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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 

OFFICE OF CHEMICAL SAFETY AND

 POLLUTION PREVENTION

MEMORANDUM

Date: September 6, 2011

SUBJECT: CRYOLITE. Response to comments by the Fluoride Action Network (FAN) 

on the Registration Review for Cryolite

PC Code: 075101 DP Barcode: D391704

Decision No.: N/A Registration No.: N/A

Petition No.: N/A Regulatory Action: N/A

Risk Assessment Type: N/A Case No.: N/A

TXR No.: N/A CAS No.: 15096-52-3; 13775-53-6

MRID No.: N/A 40 CFR: 180.145

 Ver.Apr. 2010

 

FROM: Kit Farwell, D.V.M.

Risk Assessment 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 Clayton, 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 Registration 

Review for Cryolite, July 5, 2011. Nearly all of the comments by FAN relate to fluoride, which 

is a degradation product of cryolite. The comments on fluoride will be addressed separately (see 

Docket EPA-HQ-OPP-2005-0174 for comments on fluoride assessment). The only comment 

relating specifically to human health concerns for cryolite was 3.4.1, and is addressed below. 
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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. While 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 have 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 reportedly 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 people is so ubiquitous, the small amount of 

aluminum in dietary residues from cryolite is not expected to have an adverse health effect. 

FAN was specifically concerned that aluminofluoride complexes would affect G proteins and 

cellular signaling pathways. However, cryolite has already 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 rats and 

mice, developmental toxicity in rats, rabbits, and mice, reproductive toxicity in rats, and in vitro

mutagenicity studies. The oral exposure to cryolite in the many toxicity studies with different 

animal species has allowed evaluation of the toxicity potential for cryolite 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 for 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, et al. 

Regulatory Toxicology and Pharmacology. 2001 Feb;33(1):66-79

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