Reference Type: Personal Communication 

Author: C.-Y. Chen 

Year: 2008 

Title: Personal communication. Nano-TiO2 and fine TiO2 used in mouse studies 

Recipient: A. Wang 

Short Title: Personal communication. Nano-TiO2 and fine TiO2 used in mouse studies 

Discussion of material used and results in 

-- Wang J; Chen C; Liu Y; Jiao F; Li W; Lao F; Li Y; Li B; Ge C; Zhou G; Gao Y; Zhao Y; Chai 

Z. (2008) Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the 

anatase and rutile crystal phases. Toxicol Lett. doi:10.1016/j.toxlet.2008.1010.1001. 

-- Wang J; Liu Y; Jiao F; Lao F; Li W; Gu Y; Li Y; Ge C; Zhou G; Li B; Zhao Y; Chai Z; Chen 

C. (2008) Time-dependent translocation and potential impairment on central nervous system 

by intranasally instilled TiO2 nanoparticles. Toxicology.doi:10.1016/j.tox.2008.1009.1014. 

--Wang JX; Li YF; Zhou GQ; Li B; Jiao F; Chen CY; Gao YX; Zhao YL; Chai ZF. (2007) 

[Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic 

neurotransmitters of female mice at different exposure time]. Zhonghua Yu Fang Yi Xue Za 

Zhi. 41:91-95. 

--Wang JX; Zhou GQ; Chen CY; Yu HW; Wang TC; Ma YM; Jia G; Gao YX; Li B; Sun J; Li 

YF; Jiao F; Zhao YL; Chai ZF. (2007) Acute toxicity and biodistribution of different sized 

titanium dioxide particles in mice after oral administration. Toxicol Lett. 168:176-185. 

Email Exchange: 

****************************************************************************** 

From: "chenchy" <chenchy@nanoctr.cn> 11/15/2008 01:54 AM 

To: Amy Wang/RTP/USEPA/US@EPA 

Subject Re: Re: suggestions for Toxicology 2008 ppaer in press 

 

Dear Amy, 

 

You are so careful and would be a right person for compiling data with a great patience. 

Below I would like to answer your questions. 

(1) Do you also have the LDH and alpha-HBDH test results in male mice? They are missing 

from the attached table in your Nov 10 email. 

As I remember, the LDH and alpha-HBDH test from male mice are strange, so we didnot 

use it. 

(2) I am wondering whether the vacuoles in the hippocampus is functionally important. There 

was no discussion about brain toxicity in the article. 

Yes, it is a good comment. We asked the pathologist vacuoles in the hippocampus could be 

the fatty degeneration, which can be recovered. Therefore, we did neurological effects. 
(3) Would it be fair to say that female mice are more sensitive to nano-TiO2 than male mice in 

this study? 

It would be better to say a little bit, but, we need more evidence. 

*4) There are no changes in BUN (5.7 to 6.5 in treated and controls ) or Cr (33.3 to 35.7 in 

treated and controls) in male mice treated with nano-TiO2, compared to controls, in the table. 

However, in the article page 179, section 3.3, "the higher serum BUN and CR levels were found 

in the male mice exposed to the 80 and 25 nm TiO2 particles". Could you clarify this for me? 

Please refer the table. Some changes, but not significantly. 

 

Regards, 

 

CY 

****************************************************************************** 

From: "chunying chen" <chenchy@nanoctr.cn> 

To: Amy Wang/RTP/USEPA/US@EPA 

Date: Saturday, November 08, 2008 05:45PM 

Subject: Re: About your nano and fine TiO2 study (Tox Lett 2007) 

Dear Amy, 

 

Thank you for your message. Below I would like to answer your questions. 

 

(1) TiO2 particles 

Yes, the 155 nm TiO2 may be from one of the several . When 

we bought from a chemical company, the bottle had labelled with 

. 

all three of them are uncoated, the purity >99.9%, pure rutile or anatase. Please 

refer the attachment. 

(2) Male mice results 

If it is not too much trouble, could you share the results of biochemical parameter 

changes in the serum of MALE rats? 

Ok, please refer the attachment. 

I also attached two papers for inhalation studies that are accepted for publication 

recently. One is still proof for correction (Tox Letter), just for your reference. If you are 

interested, you may get a corrected copy from the website after a week. 

Regards, 
chunying 

 

Prof. and Dr. Chunying Chen 

National Center for Nanoscience and Technology 

No. 11, Beiyitiao Zhongguancun, 100080 Beijing 

P. R. China 

Tel:86-10-82545560 

Fax:86-10-62656765 

chenchy@nanoctr.cn 

http://www.china-us-nanobiomed-conf.org/chenchunying.html 

******************************************************************************

Wang.Amy@epamail.epa.gov 

2008-11-09 05:10:20 

chenchy@nanoctr.cn 

chenchy@mail.ihep.ac.cn 

About your nano and fine TiO2 study (Tox Lett 2007)

 

Dear Dr. Chen, 

Greetings. I am writing a case study of nano-TiO2 for US Environmental Protection 

Agency. I came across your study entitled Acute Toxicity and Biodistribution of Different 

Sized Titanium Dioxide Particles in Mice after Oral Administration (Toxicology Letter 

168(2007) 176-85), which is the best study of nano-TiO2 through oral exposure I have 

found. I am hoping you could provide some additional information about your study. 

(1) TiO2 particles 

The 25 nm and 80 nm TiO2 particles seem to be from 

(http://www.dynanotech.com/gsjj/gsjj.htm) . 

I searched the company website, but cannot discern which products were used in your 

study. The 155 nm TiO2 may be from one of the several listed 

online, but I cannot be certain from which company it was. 

Could you provide more information on the characteristics of the nano-TiO2 and fine 

TiO2? For example, are all three of them uncoated? Photocatatlytic or photostable? 

What are their anatase/rutile ratios? 

(2) Male mice results 

If it is not too much trouble, could you share the results of biochemical parameter 

changes in the serum of MALE rats? 

Thank you very much for your help 

Sincerely yours, 

Amy Wang 
************************************* 

Amy Wang, BVM, MS, Ph.D. 

Toxicologist / ORISE Postdoc 

National Center for Environmental Assessment 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 27711 

Email: wang.amy@epa.gov 

Phone: (919) 541-1404 

Fax: (919) 541-0245 

US Postal Mailing Address: 

Mail code: B-243-01 

109 T.W. Alexander Dr. 

RTP, NC 27709 

Other (FedEx, UPS etc) Mailing Address: 

4930 Page Rd 

Durham, NC 27703 

****************************************************************************************************

**************** 

"chenchy" <chenchy@nanoctr.cn> 

08/19/2008 10:00 PM 

To Amy Wang/RTP/USEPA/US@EPA 

Subject Re: TiO2 used in 2007 studies publisehd in Tox Lett and Zhonghua Yu Fang Yi 

XueZa Zhi 

 

Dear Dr. Wang, 

 

Thanks for your email. It is insteresting as Nano-TiO2 has attracted serious concern. I 

would like to answer your question as following: 

 

(1) 80 and 25 nm TiO2 are rutile and 155 nm TiO2 nanoparticles are anatase. 

(2) there are not any coating on the surface. 

(3) I did not do photocatalytic or photostable experiments. It is hard to say. 

(4) Yes, the same TiO2 materials for the neurotransmitters tests. 

 

The attached you will find another two papers about Ti distribution in olfactory bulbs 

after nasal instillation, one in Chinese, for your reference. 

 

In addition, we have submitted two manuscripts on the potential neuro-toxicity of NanoTiO2. 

 
cheers, 

 

chunying 

 

Dr and Prof. Chunying Chen 

National Center for Nanoscience and Technology 

No. 11, Beiyitiao Zhongguancun, 100190 Beijing 

P. R. China 

Tel:86-10-82545560 

Fax:86-10-62656765 

chenchy@nanoctr.cn 

http://www.china-us-nanobiomed-conf.org/chenchunying.html 

2008-08-20 

Wang.Amy@epamail.epa.gov 

2008-08-20 00:47:33 

chenchy@nanoctr.cn 

 

TiO2 used in 2007 studies publisehd in Tox Lett and Zhonghua Yu Fang Yi XueZa Zhi 

 

Dear Dr. Chen, 

Greetings. I am hoping that you would not mind providing additional information on 

TiO2 used in your study entitled Acute toxicity and biodistribution of different sized 

titanium dioxide particles in mice after oral administration, which was published in 

Toxicology Letters 168 (2007) 176–185. I would like to cite and discuss your study in 

the case studies of nano-TiO2 that US Environmental Protecting Agency (EPA) is 

developing. 

(1) What was the anatase/rutile ratio for nano-TiO2 (Hangzhou Dayang Nanotechnology 

Co. Ltd., 80 and 25 nm) and fine TiO2 (Zhonglian Chemical Medicine Co., 155 nm) 

particles? 

(2) Was there any surface coating or doping on any of these three TiO2 particles used? 

(3) Would you say that these TiO2 particles (25 nm, 80 nm, or 155 nm) are 

photocatalytic or photostable? 

(4) Are these TiO2 particles also used in another 2007 study published in Chinese 

[Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic 

neurotransmitters of female mice at different exposure time] published in Zhonghua Yu 

Fang Yi Xue Za Zhi 41(2) 91-5? 
Thank you very much for your help 

Amy 

Amy Wang, BVM, MS, Ph.D. 

Toxicologist 

ORISE Postdoc 

National Center for Environmental Assessment (B-243-01) 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 27711 

Email: wang.amy@epa.gov 

Phone: (919) 541-1404 

Fax: (919) 541-0245 

US Postal Mailing Address: 

Mail code: B-243-01 

109 T.W. Alexander Dr. 

RTP, NC 27709 

Other (FedEx, UPS etc) Mailing Address: 

4930 Page Rd 

Durham, NC 27703 

'File' Attachments: internal-pdf://oral—serum parameters induced by TiO2 particles1161503376/oral—serum parameters induced by TiO2 particles.doc
From Dr. Chunying Chen Nov 8 2008 Email 

Data for Acute Toxicity and Biodistribution of Different Sized Titanium Dioxide Particles in Mice after Oral Administration (Toxicology 

Changes of biochemical parameters in the serum of mice induced by TiO2 particles 

Groups TBIL (μmol/L) ALT (U/L) AST (U/L) ALT /AST ALP (U/L) UA (μmol/L) Cr (μmol/L) BU

(mm

Male 

control 

(n=9) 

1.3±0.8 41.1±10.4 153.3±54.0 0.28±0.06 86.4±16.9 75.2±15.7 35.7±2.9 5.7±

80-nm 

(n=10) 

1.4±0.3 38.3±10.1 123.2±26.2+ 0.31±0.05 94.2±11.0 85.4±20.7 34.2±3.2 6.5±

25-nm 

(n=10) 

1.1±0.3 31.6±9.8 106.2 ±27.7 0.31±0.07 76.6 ±16.5 61.2 ±13.8 34.6±3.4 5.68±

Fine 

(n=9) 

1.4±0.3 32.7±8.0 91.1 ±17.0* 0.36±0.07* 83.0±11.7 71.7 ±25.9 33.3 ±3.4 5.8 ±

Female 

Control 

(n=10) 

0.8±0.3 15.9±4.9 78.2±25.2 0.21 ±0.05 76.3±18.0 137.0±35.7 36.0±7.3 5.1±

25-nm 

(n=7) 

0.8±0.2 21.3±2.2* 76.0±12.5 0.28 ±0.03* 83.5±16.3 150.3±21.4 37.8±3.2 6.42±0

80-nm 

(n=9) 

0.7±0.3+ 16.6±5.2 85.4 ±16.5 0.20 ±0.06 71.1±22.2 152.1 ±52.5 35.5±3.5 5.48±

155-nm 

(n=8) 

1.0±0.2 18.4±3.7 77.9±12.8 0.25 ±0.04 73.9±13.2 134.3±35.1 36.3±4.9 5.5±
From Dr. Chunying Chen Nov 8 2008 Email 

Data for Acute Toxicity and Biodistribution of Different Sized Titanium Dioxide Particles in Mice 

after Oral Administration (Toxicology Letter 168(2007) 176-85)

Table 1: Basic characteristics of TiO2 particle 

Size Mean particle size(nm) Surface area (m2/g) Crystal structure 

 25 nm 21.1 ± 5.1 43.0 rutile 

80 nm 71.4 ± 23.5 22.7 rutile 

 

155 nm 154.9 ± 32.9 10.4 anatase