Page 1 of 2 **UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**

**WASHINGTON, D.C. 20460 OFFICE OF**  **CHEMICAL SAFETY AND POLLUTION PREVENTION** 

**MEMORA NDUM**  **Date :**  September 6 , 2011 **SUBJECT** : CRYOLITE. Response to comments by the Fluoride Action Network (FAN) on the Registration Review for Cry olite **PC Code:** 075101 **DP Barcode:** D391704 **Decision No.:** N/A **Registration No. :**  N/A **Petition No.:** N/A **Re gulatory Action:**  N/A **Risk A**  **ss essment Type:**  N/A **Case No.:** N/A **T XR No.:**  N/A **CAS No.:** 15096
- 52
- 3; 13775
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- 6 **MRID No.: N/A 40 CFR:**  180.145 Ver.Apr. 201 0 **FROM:** Kit Farwell, D.V.M.

Risk Assess ment Branch VII Health Effects Division (7509P) Office of Pesticide Programs **THROUGH** : Michael Metzger, Branch Chief

Risk Assessment Branch VII Health Effects Division (7509P) Office of Pesticide Programs **TO** : Molly

Clay ton, Chemical Review Manager Risk Management and Implementation Branch 3 Pesticide Re

- Evaluation Division (7508P) Office of Pesticide Programs This memo responds to comments by the Fluoride Action Network (FAN) on the Registr ation Review for Cry olite, July 5, 2011. Nearl y all of the comments by FAN relate to fluoride , which is a degradation product of cry olite

. The comments on fluoride will be addressed separatel y ( s ee Docket EPA

- HQ
- OPP
- 2005
- 0174 for comments on fluoride ass essment) . The only comment relating specifically

to human health concerns for cryolite was 3.4.1, and is addressed below.Page 2 of 2

**FAN comment 3.4.1** : OPP should require that testing for adverse effects include cryolite and **all** of its degradation products and complexes. Cryolite degrades to fluoride, aluminum, and sodium in the environment, but according to EPA, the only degradation product of concern is fluoride, and the only effect of concern is severe dental fluorosis. W

hile OPP is requiring that free ion concentrations of Al3+, F

- , and Na+ be used to estimate toxicity, this ignores the effects of complexes formed from these ions. Aluminofluoride complexes are formed spontaneously in water containing fluoride and trace amounts of aluminum. These complexes h ave been found to stimulate various G proteins, and thus may “mimic or potentiate the action of numerous extracellular signals and significantly affect many cellular responses” (Strunecka and Patocka, 1999). OPP should therefore immediately require that toxicity testing of cryolite be extended to include all of its degradation products, including the various aluminofluoride complexes formed under different aquatic conditions. **EPA response** : Aluminum is the third most abundant element in the earth's crust and is a component in food ingredients, food containers, drinking water, and utensils used in food preparation. As a consequence, aluminum is commonly found in foods and most foods that have been tested were found to contain 0.1

– 10 ppm aluminum. A much larger source of oral exposure to aluminum is reportedl y from antacids and buffered analgesics. A 2001 review article reported that "(n) o reports of dietary aluminum toxicity

to healthy

individuals exist in the literature". Because aluminum exposure to p eople is so ubiquitous, the small amount of aluminum in di etary

residues from cry olite is not expected to have an adverse health effect. FAN was specificall y concerned that aluminofluoride complexes would affect G proteins and cellular signaling pathway s. However, cry olite has alread y been evaluated in a number of toxicity studies, including a battery of acute toxicity

studies in different species, subchronic oral toxicity studies in rats and dogs, chronic toxicity in rats and dogs, carcinogenicity in r ats and mice, developmental toxicity in rats, rabbits, and mice, reproductive toxicity in rats, and in vitro mutagenicity

studies. The oral exposure to cry olite in the many toxicity studies with different animal species has allowed evaluation of the toxic ity potential for cry olite and its aluminum and fluoride degradation products and complexes. For the above reasons, the aggregate fluoride risk assessment focused upon dental fluorosis, the most sensitive endpoint f or human health risk assessment, which will be protective of other effects occurring at higher dose. **References** : 1. Aluminum in Foods and the Diet, JC Sherlock. Aluminum in Food and the Environment , editors RC Massey and D Taylor, 1989 2. Safety

Evaluation of Dietary

Aluminum. MG Soni, e t al

. Regulatory Toxicology and Pharmacology

. 2001 Feb;33(1):66

- 79 3. Casarett & Doull's Toxicology, 7th edition

.