# DuPont Chemicals & 

# Fluoroproducts [ May 31,2013 U.S. Environmental Protection Agency Office ofAir 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 ofthe Vertrel® Specialty Fluids Bulletin that we mentioned during the meeting
. Please contact me ifyou have any questions about this submission or need further clarification. Sincerely, [ ] 

## V

ia Federal Express

Ch est nut Run Plaza 702/1276
- E, Wilmi ngton, 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 ofproprietary azeotropes, which are also listed. 

## Applications Vertrel® 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 ofelec

tronic components.

Table 1 Physical and Chemical Properties of Vertrel® Products XMS MCA Property• XF SMT Plus MCA Plus XP XM XE MolecularWeight 252 128 125 156 1 36 226 178 212 Boiling Point, oc 55 37 38 39 38 52 48 52 (oF) (130) (99) (100) (102) (100) (126) (11 8) (126) Surface Tension, dyn/cm 14.1 1 5.5 14

. 9 15.2 1 6.1 1 5

. 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 , o c --80 <-50 <- 50 <-50 <-50 <--80 <--80 <--80 ( oF) (
- 112) (<-58) (<
- 58) (<
- 58) (<-58) (<
- 112) (<-112) (<-112) Flash Point-C losed Cup, b oc (°F) None None None None None None None None Flash Point-Open Cup,c o c 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 Co mponent 

### No Yes Yes Yes Yes Yes Yes Yes • At 25°C (77°F) exce pt wh e r e indicated b Pensky-Martens Closed Cup Tester (ASTM 093)

c Tag Open Cup Tester (ASTM 013 1 0)

### Because ofits nonflammability, most aerosol applications using Vertrel® products are likely to use a nonflammable propellant, i.e., Dymel® 134a
. Vertrel® XF has excellent chemica l 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. Vertrel® 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 ofthe complete formulation (solvent, active ingredients, and propellants) must be evaluated with respect to com pa tibility 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 of400 ppm. Refer to the Mate

rial Safety Data Sheets (MSDS) for additional details
. 

## Guideline for Use Air monitoring data conducted by DuPont using a mixture ofVertrel® XF and D ymel® 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 Vertrel® 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 ofone 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 ofadequate ventilation
. Room purge rate, air recirculation rate , auxiliary ventilation (local exhaust), amount discharged for a given time period, and frequency ofdischarge all need to be considered in defining adequate ventila

tion. Air monitoring of Vertrel® products will confrrm the adequacy ofthe ven tilation 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 Vertrel® 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 ofspray that ricochets back toward the person performing the spra ying
. 

## Controlling the Discharge Rate The discharge rate (spray rate) is controlled by the size ofthe 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 chan ges can be affected by manipulating the second smallest orifice
. The vapor pressur e ofthe formulation as well as the nature of any co-solvent, ifpresent, will also influence the discharge rate .

## Flammability Because the primary use ofVertrel® XF will be as a nonflammable carrier, the propellant ofchoice is Dymel® 134a, which is also nonflammable. However, for some applications (e.g., electronic cleaning) the addition ofother 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 ofDOT. However, these products may have vapor flammability limits in air. Uimits offlamma

bilityprovide 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 exten
sion/flashback testing was performed to determine the minimum amount ofVertrel® XF required to obta in 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 M ethanol 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 pe rformed us i ng

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 ofvarious mixtures ofVertrel®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 B l ends


## 200 180 160 .2l 

## 140 1/) 

### 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 ( 1 30 ' F)

# ---~~-----

# --**~-~----**

20 30**10~/ /**  

# --

40 15?-// 142 //

## 12~_____ .,---



# --

50 

## 60 70 Dyme l® 134a, wt% 196**18~ -----**  

### 1 69
_____ _

72 71 

### 66,_

__ _ 

### ---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 Internat ional 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 61-2-923-6 165 

## (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

-519-3 006 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 setforth herein is basedondatabelievedtoberelia ble, butthe DuPontCompany makesn o warranties expressorimpliedas to its accuracy and assumesno liability aris ing out ofits u sc by others
. Thi s publication is not to be taken as a license to operate under, orrecommendation to infringe, any patent.

(8/00) 2494446 Printed in U
.S
.A. [Repl aces: H

-70016-2] Reorde r 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 20004-3 302 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 ofthat. Abstracts for the cited references are also listed be low. There were no fluoride- related adverse effects identified in the PMN substance ( ) go -day inhalat ion 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 decalcifica tion 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 ofthe commonly employed histology laboratory techniques for softening ofboney tissues involve acid decalcification. This technique was used in the two go -day studies to decalcify b one and teeth. In these studies, there was histologic evidence that in some ofthe 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 ofboney structures to the acid decalcification procedure used in this study, as fluoride (an apparent metabolite ofthe 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 ofbone 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 bythe 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 ofbone, teeth, or other tissues to fluoride. The toxicological significance ofthis exposure was assessed based on the presence or absence of clinical and/or pathological findings typically associated with fluoride toxicity. The absence ofeffects on osteoblasts, as well as the absence of other effects (such as osteosclerosis oflong bones) known to occur following exposure to toxic levels offluoride, was noted only because these are important weights of evidence in assessing the adversity, or lack thereof, offluoride exposure . This is not to imply that the absence of any one known adverse effect offluorosis, 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 ofteeth or osteosclerosis (Eisenbrandt, and Nitschke, 1989; NTP, 1990) were present. Rather, the conclusion ofnon-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 ofteeth) or morphological (damage to bone or tooth structure or degeneration ofbone/teeth fo rming cells) changes suggestive ofinjury or loss offunction ofthese tissues. In summary, the diagnosis of incomplete decalcification refers to a tissue processing phenomenon that indicates that metabolism ofthe 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 ofpotential fluoride exposure to teeth and bone was assessed based upon the presence or absence of clinica l 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 wi fu 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 Nit schke KD (1989)
. Inhalation toxicity of sulfuryl fluoride in rats and rabbits. Fund Appl Toxicol, 

### 12:540

- 557. ACCE SS I O N NUMB ER: DOCUM ENT NUMBER: ORIGINAL REFEREN C

E N O .: TIT LE : A

U

TH OR ( S ): CORPORATE SOU RCE : SOURC E : 1 9 89:226877 CAPLU S 110:2 26877 1 1 0: 3751 1 a , 37514a Inha l at i on tox i c i ty of s ul furyl f luo ride in**~ts** an 1 d rabbi ts El se nb ran d t , D
. L .; Ni tsc hke , K
. D
. M

a mm. Env ir o n. Toxico l. Res
. La b
. , Dow Chern
. Co ., Midl a n d , MI, 48674 , US A Funda m e ntal and App li e d Tox i cology (198 9 ), 1 2 ( 3 ), 

### Page 2

### Contains TSCA Confidential Business Information

540-57 CODEN: FAATD F ; ISSN: 0272-0590 DOCUMENT TYPE: Journal LANGUAGE: En glish AB The inhalation toxicity of th e structural fu migant S02F 2 was evaluated in rats and rabbi ts. Exposures for a preliminary 2-wk s tudy were 6 h / day, 5 days/wk, to 0, 1 00, 300, or 6 00 ppm S02F2. Nine of t en rats at 600 ppm died or were moribund between the second and sixth exposures. Ex t ensive kidn ey lesions were present in all rats exp os ed t o 600 ppm, whereas only minimal re nal ch anges were noted in ra t s a t 300 ppm . Upper and lowe r respir a tory t issues were in f lammed in the s i n g le ra t t h a t surv ived t he 2-wk e xpo s ur e t o 600 ppm. Rabbi t s e xpos e d to 6 00 p pm S02 F2 w e re hyperac t i v e and one animal had a convul sion. Expos ure to 300 or 6 0 0 ppm for 2 wk resulted i n vacuolation and/or malacia in th e cerebrum of all rabbit s and most of these r k bbits a lso had moderate inflammati on of nasal t issues; a fe w rabb its at 600 ppm had inflammati on o f the trac h ea or bronchi. A subse quent 13- wk study eva lua ted rats and rabbits expo sed to 0, 3 0 , 10 0, or 300 ppm S02Fr (337 ppm TW A for rab bit s). Rabbi t s initially w

e re exp ose d to a high con ce ntr at ion of 6 00 p pm ; howe v e r, co n v uls i ons were n oted i n t wo a n i m a l s a f t er nin e e k posu re s a nd t h e conce n t r atio n subse quent l y w as r e du ce d t o 3 00 p p m. V ac uol k t i o n an d/or m a l aci a w ere obs erved i n th e cereb r um of all rabbits at t h e highes t concentration; one rabbit exposed to 100 ppm also had cerebral vacuolation. Rabbi ts at t he highest conc entrati on , as well a s one rabbi t exposed t o 1 00 ppm, had in flammation of the nas al t is sues . Rats exposed to 300 ppm S02 F2 fo k 13 wk had mottled incisor teeth , mini m al renal effec ts , pulmon a ry hi k t ioc yto sis, inflamma tio n of nasal t iss u es, and cerebra l vac u olat i o n. A lso , r ats expo se d to 1 0 0 ppm S02F 2 for 13 w k h a d m

o t t l e d teeth. The f l uo ri d e toxic i t y w as s u g g e s t ed b y mottle d tee t h i n ra t s as we ll as e l evatio n

### ~ serum f luoride level s in r ats a n d r a bb i t s exposed to S02F2 for 13 w k
. Although repeated exposure of ra ts and rab bits to 10 0

- 600 ppm S02Fe resulted in tox ici ty o f the k i dne ys (rats only) , brain, and respi ra t o b y s yste m , n o effec t s were detec ted in an i ma ls exp o sed to 30 ppm fo r 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.go v /pubmed/ 1056087 Abstract Thi rteen m a l e ra t s , 7 or 1 0 m o n t h s ol d, were give n 0
. 0 0 5% N aF in t h e diet o r 0. 025 NaF in t h e drinking w a t er f r o periodl s o f 3 t o 2 0 w eeks
. F e mu r / t ibi a bo n e s w ere d eminera l iz ed i n 3. 2 5 % H N

0 3 , t h e p r ocess be ing wat c h e d o n r adi ograp hs
. As s oo n as all r a di opaque m a te ri a l r epre s ent in g mi n e r al iz e d b o n e h ad d isappeare d , demi nera li za ti on was discont inu ed. I n some ins ta nce s the p r ocess was stopped wh ile som e rad iopaque mat eria l was s t il l prese nt . Hematoxyl i n - eosin stained p araffin sec t i o n s from a l l b o nes s h o w ed deep blu e gr anu l e s , flu ori d e gr anu l es . Transm issi o n e l ectro n m icroscop y a nd se l ec t ed a rea diffrac t ion revea l e d t h a t t h e f luo ride g r an ul es co n t ain m ic rocr y stal line Ca F2
. X

- ray d iff r ac t i on of hydrazi n e - d ep ro t ei n at ed, dem in e ra l i z e d fl uor ot i c bo n e s r e v e a l e d t h e pre se n c e of CaF2 a n d a m i n or u nide n t i fi e d compo n e n t . Th e r es ul t s a r e d i s c u ss e d in r e l at i on t o (1) t h e ide n t i t y of t h e f l u o r ide g ran ul e s , and ( 2 ) t h e i r i n co n s is te n t p r ese n c e i n d e m i n eralize d h a r d t i ss u 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 . A

CCES S I O N NUMBER : D

OC UMENT NUMBER : ORI GI N A

L REFERENCE N O
. : TIT L E : 1 98 0 : 14 0 4 8 5 CAPLU S 92 : 1 4 04 8 5

### 92**227 27** **4a** Ca l c i uu 

### 1 fl u o r ide c o n tai n ing gr a nul e s p r odu ced 

### Page3AUTHOR (S) : CORPORATE SOURCE: SOURCE: 

### Contains TSCA Confidential Business Inform ation

in vitro in ra t bones Lindemann, Ge rtrud; Nylen, M arie U. Dep
. Ora l Diagn o sis, R. Dent. Coll. , Copenh age n , Den
. Scandinavian J ou rn a l of De n t a l Re sea r 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 rmaldeh r de con ta in i ng 1 % NaF
. Following w ash in g, radi o g. controlled demineralization wa s performed in 3.25 % HN03. Ligh t mi crosc opy and trans m issio n e l ect r o n**~c roscopy**  r evealed t he prese n ce o f so - called fluor ide granules in bone trabecula, cartilage, cart ilage remnants , bone cel l s, chrondrocyte and in t he bone marrow . Selec t ed area diffrac t ion in dicated t hat the fluoride granules contained CaF2. X-ray diffrac t ion anal
. of nondemi n eralized NaF-fixed bones were neg. for CaF2. T h e resul t s are discussed and rela t ed tb preci pit a t ion artifacts reported i n demineral ized hard tis sues and to similar CaF2-containing granules observ ed in d eminerali z ed bones a n d incisors of ra ts given hig h dos es of NaF i n diet or drinki n g water . 

### National Academy of Sciences (2006). Fluoride in Drinking Water: A Scientific Review ofEPA's Standards . The National Academies Press, Washington DC, pp. 136. See h ttp :// www.actionpa.org / fluor ide /nrc/N RC

- 20 06.pdf or http://www
. n ap . edu/op e 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 D ate: December 22, 2006 

### I I SBN

- 10 : 0309 1 0128X 

### I I SBN

- 13 : 978-0309101288 M

ost people associate f luoride

### th the practice of in t e n t ion a ll y adding fluoride to public drinking wa ter supp li es for t h e preve n t i o n of t ooth decay
. However , fluoride can also ente r pub l ic water sys tem s from na t u ral sources , i n cluding runoff f r om the weathering of f luoride-c ontai n i n g rocks and soils and leaching from soil in to groun dwat er. Fluoride pollut ion [rom v ar io us indus trial e m issions can al so contamina t e water s uppl ie s . In a f ew areas o[ the Un ited S tat es fl uor ide concentrations in wate r are mu ch higher t h an normal ,

### mos**ly** from nat ur a l sour ces . F luoride i s one of the drinking wa ter co n tamin ants**regu~ated** by t h e U
. S
. Envi ronme n ta l Pro tec t io n Ag ency (EPA) becaus e it can occur at t h k se toxic l eve ls. I n 1 9 86, the EPA estab l ished a maximum al l owable conce n t ration [ or f luo r ide in dr i nking wa ter o f 4 mil l igrams per liter, a g uide lin e designed to p ke v e nt the public from be in g expose d to h armful le vels of f lu oride. Fl u oride i n Drinking W ater revie ws research on various hea lth effe cts from e xposure to fluorid e, inc lu b ing studies conducted in th e las t 1 0 year s.


### National Toxicology Program (1990). 

### Toxicology And Carcinogenesis Studies Of Sodiu m Fluoride, U .S. Dept of Health and Human Services , N ational Institutes of Health, Technical Report Series No . 393 . ACCE SS I O N NUMB ER : D

OCUMENT NUMBER: ORIGINAL REFERENCE NO.: TIT LE :
CORPORATE SOURCE : SOU RCE: 1992 : 5337 9 C APLU S 116:533 7 9 116: 9127a, 9130a Toxicology and carci no genesis studie s of sodium fluorid e (CAS Number 768 1- 49

- 4 ) in F344 / N rats a n d B6C3E1 mi ce (drinkin g wat e r studies ) Na t i onal To x i colog y Program , Res earch Triang le Pa r k, NC,

### s~ R

eport _i (1 990 ), NTP -TR

- 3 9 3 , NIH /P UB

- 91

- 2 8 48 ; Orde r N o . PB91

- 1 78 1 37 , 452 pp . A v a i l
. : NT IS From : Gov
. Rep. Annou n ce . In de x (U
. S .) 1991 , 9 1(14), 

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Abs t r. No. 138,159 DOCUMENT TYPE: Report LANGUAGE: Engl i sh AB Groups of 80 F344/N r a t s and B 6C3F(l ) mice of each sex recei v ed 0 or 175 ppm sodium fluoride and groups of 50 ra t s and mic e of each sex received 25 or 1 00 ppm sodium fluoride in deio ni zed drinking wat er ad libi t um fo r up to 103 wk. Unde r the condi t ions of these 2-yr dosed water s tudi es , there was equivocal evide nc e of carci nogen ic activi ty of sodium flu or i de in male F344/N rats, based on the occurrence of a small number of osteosarcomas in d os ed animals. Equivocal e v iden ce i s a category for uncertain findings de f in ed a s studies t hat a re interpreted as sho w ing a marginal increas e of neop lasms t h a t may be r e lat e d to ch emic a l a d mi n istrat ion
. Th e r e was n o evidence of carcinogenic ac t i v i t y i n fema l e F344/N rats receiving sodi um f l uoride at concns. of 25, 1 0 0, or 1 75 ppm (11, 45, or 79 ppm fluoride) in dri nking water for 2 yr. D os ed rats had lesions typic al of fluorosis of the teeth and female rats receiving f luoride had i ncr eased os t eosclerosis of long bones
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