Reference Type: Personal Communication

Author: C.-Y. Chen

Year: 2008

Title: Personal communication. Nano-TiO 2 and fine TiO 2 used in mouse studies Recipient: A. Wang

Short Title: Personal communication. Nano-TiO 2 and fine TiO 2 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. do i: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 potentia l impairment on central nervous system by intranasally instilled TiO2 nanoparticles. Toxic ology.doi:10.1016/j.tox.2008.1009.1014.

--Wang JX; Li YF; Zhou GQ; Li B; Jiao F; Chen CY; G ao YX; Zhao YL; Chai ZF. (2007)
[Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different expos ure 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 admin istration. 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 ppa er 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 re sults 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 mal e mice are strange, so we didnot

use it.

(2) I am wondering whether the vacuoles in the hipp ocampus is functionally important. There was no discussion about brain toxicity in the artic le. Yes, it is a good comment. We asked the pathologist vacuoles in the hippocampus could be the fatty degeneration, which can be recovered. The refore, we did neurological effects.(3) Would it be fair to say that female mice are mo re sensitive to nano-TiO2 than male mice in

this study? It would be better to say a little bit, but, we nee d more evidence.

*4) There are no changes in BUN (5.7 to 6.5 in trea ted and controls ) or Cr (33.3 to 35.7 in treated and controls) in male mice treated with nan o-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 p articles". Could you clarify this for me? Please refer the table. Some changes, but not sign ificantly.

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 a nswer 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 l abelled 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 t hat are accepted for publication recently. One is still proof for correction (Tox L etter), just for your reference. If you are interested, you may get a corrected copy from the w ebsite 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/chenchunyin g.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 To xicity 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 addition al 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 seve ral listed online, but I cannot be certain from which company it was.

Could you provide more information on the character istics 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-T iO2 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 nanopa rticles are anatase. (2) there are not any coating on the surface. (3) I did not do photocatalytic or photostable experim ents. It is hard to say. (4) Yes, the same TiO2 materials for the neurotransmit ters 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 t he 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/chenchunyin g.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 pro viding additional information on TiO2 used in your study entitled Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral admin istration, which was published in Toxicology Letters 168 (2007) 176–185. I would lik e 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 Ch emical 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 2 007 study published in Chinese [Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different expos ure 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 Ti O2 particles1161503376/oral—serum parameters induced by TiO2 pa rticles.docFrom Dr. Chunying Chen Nov 8 2008 EmailData forAcute Toxicity and Biodistribution of Different Sized Titanium Dioxide Particles in Mice after Oral Administration (Toxicology Letter 168(2007) 176-85)Changes of biochemical parameters in the serum of mice induced by TiO2particlesGroupsTBIL(μmol/L)ALT(U/L)AST(U/L)ALT/ASTALP(U/L)UA(μmol/L)Cr(μmol/L)BUN(mmol/L)CK(U/L)Malecontrol(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±0.8 596±18980-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±0.7 594±11625-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±0.73 495±51Fine(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 ±1.1 494±102FemaleControl(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±0.8 508±21925-nm(n=7)0.8±0.2 21.3±2.2*76.0±12.50.28 ±0.03*83.5±16.3150.3±21.437.8±3.26.42±0.65*,+517±14080-nm(n=9)0.7±0.3+16.6±5.2 85.4 ±16.5 0.20 ±0.06 71.1±22.2152.1 ±52.535.5±3.55.48±0.86605±242155-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±4.95.5±0.9522±112From Dr. Chunying Chen Nov 8 2008 Email

Data for Acute Toxicity and Biodistribution of Different Siz ed Titanium Dioxide Particles in Mice after Oral Administration (Toxicology Letter 168(20 07) 176-85)

Table 1: Basic characteristics of TiO 2 particle

Size Mean particle size(nm) Surface are a (m 2 /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