9

Red

10

Red

11

Bro

wn1

Bro

wn2

Bro

wn3

Bla

ck1

Bla

ck2

Bla

ck3

Bla

ck4

Bla

ck5

Bla

ck6

Bla

ck7

Bla

ck8

Yellow Red Brown Black

VS

SA

(m

2/c

m3)

Cubes&Spheres = 60 m2/cm3

Needles = 40 m2/cm3

Needles & Spheres = 50 m2/cm3

VSSA cut off = 60 𝑚2

𝑐𝑚3 ∗𝐷

3

Smallest dimension D= 3 spheres, 2 needles, 1 flakes

dminVSSA (D*) = 2𝐷

𝑉𝑆𝑆𝐴

BET

According to DIN ISO 9277, samples are heated up to 180°C in 30 min and left at this

temperature for one hour before determination of the SSA under Nitrogen at 5

different pressure ratios: 0,1 – 0,15 – 0,2 – 0,25 – 0,3.

The Volume Specific Surface Area (VSSA) is calculated by multiplication of the SSA

with the gravity ()

VSSA = SSA x Equation 1

The Monodisperse Diameter of the Volume Specific Surface Area (dminVSSA) is

calculated for different particle shapes by the following equation

dminVSSA (D*) = 2𝐷

𝑉𝑆𝑆𝐴Equation 2

The VSSA cut off is calculated by the equation below.

VSSA cut off = 60 𝑚2

𝑐𝑚3 ∗𝐷

3Equation 3

*Smallest dimension D= 3 spheres, 2 needles, 1 flakes

17

Disc Centrifuge and Dispersion

18

Company Instrument Detector Disc Speed Formulation

M-2 CPS DCUV-Light

405nm18000 rpm 0,1g E171, 100 ml water, 0,06 g Calgon N

M-1 Brookhaven XDC X-Ray 3000 rpm 2g E171 in 50 ml water, 0,02 g calgon N

M-1 CPS DCUV-Light

470nm18000 rpm

0,1g E171, 38 ml water, 12g PDO*, 0,05 g

Calgon N

Company Sonic Probe Tip Diameter Tip Length Eglible volume Nominal Power

M-2 Sonoplus 2200 13 mm 250 mm 25-500 ml 750 W

M-1 Sonics VCX750 13 mm 136 mm 25-500 ml 750 W

Dispersion Equipment

Instrumentation, parameters and formulation

NIST 1200 Technichal GuidelinePower Calibration

19