ČTP SusChem
Safety aspects of the nano TiO2
production and application
Presentation at the Nano Safety Conference
Ljubljana 22nd- 24th of April 2009
Antonín Mlčoch
Content
 Preface
 Risk assessment framework of nano TiO2
 Common activities of TDMA
 Ongoing iniciatives
 Relative risk assessment for the several
industrial fabrications of nano TiO2
 Conclusions
 World consumption of TiO2 : ~ 5 mil t/year
 World consumption of UF and nano TiO2 : 40 kt/ year
(including 25 kt /year DeNOx catalysts)
►UF TiO2 has a long history of safe use in cosmetics products spanning
many decades (UV Attenuator )
►Nano TiO2 are also used in catalysts,coatings for self-cleaning
windows,electronics,fotovoltaics and medicine
 Czech Republic – Precheza producer of the pigmentary TiO2
and development of production and application of the precursors for
catalysts , photocatalysts and UV absorbers
3 MARKETS REPRESENT 80% OF
MARKET SHARE
5%
3%
8%
Catalyst
10%
Electroceramic
Color Pigment
UV blockers
54%
Photocatalyst
Misellaneous
20%
40 000 Mt / Year estimated 2006
Spring 2008
The industry is responsible for the evaluation of
any such risks in production and application
► Attention focuses upon the questions of risk assessment and
risk management within the first phase of application research
► Definition and structure of nanomaterials, toxicological and
ecotoxicological behaviour of nanomaterials , exposure and
need for specific ”nanoregulation
I Is the whole life cycle (workers – consumers – disposal to
the environment) under the control by the industry ?

Is there information enough and has the relevant information
distributed adequately?
Potential for exposure to nano TiO2
Risk = Hazard x Exposure
Adapted from Tsuji J.S. § all : Toxicological Sciences;2006 89,
No.1 ,42-50
Routes of exposure, distribution
and degradation of NSP
Adapted from Oberdörster G.: Inhalation Toxicology 2004
Adapted from Oberdörster G.: Inhalation Toxicology 16,2004,23-45
Common activities of TDMA
TDMA Ultrafine TiO2 Working Group : TDMA members + Ishihara,Tayca, Merck
 Assessment of substance risk is time consuming and
costly procedure,multidisciplinary approach.
 Developing of an extensive dossier of safety data and
other evidence which examine the various aspects of the
consumer safety of UF TiO2 → EC Directive : TiO2 is safe
for use in cosmetic products at maximum concentration of
25 % in order to protect the skin
 Standartization of respirable dust measurement
 Review of Toxicology and Epidemiology of TiO2
literature
TDMA = Titanium Dioxide Manufacturers Association
A Sector Group of Cefic
Several basic studies sponsored by TDMA

Historical Cohort Study of Workers Employed in the
Titanium Dioxide Production Industry in Europe, Results of
Mortality Followup; Boffetta, et al; Department of Medical
Epidemiology; Karolinska Institute, Stockholm, Sweden,
January 2003
 Subchronic Inhalation Toxicity Study on Pigmentary Titanium
Dioxide in Mice,Rats ,and Golden Hamsters,
Chemical Industry Institute of Toxicology (CIIT),2002
 Subchronic Inhalation Toxicity Study of Ultrafine Titanium
Dioxide with Mice,Rats,and Golden Hamsters ,CIIT USA 2003
Inhalation Toxicology and
Epidemiology
Subchronic, inhalation study CIIT
Centres for Health Research USA
Rats, mice and hamsters
Photocatalytic TiO2 (Degussa P 25),
Aerosol concentrations of 0,5 , 2 or 10 mg/m3;6 hours/day,13 weeks
Main findings of inhalation study:
There is no evidence that titanium dioxide itself has toxic
properties,that would lead to cancer. This recent study leads us to
believe that titanium dioxide does not present a carcinogenic risk to
man at exposures experienced in the workplace.
►The results of our two mortality studies are most powerful
evidence that UF TiO2 does not have a significant carnigonic
effect on the human lung.
►The studies do not suggest an association between
occupational exposure to TiO2 and risk for cancer.
►Studies on application of sunsreens containing UF TiO2 to
healthy skin revealed that TiO2 particles only penetrate into
the outermost layers of the stratum cornum,suggesting that
healthy skin is an effective barrier to TiO2
►Oral,subcutaneous and intraperitoneal administration did
not produce a significant increase in frequency of any type of
tumor in mice and rats.
Occupational Exposure Limits
NIOSH,USA recommend new exposure limits
of 1.5 mg/m3 for fine and 0.1 mg/m3 ultrafine TiO2
as time weighted average concentrations for up to 10 hr/day during a
40-hours work week.
These levels will serve to minimize any risks that might be
associated with the development of pulmonary inflammation and
cancer.
TDMA opinion : the lower limit for the critical dose of UF TiO2 may
be as high as 2 mg/m3.Hence ,REL of 1,5 mg/m3 would be protective
for ultrafine exposures.
Ongoing iniciatives
 In April, 2008 the European Commission requested additional
information for nanoscaled material in cosmetics especially for TiO2
.The final dossier was submitted to EC 23.2.2009 .
 At the moment WG 4 of ISO Committee is preparing ISO/AWI
11937 Nanotechnologies - Nano-titanium dioxide as a technical
specification, consisting of two parts: characterization and
determination and material specifications of certain applications
(e.g. coatings, cosmetics, plastics, ceramics).
Under WPMN there have been selected 14 nanomaterials for
which data should be gathered. If no data exists, it should be
conducted by testing. Titanium dioxide is one of those substances
selected. TDMA participation and data gathering
WPMN= OECD Working Party on manufactured nanomaterials
UF TiO2 Manufacture and Processing
 The main difference between ultrafine and pigmentary titanium
dioxide is primary particle size.Primary particles form aggregates
and agglomerates.The primary particle is not normally present as
discrete particles
 The processes for manufacturing UF TiO2 are usually similar to
that of pigmentary titanium dioxide ,having adopted many of the
standard unit operations and process equipment from pigment
technology .
The UF and nano product can be sourced from the sulphate ,the
chloride,hydrothermal process ,flame pyrolization or sol-gel method
Process Flow Diagram of manufacture UF TiO2
Crystal
formation
Titanium Dioxide:
How it is made –
UV attenuation grade
Typical
Precipitation
Processes
Titanium
Tetrachloride/
titanyl sulphate
Filtration
Purification
Milling
Coating
Milling
Thermal
Hydrolysis
Water
Cosmetic Oils
Dispersion
UV Attenuation
Dispersion
Grades
UV Attenuation
Powder
Grades
Relative risk assessment for the several industrial
fabrications of nano TiO2
 representative synthesis method was selected based on its potential for scale up
and near-term potential for large-scale production and commercialization .
 A list of input and output materials,and waste streams for each step of
fabrication was developed and entered into a database that included key process
characteristics such as temperarature and pressure.The physical/chemical
properties and quantities of the inventoried materials were used to assess
relative risk based on factors such as
volatibility,carcinogenity,flammability,toxicity,and persistence
The protocol ranks three categories of risk relative to a 100 point scale
(where 100 represents maximum risk) :
incident risk,normal operation risk and latent contamination risk
Product ,manufacturing method
Risk score for
production
process
Nano TiO2 through hydrolysis and
calcination from TiCl4
Nano TiO2 by hydrothermal process
62
Nano TiO2 through hydrolysis and
calcination from titanylsulfat
Refinered petroleum
56
aspirin
58
64
76
Conclusions from risk assessment
 The manufacture of nano TiO2 may present lower risks than of
those of current activities such as petroleum refining, polyolefin
production, and synthetic pharmaceutical production
 Almost as much as constituent substances in a process, differences
in handling operations could have a marked effect on the final risk
scores

Recycling and successful recapture of materials play a key role in
lowering normal operations risk score.
Risk Assessment of exposure to TiO2 nanoparticles
location
hazard
exposure
risk
black session
Minimal of the TiO2
is present as free
particles
zero
zero
up calcination
as above
zero
zero
calcination
The presence of
nanoparticles is higly
unlikely
micronisation
minimal because all
the UF particles are in
aqueous suspension
final powder
product
The hazard is
potentially there but
indications are that
the dust is essentially
aggregated
Minimum exposure minimalize
during normal duties
zero exposure
Exposure levels need
to be established by
the manufacturers
zero
possible
Results for safe procedures for handling nano TiO2
► The main hazards of the production and application of nano
TiO2 are physiological hazards, i.e. by inhalation
► Potential dust exposure occurs only in specific areas of the
plant
► Safe procedure for manufactiring and handling nano TiO2
have defined for each phases of activity
► Wastes of nano TiO2 are not considered hazardous for
disposal into sanitary landfill or industrial waste disposal
landfill.
Conclusions
► The safety of nano TiO2 has been the subject of numerous
experimental and clinical studies and has been fully demostrated.
These studies show no adverse systemic effects with nanoscale
titanium dioxide; no skin penetration detected, no skin irritant or
sensitising potential, no genotoxic potential, no toxic potential by the
oral route, no ecotoxicological potential.
► Low potential to produce tissue inflammation by inhalation.
► Limited human data are limited, quantitative data are available from
rodent studies.To use these data in risk assessment ,a reasonable
approach for extrapolating the rodent data to humans is required.
► Use the best information available to make interim
recommendations on occupational safety and health practises in the
production and use of nano TiO2
► These interim recommendations will be updated as appropriate to
reflect new information
► They will address key components of occupational safety and
health, including monitoring, engineering controls, personal protective
equipment, occupational exposure limits, and administrative controls .
► Additional are required to make a better assessment (for example
NIOSH plans to study airborne exposures to fine and ultra-fine TiO2
along with workplace procedures and end useres in comparison with
unexposed workers ;last year European Commission requested of
additional information for nano TiO2 in cosmetics.)
► TDMA members take all possible precautions against all potential
work place exposures and support the continuous improvement of
procedures and processes to minimalize any potential exposure
NIOSH= National Institute for Occupational Safety and Health,USA
Thank you for your
attention
antonin.mlcoch@precheza.cz
Author acknowledge partial support for this work from Ministry of Industry
of the Czech republic within the framework of state programme TANDEM