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2-o I- /52084 201-15208A Test Plan for Diallyldimethylammonium Chloride (DADMAC)

DADMAC HPV COMMITTEE

Members of the Consortium: Ciba Specialty Chemicals Corporation. Nalco Chemical Company SNF Inc.

Summary The member companies of the Diallyldimethylammonium Chloride (DADMAC) Panel hereby submit for review and public comment their test plan for DADMAC under the Environmental Program. DADMAC (CAS No. 7398-69-8) is a monomer used in closed systems in the manufacture of water soluble cationic polymers used as coagulants. There is virtually no exposure to monomer in manufacturing or to polymer during use and the level of monomer in polymer is very low. This product has very low acute and chronic toxicity to experimental animals. There have been no reports of any deleterious effects after several decades of use in industry. DADMAC is not toxic to environmental organisms and is readily biodegradable. We conclude that there is sufficient data on this intermediate and that no further testing is needed to safeguard human health. However, some testing is proposed to generate additional environmental data which we consider would be valuable. Protection Agencys (EPA) High Production Volume (HPV) Challenge

Proposed Test Plan 1. Determination of the acute toxicity in Fathead Minnows (Pimephales promelas) 2. Determination of the acute toxicity in Daphnia magna 3. Determination of the inhibition in blue-green algae (Subspicatus capricornutum)

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Identity Diallyldimethylammonium chloride (DADMAC) is a quartenary ammonium compound

which has been has been manufactured in the United States for at least 40 years. It is the reaction product of allylalcohol with dimethylamine. There are currently 3 manufacturing plants for DADMAC monomer in the United States. There is virtually no exposure to monomer during manufacture and emissions to air, water and soil are very low. The product is used almost exclusively as a monomer in the manufacture of cationic, watersoluble polymers which are used in such industries as water-treatment, paper-making and textile printing. Its structure is shown below:

H Jp3
2

ci+J=cH2
3

Diallyldimethylammonium chloride (DADMAC)

Only a small percentage of this monomer enters interstate commerce as most is polymerized on site either as a homopolymer or as a copolymer with acrylamide or other monomers in order to build molecular weight. Best available technology can drive monomer content in polymer down to 1% on an active polymer basis.

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Test Data The test data available on DADMAC is given in the following table:

Environmental

Studies

Safety Test in Blue Gill Sunfish Effect on Soil Organisms Anaerobic Aquatic Metabolism Anaerobic Soil Metabolism Effects of Microbes on Metabolism Environmental Leachability Plant Availability Human Health Studies in Rats (2) (FHSA) Chemistry Studies

Acute Oral Administration Primary Skin Irritation

(FHSA), Corrosivity (DOT), and Acute Eye Irritation Study in Rats (Ames) Test (2)

Segment I Multigeneration Bacterial Reverse Mutation In vitro Mammalian

Cell Gene Mutation Test L5 178Y TK+/- Mouse Lymphoma Chromosome Aberration Test in cultured Human Lymphocytes

Oral (Gavage) Rat Teratology Oral Absorption, Distribution and Excretion Using C 14 Labeled Monomer & Polymer

13 Weeks Oral Toxicity Feeding Study in Rats 13 Weeks Oral Toxicity Feeding Study in Dogs

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TOXICITY

TO AQUATIC

ORGANISMS
on Aquatic Organisms I I I Strain Blue Gill Sunfish I )
I

Tests Conducted

I
I

Study

I
I

Species Fish

Result LC50=56mg/l

I )
I

Acute Aquatic Toxicity (72h)

The LC50 at 72 hours for Bluegill Sunfish (Lepomis macrochirus) is 56 mg/liter (Johnson, 1971). While DADMAC has not been tested in daphnia, other quaternized monomers used for manufacture of cationic polymers, have. The EC50 for daphnia for those substances is greater than 100 mg/liter. ECOSAR structure activity on DADMAC predicts fish, daphnid, and blue-green algae toxicity of 464,28 and 33 mg/L respectively. An LC 50 in another native species, such as Fathead Minnow (Pimephales promelas), as well as test data for crustaceans, e.g., Daphnia magna, and algae e.g., Subspicatus capricornutum, would decrease uncertainty in this area. No further testing for health effects is proposed at this time. Evaluation of the acute toxicity of DADMAC to environmental organisms is consistent with the objectives of the EPA HPV Challenge Program.

ENVIRONMENTAL

FATE
Environmental Fate Studies Result No effect No effect No effect Mobile Low uptake

Study Effect on Soil Organisms Anaerobic Aquatic Metabolism Effects of Microbes on Metabolism Leachability Plant Availability

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ACUTE AND CHRONIC

TOXICITY

Tests Conducted In Viva Study Acute Oral Toxicity Primary Skin Irritation Corrosivity Acute Eye Irritation Segment I Multigeneration Oral (Gavage) Teratology Oral Absorption, Distribution and Excretion 13 Weeks Oral Toxicity Feeding Study 13 Weeks Oral Toxicity Feeding Study Mouse Micronucleus I Species Rat Rabbit Rabbit Rabbit Rat Rat Rat I Strain Sprague-Dawley New Zealand White New Zealand White New Zealand White Sprague-Dawley Sprague-Dawley Not specified I Result LD50 = 3030 mg/kg Not irritating to skin Not corrosive Not irritating to eyes NOAEL = 1.25 mgikg/day NOAEL = 6.0 mgikg/day

Poorly absorbed

Rat

Not specified

Dog Mouse I

Beagle CD1 In Vitro Negative

Tests Conducted Study Ames Test Ames Test Bacteria Bacteria

Salmonella Salmonella

t. t. I

Not mutagenic Not mutagenic Negative Negative

Chromosome Aberration Test in Cultured Human Lymphocytes Mammalian (L5178Y) Cell Gene Mutation Test Mouse Lymphoma

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Acute Toxicity The acute oral rat LD50 for DADMAC is 3030 mgikg (Sterner, 1975). DADMAC is nonirritating to rabbit skin and eyes. Since potential human exposure is very low, no further testing is for acute toxicity is proposed. Mutagenicity DADMAC has been tested and found negative in the Ames test (San, 1991; de Jouffrey, 1996a), mouse lymphoma (L5 178Y) (de Jouffrey, 1996b), and in human lymphocytes for chromosomal aberrations (de Jouffrey, 1996~). DADMAC has also been tested in vivo in the mouse micronucleus assay and found negative (Putnam, 1991). There was no mutagenic response in any of these tests. Based on these tests DADMAC is not considered to be mutagenic. No further testing for mutagenicity is proposed. Repeated Dose Toxicity DADMAC has been tested in subchronic (13-week) feeding studies in rats and dogs. The NOAEL in rats was 50 mg/kg based on decreased body weight gain in the 500 mg/kg group (LOAEL) (Sterner, 1976). The NOAEL in dogs was 200 mg/kg based on decreased body weight gain in the 800 mg/kg group (Tegeris, 1976). No further subchronic toxicity tests are proposed as the NOAEL is 50 mg/kg. In addition, since DADMAC is clearly non-mutagenic, animal tests for carcinogenicity cannot be justified at this time. Reproductive and Developmental Toxicity

Teratology and reproduction studies have been performed on the hompopolymer of DADMAC, polyDADMAC. This product contains systematically a significant residual amount of DADMAC monomer. With current, best-available technology, the lowest level of monomeric DADMAC that can be achieved during manufacture of this polymer is 1% by weight on a an active polymer basis. At the time these studies were conducted, the residual DADMAC in polyDADMAC was much higher, probably in the 3 to 5% range. In the teratology study, there were no effects observed at the highest level of polymer tested, i.e., 600 mg/kg. The animals were exposed to at least 6 mg/kg of DADMAC monomer per day (i.e., 1% of 600 mg/kg/day) (Palmer, 1991). PolyDADMAC was tested

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in a Segment I reproduction study (Adamik, 1979). The highest dose tested was 125 mg/kg. No effects were observed at this dose level. The animals were exposed to at least 1.25 mg/kg of DADMAC monomer per day. With a NOAEL in subchronic studies of 50 mg/kg/day and a NOAEL in the teratology study of 6 mg/kg/day, no further studies are proposed for reproductive or developmental toxicity. Furthermore, in the subchronic studies on rats and dogs, no adverse histological reproductive system of either male or female animals. Conclusion No further testing for health effects is necessary. findings were reported in the

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BACKGROUND Manufacturing

INFORMATION:

MANUFACTURING

& APPLICATIONS

DADMAC has been manufactured commercially for more than 40 years by the reaction of ally1 chloride with dimethyl amine. This is carried out in a closed system since ally1 chloride is irritating. Commercial Application DADMAC is almost exclusively used in the manufacture of homo- and copolymers (the latter mainly with acrylamide). The concentration of residual monomer in these polymers is between 1 and 5% although current, best-available technology results in the majority of products containing around 1%. These polymers have been extensively tested for toxicity and are non-toxic. They are used in the water-treating, textile printing and paper manufacturing industries. Shipping and Distribution Most of the polymers in the US are manufactured at the same site as the monomer is manufactured. Less then 25% of monomer in the US is shipped for polymerization elsewhere. Worker/Consumer Exposure

There is no significant consumer exposure to DADMAC. Worker exposure is very limited as both monomer and polymer manufacture are carried out in closed systems.

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REFERENCES Adamik, E. (1979). Segment I Multigeneration Research Laboratories, Cincinnati, OH. Study in Rats with Cat Floe T. Wil

de Jouffrey, S. (1996a). Bacterial Reverse Mutation Test - Diallyldimethylammonium chloride. Centre International de Toxicologic (CIT), Miserey, France. de Jouffrey, S. (1996b). 1rr vitro Mammalian Cell Gene Mutation Test L5178Y TK+/chloride. Centre International de Mouse Lymphoma - Diallyldimethylammonium Toxicologic (CIT), Miserey, France. de Jouffrey, S. (1996c). In vitro Mammalian Chromosome Aberration Test in Cultured Human Lymphocytes - Dimethyldiallylammonium chloride. Centre International de Toxicologic (CIT), Miserey, France. Easterday, O.D. (1965a) Oral Absorption, Distribution and Metabolism of 14CDiallyldimethylammonium Chloride Monomer and Polymer. Hazleton Laboratories, Falls Church, VA. Easterday, O.D. (1965b) Acute Oral Absorption - Rats , Diallyldimethylammonium Chloride Polymer and Diallyldimethylammonium Chloride Monomer. Hazleton Laboratories, Falls Church, VA. Johnson, C.D. (1971). DMDAAC Corp., Hemdon, VA. - Safety Test in Blue Gill Sunfish. Woodard Research - Oral

Palmer, K. (1991). Poly (dimethyl diallyl ammonium chloride) (PDADMAC) (Gavage) Rat Teratology Study. Toxic01 Laboratories, Ltd., Ledbury, UK. Putnam, D. (1991). Micronucleus Associates, Bethesda, MD Cytogenetic

Assay in Mice. Microbiological and Catfloc T. University and Catfloc T. and Catfloc T. of

Rieck, C.E. (1980a). Anaerobic Soil Metabolism of DMDAAC of Kentucky, Lexington, KY. Rieck, C.E. (1980b). Anaerobic Aquatic Metabolism University of Kentucky, Lexington, KY.

of DMDAAC

Rieck, C.E. (198Oc). Effects of Microbes on the Metabolism of DMDAAC University of Kentucky, Lexington, KY. Rieck, C.E. (1980d). Plant Availability Kentucky, Lexington, KY. of DMDAAC

and Catfloc T. University

Rieck, C.E. (1980e). Effects of Catfloc T and DMDAAC University of Kentucky, Lexington, KY.

on Soil Microorganisms

San, R. (1991). Salmonella/Mammalian - Microsome Plate Incorporation Mutagenicity Assay (AMES TEST). Microbiological Associates, Rockville, MD. Sterner, W. (1975) Acute Oral Toxicity in Rats. International Bioresearch Laboratories, Hanover, Germany. Sterner, W. (1976). 13 Weeks Oral Toxicity Feeding Study with Monomer in Rats. International Bioresearch Laboratories, Hanover, Germany. Tegeris, A. (1976). DADM: Ninety Day Feeding to Dogs. Pharmacopathics Reserach Laboratories, Laurel, MD. Vinegar, M.B. (1978). Primary Skin Irritation (FHSA), Corrosivity (DOT), and Acute Eye Irritation (FHSA) Studies of CC-47 DMDAAC Monomer. Hilltop Laboratories, Miamiville, OH.

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