DuPont Chemicals & Fluoroproducts 

[ 

May 31,2013 

U.S. Environmental Protection Agency 

Office of Air and Radiation 

Stratospheric Protection Division 

Attention: Margaret Sheppard 

1310 L Street NW, 10th Floor (Room 1029) 

Washington, DC 20005 

Dear Ms Sheppard: 

Reference: [ 

DuPont Chemicals & Fluoroproducts 

Chestnut Run Plaza 702 1276-E 

4417 Lancaster Pike 

Wilmington, DE 19805 

USA 

] 

Follow up information from our Meeting on April30, 2013 

This letter contains attachments that include the follow up information from the meeting that we 

had on April30, 2013 at 1:00 PM as reported to the Office of Pollution Prevention and Taxies. 

Also included is a copy of the Vertrel® Specialty Fluids Bulletin that we mentioned during the 

meeting. 

Please contact me if you have any questions about this submission or need further clarification. 

Sincerely, 

[ 

] 

Via Federal Express 

Chestnut Run Plaza 702/1276-E, Wilmington, DE 19805 

E. I. du Pont de Nemours and Company 

] 
Technical Information 

~ 

Vertrel® 

Specialty Fluids 

Use of Vertrel® Products in Aerosols 

Introduction 

Vertrel® XF (HFC-43-1 Omee; 2,3-dihydroperfluoropentane) is a nonflammable solvent with zero ozone 

depletion potential (ODP) that can be used to replace 

CFC-113, 1, I, 1-trichloroethane, hydrochlorofluorocarbons (HCFCs), and perfluorocarbons (PFCs) 

in industrial aerosol formulations. The physical 

and chemical properties ofVertrel® XF, which 

has exempt status as a volatile organic compound 

(VOC), are presented in Table 1. Vertrel® is 

available in a variety of proprietary azeotropes, 

which are also listed. 

Applications 

V ertrel® XF is completely miscible with most esters, 

ketones, ethers, ether-alcohol solutions, and the 

lower alcohols such as methanol, ethanol, and 

isopropanol. The lower hydrocarbons, such as 

hexane and heptane, and trans-1 ,2-dichloroethylene 

( t-DCE) are also soluble. Unlike CFC-113, Vertrel® 

XF has limited solvency for many high molecular 

weight materials such as hydrocarbon oils, silicone 

oils, waxes, and greases; here combinations with 

many readily miscible esters, alcohols, and lower 

hydrocarbons can be used to enhance solubility. 

Because Vertrel® XF has high solubility for Krytox® 

and other fluorocarbon lubricants, it can be used as 

a carrier fluid for aerosol lubricants as well as mold 

release agents. 

Mixtures ofVertrel® XF with either ethanol, 

methanol, isopropanol, acetone, or t-DCE can be 

used in aerosol applications for cleaning of electronic components. 

Table 1 

Physical and Chemical Properties 

of Vertrel® Products 

XMS MCA 

Property• XF SMT Plus MCA Plus XP XM XE 

Molecular Weight 252 128 125 156 136 226 178 212 

Boiling Point, oc 55 37 38 39 38 52 48 52 

(oF) (130) (99) (100) (102) (100) (126) (118) (126) 

Surface Tension, dyn/cm 14.1 15.5 14.9 15.2 16.1 15.1 14.1 14.1 

Liquid Density, glee at 25°C (7JDF) 1.58 1.37 1.34 1.41 1.33 1.53 1.49 1.52 

Freezing Point, oc --80 <-50 <- 50 <-50 <-50 <--80 <--80 <--80 

(oF) (- 112) (<-58) (<- 58) (<- 58) (<-58) (<- 112) (<-112) (<-112) 

Flash Point-Closed Cup,b oc (°F) None None None None None None None None 

Flash Point-Open Cup,c oc rF) None None 20 (68) None None None None None 

Flammability Limits in Air (vol%) None 7-15 6-15 None 6-11 None 9-11 None 

ODP None None None None None None None None 

Viscosity, cPs 0.67 0.47 0.46 0.49 0.49 0.68 0.63 0.73 

VOC Component No Yes Yes Yes Yes Yes Yes Yes 

• At 25°C (77°F) except where indicated 

b Pensky-Martens Closed Cup Tester (ASTM 093) 

c Tag Open Cup Tester (ASTM 01310) 
Because of its nonflammability, most aerosol 

applications using Vertrel® products are likely to 

use a nonflammable propellant, i.e., Dymel® 134a. 

Vertrel® XF has excellent chemical stability. 

However, it is not compatible with strong bases. 

Thus, Vertrel® XF should not be used in aerosol 

formulations with a pH above 10. 

Compatibility with Plastics and 

Elastomers 

Vertrel® XF is compatible with a wide variety of 

plastics, including polyethylene, polypropylene, 

nylon, polyester, and Teflon®. However, it is not 

compatible with acrylics. 

V ertrel® XF is also compatible with many elastomers, including natural rubber, butyl rubber, 

and neoprene. However, some swelling without 

extraction was observed with fluoroelastomers, 

e.g., Viton® and Kalrez®. 

As with any aerosol formulation, the compatibility 

of the complete formulation (solvent, active 

ingredients, and propellants) must be evaluated 

with respect to compatibility with valve gaskets, 

mounting cup gaskets, and dip tubes. 

Toxicity 

Vertrel® XF has low toxicity. The compound is a 

slight skin and eye irritant and has low inhalatioh 

toxicity. Based on its studies, DuPont has established an Acceptable Exposure Limit (AEL) of200 

ppm (8- and 12-hr time weighted average [TWA]) 

and a ceiling limit of 400 ppm. Refer to the Material Safety Data Sheets (MSDS) for additional 

details. 

Guideline for Use 

Air monitoring data conducted by DuPont using 

a mixture of V ertrel® XF and Dymel® 134a has 

shown that the AEL and ceiling limit requirements 

can be met provided the total discharge ofVertrel® 

XF is less than 30.0 g (1.06 oz) during a continuous 

10-sec spray. Thus, for aerosols using V ertrel® XF, 

follow the guideline below: 

"Formulation and componentry shall be 

designed so as to limit the amount of 

Vertrel® XF discharged into the air in a 

1 O-see continuous spray to 30.0 g." 

This guideline assumes that the aerosol will be 

used with adequate ventilation and that the time 

between sprays is sufficient to avoid accumulation 

ofVertrel® XF. Air monitoring has shown that the 

accumulation ofVertrel® XF is dependent on the 

quantity discharged per spray. 

For example, for a 60/40 wt% Vertrel®XF/Dymel® 

134a mixture, a total of about ten 1 O-see sprays 

at a discharge rate of 1.6 glsec (0.06 oz/sec) can 

be performed every 2- 3 min before significant 

(100 ppm) accumulation ofVertrel® XF occurs. 

Using the same aerosol mixture at a discharge rate 

of 5.0 glsec (0.18 oz/sec) and spraying for 10 sec 

every 4 min, a significant (150 ppm) accumulation 

of Vertrel® XF starts to occur after about five 

sprayings. It is obvious that the accumulation of 

Vertrel® XF will be dependent on the ventilation. 

The accumulation ofVertrel® XF presented above 

was based on a room purge rate of one room volume 

every 13 min with good air recirculation that 

resulted in good mixing. 

Adequate ventilation needs to be used to control 

the concentration ofVertrel® XF in the air with 

respect to both the ceiling limit ( 400 ppm) and 

AEL (200 ppm [8- and 12-hr TWA]). The MSDS 

should include label warnings on ventilation and 

misuse, and label warnings should also include 

warnings regarding the use of adequate ventilation. 

Room purge rate, air recirculation rate, auxiliary 

ventilation (local exhaust), amount discharged for 

a given time period, and frequency of discharge all 

need to be considered in defining adequate ventilation. Air monitoring of Vertrel® products will 

confrrm the adequacy of the ventilation and is, 

therefore, recommended. 

Based on this guideline, aerosol formulations 

containing Vertrel® products must be limited to 

the industrial market rather than consumer or retail 

markets. In using V ertrel® products in aerosols, 

care needs to be exercised and statements should 

be included in the MSDS warning against spraying 

longer than 10 sec, not to spray toward other people, 

and to minimize the amount of spray that ricochets 

back toward the person performing the spraying. 

Controlling the Discharge Rate 

The discharge rate (spray rate) is controlled by the 

size of the various orifices in the valve mechanism. 

Generally, the smallest orifice, be it the stem 

diameter or the actuator orifice, dictates the flow 

rate. However, smaller changes can be affected by 

manipulating the second smallest orifice. The vapor 

pressure of the formulation as well as the nature of 

any co-solvent, if present, will also influence the 

discharge rate. 
Flammability 

Because the primary use ofVertrel® XF will be as 

a nonflammable carrier, the propellant of choice 

is Dymel® 134a, which is also nonflammable. 

However, for some applications (e.g., electronic 

cleaning) the addition of other solvents that are 

flammable may be desirable to increase the cleaning 

efficacy. Such solvents include methanol, ethanol, 

isopropanol, acetone, and t-DCE. Vertrel®blends, 

as indicated in Table 1, exhibit no closed cup flash 

point and are not classified as flammable liquids by 

NFP A of DOT. However, these products may have 

vapor flammability limits in air. Uimits of flammability provide the user with additional information 

that may be used as elements of a fire risk assessment, and to determine guidelines for the safe 

handling of volatile chemicals. When formulating 

these blends in aerosol products, flammability 

properties should be established by flame extension 

and flashback testing. 

To investigate flammability further, flame extension/flashback testing was performed to determine 

the minimum amount ofVertrel® XF required to 

obtain zero flame extension and flashback for the 

binary mixtures using 20 wt% Dymel® 134a 

(Table 2). 

Table 2 

Effect of Vertrel® XF on Flame Extension 

and Flashback 

Solvent 

t-DCE 

Isopropanol 

Ethanol 

Methanol 

Acetone 

Minimum Concentration, wt%, 

of Vertrel® XF Required for 

Zero Flame Extension and 

Zero Flashback* Using 

20 wt% Dymel® 134a 

0 

68 

68 

68 

72 

* Flame extension/flashback testing performed using 

0.05-cm (0.018-in) stem and 0.06-cm (0.025-in) actuator. 

Vapor Pressure of Vertrel® XF 

and Dymel® 134a Mixtures 

Vapor pressures of various mixtures of Vertrel® XF 

and Dymel® 134a are given in Figure 1 at 21 °C and 

54°C (70°F and 130°F). 

Figure 1. Vapor Pressure at 21oc and 54°C (70°F and 130°F) of Dymel® 134a/Vertrel® XF Blends 

200 

180 

160 

.2l 

1/) 140 

c.. 

ai 

... 120 ::I 

1/) 

1/) 100 CD 

... 

a.. 

... 80 0 

c.. 

~ 60 

40 

20 

0 

~,;1,"'/ 

0 10 

21 ' C (70' F) 

54' C (130' F) 

---~~-----

-- ~-~----

20 30 

10~/ / 

--

40 

15?-// 

142 // 

12~ _____ .,---

--

50 60 70 

Dymel® 134a, wt% 

196 

18~-----

169 _____ _ 

72 66,_ __71 _ ---4 

80 90 100 
For Further Information: 

DuPont Fluorochemicals 

Customer Service Center 

Chestnut Run Plaza 

Wilmington, DE 19880-0702 

Europe, Africa, 

Middle East 

DuPont de Nemours 

International S.A. 

2 Chemin du Pavilion 

P.O. Box 50 

CH-1218 Le Grand-Saconnex 

Geneva, Switzerland 

41-22-717-5111 

Canada 

DuPont Canada, Inc. 

P.O. Box 2200, Streetsville 

Mississauga, Ontario 

Canada 

L5M 2H3 

(905) 821 -5953 

Mexico 

DuPont, S.A. de C.V. 

Romero 206 

Col. Chapultepec Morales 

C.P. 11570 Mexico, D.F. 

52-5-722-1000 

South America 

DuPont do Brasil S.A. 

Alameda Itapecuru, 506 

Alphaville 06454-080 Barueri 

Sao Paulo, Brazil 

55-11-7266-8263 

Pacific 

DuPont Australia 

P.O. Box 930 

North Sydney, NSW 

Australia 2060 

61-2-923-6165 

(800) 441-9281 

To Order: (800) 937-2494 

Visit our Web site at www.dupont.com/vertrel 

Japan 

DuPont-Mitsui 

Fluorochemicals 

Co., Ltd. 

Chiyoda Honsha Bldg. 

5-18 Sarugaku-cho 1-Chome 

Chiyoda-Ku, Tokyo 101, 

Japan 

(03) 5281 -5805 

Asia 

DuPont Taiwan 

P.O. Box 81-777 

Taipei, Taiwan 

886-2-514-4400 

DuPont Asia Pacific, Ltd. 

P.O. Box TST 98851 

Tsim Sha Tsui 

Kowloon, Hong Kong 

852-734-5345 

DuPont Thailand 

G.P.O. Box 2398 

Bangkok 10500, Thailand 

66-2-236-0026 

DuPont Far East, Inc. 

8/F Solid Bank Bldg. 

777 Paseo de Roxas 

Makati 1226 Philippines 

63-2-818-9911 

DuPont Far East Inc. 

P.O. Box 7882 

40702 Shah Alam, Malaysia 

60-3-519-3006 

DuPont Korea Ltd. 

C.P.O. Box 5972 

Seoul, Korea 

82-2-721-5114 

DuPont Singapore Pte. Ltd. 

1 Maritime Square #07 01 

World Trade Centre 

Singapore 0409 

65-273-2244 

I The information set forth herein is based on data believed to be reliable, butthe DuPont Company makes no warranties express or implied as to its accuracy and assumes no liability 

arising out of its usc by others. This publication is not to be taken as a license to operate under, or recommendation to infringe, any patent. 

(8/00) 2494446 Printed in U.S.A. 

[Replaces: H-70016-2] 

Reorder No.: H-70016-3 

~ 

Vertrel® 

Only by DuPont 
May3o, 2013 

U.S. Environmental Protection Agency 

Office of Pollution Prevention and Toxics 

Confidential Business Information Center (CBIC) - TS7407M 

Attention: Audrey Binder 

EPA East Building, Room 6428 

1201 Constitution Avenue, NW 

Washington, DC 20004-3302 

Dear Ms. Binder: 

Reference: PMN P-11-0549 

Submission Report Number -

Follow-up Information from our Meeting on 

April 30, 2013 at 1:00 PM 

As requested, please find an explanation regarding the decalcification described in the inhalation studies 

conducted on the PMN substance 

. The Agency was more specifically interested in the lack of impact to the osteoblasts 

and the significance of that. Abstracts for the cited references are also listed below. 

There were no fluoride- related adverse effects identified in the PMN substance ( ) go-day 

inhalation studies (see 17453-785 and 17453-785-1), including no evidence of 

osteosclerosis or any other change in bone associated with skeletal fluorosis (NTP, 1ggo). The incomplete 

decalcification referred to in the study reports does not represent an in vivo effect of decalcification on the 

bone or tooth, but rather, was likely a histological processing artifact. Hard tissues such as bones and 

teeth must be softened (i.e., decalcified or demineralized) before they can be trimmed and sectioned in 

preparation of routine hematoxylin- and eosin-stained slides for microscopic examination. Most of the 

commonly employed histology laboratory techniques for softening ofboney tissues involve acid 

decalcification. This technique was used in the two go-day studies to decalcify bone and teeth. In these 

studies, there was histologic evidence that in some of the l>MN substance ( ) exposed 
Contains TSCA Confidential Business Information 

groups, the laboratory process of acid decalcification in some bone and the incisor teeth was not complete. 

This observation was noted by the diagnosis of "incomplete decalcification". 

As noted and referenced in the study reports, the observation that the bone was not completely decalcified 

by the decalcification procedure may be related to resistance of boney structures to the acid decalcification 

procedure used in this study, as fluoride (an apparent metabolite of the PMN substance ( 

) can impart resistance to acid breakdown in mineralized tissue such as bone and tooth enamel. 

Somewhat similar observations (described as deep blue-staining granular material) in fluoride-exposed 

animals have been shown to represent post mortem artifacts (Lindemann, 1975) that can be reproduced in 

tissues of animals unexposed to fluoride by immersion fixation of bone and teeth in fixative containing 

sodium fluoride (Lindemann and Nylen, 1979). Based on these considerations, it is likely that some 

pathologists may not even note this observation since it is, in some respects, a processing artifact rather 

than a lesion. It was reported by the pathologists in these studies because it provides evidence- in much 

the same manner as the urinary fluoridk analysis- that the parent compound is metabolized to a free 

fluoride, and that exposure to the parent material is associated with potential exposure of bone, teeth, or 

other tissues to fluoride. The toxicological significance of this exposure was assessed based on the 

presence or absence of clinical and/or pathological findings typically associated with fluoride toxicity. 

The absence of effects on osteoblasts, as well as the absence of other effects (such as osteosclerosis oflong 

bones) known to occur following exposure to toxic levels of fluoride, was noted only because these are 

important weights of evidence in assessing the adversity, or lack thereof, of fluoride exposure. This is not 

to imply that the absence of any one known adverse effect of fluorosis, such as attenuation or proliferation 

of osteoblasts (NAS, 2006), would indicate a non-adverse exposure level if other adverse effects, such as 

clinically observable mottling of teeth or osteosclerosis (Eisenbrandt, and Nitschke, 1989; NTP, 1990) 

were present. Rather, the conclusion of non-adversity for the teeth and bone observations noted in the 

90-day studies with the PMN substance ( ) was based upon the absence of any clinical 

(abnormal growth or mottling of teeth) or morphological (damage to bone or tooth structure or 

degeneration of bone/teeth forming cells) changes suggestive of injury or loss of function of these tissues. 

In summary, the diagnosis of incomplete decalcification refers to a tissue processing phenomenon that 

indicates that metabolism of the parent material, PMN substance ( ), includes production 

of a free fluoride. Thus, "incomplete decalcification" in these studies is not a lesion per se but evidence of 

fluoride exposure. The significance of potential fluoride exposure to teeth and bone was assessed based 

upon the presence or absence of clinical and/ or microscopic changes suggestive of injury or loss of 

function in these tissues. Based on the absence of such changes, the microscopic findings noted in the 

teeth and bone in the 90-day studies wifu the PMN substance ( ) were considered 

indicative of exposure to a fluoride metabolite of the parent material, but were not considered to be 

adverse. 

References: 

Eisenbrandt DL and Nitschke KD (1989). Inhalation toxicity of sulfuryl fluoride in rats and rabbits. Fund 

Appl Toxicol, 12:540- 557. 

ACCESS I ON NUMBER: 

DOCUMENT NUMBER: 

ORIGINAL REFERENCE NO.: 

TITLE : 

AUTHOR (S ): 

CORPORATE SOURCE : 

SOURCE : 

1 989:226877 CAPLUS 

110:226877 

1 10: 3751 1a , 37514a 

Inhal ati on toxi c i ty of s ulfuryl f luoride in 

~ts an1d rabbits 

Elsenb rand t , D. L.; Nitschke , K. D. 

Mamm. Environ. Toxicol. Res . La b . , Dow Chern . Co ., 

Midla nd , MI, 48674 , USA 

Fundame ntal and Applie d Toxi cology (198 9 ), 12 (3 ), 

Page 2 
Contains TSCA Confidential Business Information 

540-57 

CODEN: FAATDF; ISSN: 0272-0590 

DOCUMENT TYPE: Journal 

LANGUAGE: English 

AB The inhalation toxicity of the structural fumigant S02F2 was evaluated in 

rats and rabbits. Exposures for a preliminary 2-wk s tudy were 6 h / day, 5 

days/wk, to 0, 1 00, 300, or 600 ppm S02F2. Nine of t en rats at 600 ppm 

died or were moribund between the second and sixth exposures. Ex t ensive 

kidney lesions were present in all rats exposed t o 600 ppm, whereas only 

minimal renal changes were noted in rat s a t 300 ppm. Upper and lower 

respira tory t issues were inf lammed in the s i ng le rat t ha t surv ived t he 

2-wk e xpos ure t o 600 ppm. Rabbit s e xpos e d to 600 ppm S02 F2 we re 

hyperact i v e and one animal had a convulsion. Exposure to 300 or 600 ppm 

for 2 wk resulted i n vacuolation and/or malacia in the cerebrum of all 

rabbits and most of these r kbbits a lso had moderate inflammation of nasal 

t issues; a few rabbits at 600 ppm had inflammation o f the trachea or 

bronchi. A subsequent 13-wk study evaluated rats and rabbits exposed to 

0, 3 0 , 100, or 300 ppm S02Fr (337 ppm TWA for rabbits). Rabbit s initially 

we re exposed to a high concentration of 600 p pm; howev e r, conv ulsi ons were noted 

i n t wo a ni ma l s a f t er nine e kposures a nd t he concen t r ation subsequentl y was 

r e duced t o 300 p pm. Vacuolk t i o n and/or ma l acia were observed i n the cereb r um 

of all rabbits at t he highest concentration; one rabbit exposed to 100 ppm also 

had cerebral vacuolation. Rabbits at t he highest concentration , as well a s one 

rabbit exposed t o 1 00 ppm, had inflammation of the nasal t issues . Rats 

exposed to 300 ppm S02F2 fok 13 wk had mottled incisor teeth, minimal 

renal effects, pulmona ry hikt iocytosis, inflammation of nasal t issues, and 

cerebra l vacu olat i on. Also, r ats exposed to 1 00 ppm S02F2 for 13 wk ha d 

mo t t l e d teeth. The f l uoride toxici t y was s ug g e s t ed b y mottled teet h i n 

rat s as well as e l evation ~ serum f luoride levels in r ats a nd r abbi t s 

exposed to S02F2 for 13 wk . Although repeated exposure of rats and 

rab bits to 100 - 600 ppm S02Fe resulted in toxicity o f the ki dneys (rats 

only) , brain, and respirat o by s ystem, no effect s were detected in ani mals 

expo sed to 30 ppm for 13 wk . 

Lindemann G (1975). Calcium fluoride in demineralized bones from rats with experimental chronic 

fluorosis. Scand. J. Dent. Res., 83:75-87. 

See http://www.ncbi.nlm. n ih.gov /pubmed/ 1056087 

Abstract 

Thirteen ma l e rat s , 7 or 1 0 mo n t h s old, were given 0 . 0 05% NaF in t he diet o r 0. 025 NaF 

in t h e drinking wa t er f r o periodls o f 3 t o 2 0 weeks . Femur / t ibia bone s were 

d emineral ized i n 3. 25% HN0 3 , t he p r ocess being watc h e d on r adi ograp hs . As s oon as all 

r a diopaque ma teria l r epres enting mine r alize d b one had d isappeare d , demi nerali zation 

was discontinued. I n some instances the p r ocess was stopped wh ile some radiopaque 

mat erial was s t ill present . Hematoxyli n - eosin stained paraffin sect i on s from a l l bones 

s h owed deep blue granu l e s , fluorid e granul es . Transmission e l ectron microscopy a nd 

sel ect ed a rea diffract ion reveal e d t ha t t he f luoride g r anules con t ain microcrystalline 

CaF2 . X- ray diff r act i on of hydrazine - d eprot einated, demine ral i z e d fluoroti c bon e s 

r e v e a l e d t he presenc e of CaF2 a nd a mi nor u nide n t i fi e d compone n t . The r esult s a r e 

d i s c u sse d in r e l ati on t o (1) t he ide n t i t y of t he f l uo r ide g ranule s , and (2 ) t h e i r 

i ncon s isten t p r esen c e i n d emi neralized h a r d t i ssu e s . 

Lindemann G and Nylen MU (1979). Calcium fluoride containing granules produced in vitro in rat bones. 

Scand. J. Dent. Res., 87:381-389. 

ACCES SI ON NUMBER : 

DOCUMENT NUMBER: 

ORI GINAL REFERENCE NO. : 

TITLE : 

1 98 0 : 14 0 485 CAPLUS 

92 : 1 404 8 5 

92 227 27 4a Ca l c i uu

1 

fl u o r ide c o n tain ing gra nule s p r odu ced 

Page3 
AUTHOR (S) : 

CORPORATE SOURCE: 

SOURCE: 

Contains TSCA Confidential Business Information 

in vitro in rat bones 

Lindemann, Ge rtrud; Nylen, Marie U. 

Dep . Ora l Diagnosis, R. Dent. Coll. , Copenhagen , Den . 

Scandinavian J ourna l of Den t a l Re sear c h (1979), 87(5), 

381-9 

CODEN: SJDRAN; ISSN: 0029-845X 

DOCUMENT TYPE: Journal 

LANGUAGE: English 

AB Femurs and t ibias of normal rats were fixed in 4 g unbuffered solns. of 

glutaraldehyde or fo rmaldehr de containi ng 1% NaF . Following washing, radiog. 

controlled demineralization was performed in 3.25% HN03. Light microscopy 

and transmission e l ectr o n ~c roscopy r evealed t he presen ce o f so- called 

fluoride granules in bone trabecula, cartilage, cart ilage remnants, bone 

cell s, chrondrocyte and in t he bone marrow . Select ed area diffract ion 

indicated t hat the fluoride granules contained CaF2. X-ray diffract ion 

anal . of nondemineralized NaF-fixed bones were neg. for CaF2. The result s 

are discussed and relat ed tb precipita t ion artifacts reported i n demineralized 

hard tissues and to similar CaF2-containing granules observ ed in d eminerali z ed 

bones a nd incisors of rats given high doses of NaF i n diet or drinking 

water . 

National Academy of Sciences (2006). Fluoride in Drinking Water: A Scientific Review of EPA's 

Standards. The National Academies Press, Washington DC, pp. 136. 

See h ttp ://www.actionpa.org/ fluoride /nrc/NRC- 20 06.pdf or 

http://www . nap . edu/ope nbook.php? record id=ll57l&page=l 

Abstract from http://www.arnazon. l orn/Fl:oride-Drinking-Water-ScientificStandards/dp/030910128X 

Book Description 

Publicat ion Date: December 22, 2006 I I SBN- 10 : 03091 0128X I I SBN- 13 : 978-0309101288 

Most people associate f luoride th the practice of int e n t iona lly adding fluoride to 

public drinking water supplies for t h e preven t i on of t ooth decay . However, fluoride 

can also enter publ ic water systems from nat u ral sources, i ncluding runoff f r om the 

weathering of f luoride-contain i ng rocks and soils and leaching from soil into 

groundwater. Fluoride pollution [rom various industrial emissions can also contaminat e 

water s upplies . In a f ew areas o[ the United States fluoride concentrations in water 

are much higher t h an normal , mos ly from nat ura l sources . Fluoride i s one of the 

drinking water con taminants regu~ated by t h e U. S . Environmen tal Protect ion Agency 

(EPA) because it can occur at t h k se toxic l evels. I n 1 986, the EPA establ ished a 

maximum all owable concen t ration [ or f luor ide in dri nking water o f 4 mill igrams per 

liter, a g uide line designed to p ke v e nt the public from being exposed to harmful levels 

of f luoride. Fl uoride i n Drinking Water reviews research on various health effects 

from e xposure to fluoride, inclub ing studies conducted in the last 1 0 years. 

National Toxicology Program (1990). Toxicology And Carcinogenesis Studies Of Sodium Fluoride, U.S. 

Dept of Health and Human Services, National Institutes of Health, Technical Report Series No. 393. 

ACCESSI ON NUMBER : 

DOCUMENT NUMBER: 

ORIGINAL REFERENCE NO.: 

TITLE : 

CORPORATE SOURCE : 

SOURCE: 

1992 : 5337 9 CAPLUS 

116:5337 9 

116: 9127a, 9130a 

Toxicology and carcinogenesis studies of 

sodium fluoride (CAS Number 7681-49- 4 ) in F344 / N rats 

a nd B6C3E1 mice (drinking wat e r studies) 

Nat i onal Tox i cology Program, Research Triang le Par k, 

NC, s~ Report _i (1 990 ), NTP-TR- 3 9 3 , NIH/PUB- 91 - 28 48 ; Orde r No . 

PB91 - 1 78 137 , 452 pp . Av a i l . : NTIS 

From: Gov . Rep. Announce . Index (U. S .) 1991 , 91(14), 

Page4 
Contains TSCA Confidential Business Information 

Abst r. No. 138,159 

DOCUMENT TYPE: Report 

LANGUAGE: Engli sh 

AB Groups of 80 F344/N r a t s and B6C3F(l) mice of each sex receiv ed 0 or 175 

ppm sodium fluoride and groups of 50 rat s and mice of each sex received 25 

or 1 00 ppm sodium fluoride in deionized drinking water ad libit um for up 

to 103 wk. Under the condit ions of these 2-yr dosed water s tudi es, there 

was equivocal evidence of carcinogenic activity of sodium fluori de in male 

F344/N rats, based on the occurrence of a small number of osteosarcomas in 

d osed animals. Equivocal e v idence i s a category for uncertain findings 

de f ined a s studies t hat a re interpreted as showing a marginal increase of 

neop lasms t ha t may be r e late d to chemica l a dmin istration . The r e was n o 

evidence of carcinogenic act i v i t y i n fema l e F344/N rats receiving sodi um 

f l uoride at concns. of 25, 1 00, or 175 ppm (11, 45, or 79 ppm fluoride) in 

drinking water for 2 yr. Dosed rats had lesions typical of fluorosis of 

the teeth and female rats receiving f luoride had i ncreased ost eosclerosis 

of long bones . 

Please contact me if you have any questions about this submission or need further clarification. 

ViaCDX 

cc: Margaret Sheppard (Office of Air and Radiation) via Federal Express 

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