SRC TR

- 10

- 119

HPV4 CHEMICAL DATA A DEQUACY REVIEW

Quaternary ammonium compounds, benzylbis(hyrdogenated tallow alkyl)methyl, chlorides,

CAS No. 61789

- 73

- 9

Prepared by:

Chris Janson, Justine Von Runnen, and Joan D. Garey

Chemical, Biolo gical and Environmental Center

SRC, Inc.

7502 Round Pond Road

North Syracuse, NY 13212

Contract No. EP

- W

- 09

- 027

Task FG007.0.009.002

Submitted to:

OPPT/RAD/HPVCB (7403M)

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue

Washington, D.C. 20 460

Elizabeth Margosches, Alternate Project Officer

Meena Sonawane, Work Assignment Manager

David Brooks, Alternate Work Assignment Manager

July 9 , 2010HPV4 Chemical Data Adequacy Review

Quaternary am monium compounds, benzylbis(hydr ogenated tallow a lkyl)methyl, chlorides,

CAS No. 61789

- 73

- 9

July 2010

Submitted to:

High Production Volume Chemicals Branch

Risk Assessment Division

Office of Pollution Prevention and Toxics

Environmental Protection Agency

WAM: Meena Sonawane

Alternate WAM: David Brooks

1200 Pennsylvania Avenue, NW

Washington, DC 20460

- 0001

Prepared By:

SRC, Inc.

Environmental Science Center

2451 Crystal Drive, Suite 804

Arlington, VA 22202Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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1 A. PREPARATION OF THE DATA ADEQUACY ASSESSMENTS

A

- 1. Source material us ed for assessment

For this unsponsored chemical, a comprehensive literature search was performed to

identify available toxicity data for the following SIDS endpoints:

Acute toxicity to fish

Acute toxicity to Daphnia

Toxicity to aquatic plants

Acute (ora l, dermal, inhalation) toxicity

Repeated

- dose toxicity

Reproductive toxicity

Developmental toxicity

Gene mutation

Chromosomal aberrations

Studies relevant to non

- SIDS endpoints (e.g., eye and skin irritation; neurotoxicity) conducted

via oral, inhalation, or dermal routes were also identified through literature searching.

The following sources were searched for toxicity data:

PubMed

- B ibliographic database that contains references to journal articles in the life

sciences with a concentration on biomedic ine

T OXNET

- N ational L ibrary of M edicine databases on toxicology, hazardous chemicals,

environmental health, and toxic releases; includes:

**•** TOXLINE with BIOSIS and NTIS ;

**•** Development and Reproductive Toxicology File (DART) ;

**•** Chemical Carcinogenesis Resear ch Information System (CCRIS)

- Carcinogenicity and mutagenicity test results for over 8000

**•** chemicals) ;

**•** Hazardous Substances Data Bank (HSDB)

- Comprehensive, peer

reviewed toxicology data for about 5000 chemicals ;

**•** Genetic Toxicology Data Bank (GENE

- TOX )

- Peer

- reviewed genetic

toxicology test data for over 3000 chemicals.

TSCATS

- U npublished technical reports submitted by industry to the EPA under the

Toxic Substances Control Act]

Registry of toxic effects of chemical substances (RTECs)

Environmenta l Fate Database (EFDB)

ECOTOX

- EPA’s peer

- reviewed ecotoxicology databaseDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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2 EPA’s Integrated Risk Information System (IRIS) website

Agency for Toxic Substances and Disease Registry (ATSDR) website

National Toxicology Program (NTP) website

International Program on Chemical Safety Concise International Chemical Assessment

Documents (IPCS INC HE M or CICADs)

European Chemical Substances Information System (ESIS)

- source of IUCLID Datasets

Any available IUCLID Datasets found through the ESIS website and ro bust summaries

submitted to EPA by former sponsors on the assigned chemicals were retrieved. Original

sources were obtained for any relevant toxicity data found for the assigned chemicals.

While IUCLID D ataset s sometimes contained studies of interest, certain study

descriptions contained insufficient detail to assess adequacy. In these cases, the primary source

of the study, if available and accessible, was obtain ed and review ed.

A

- 2. Evaluating data adequacy

Using standard OECD testing guideline s and professional judgment as guides, available

toxicity studies for the unsponsored chemical were reviewed for adequacy. Summaries were

prepared for all relevant data found, even if little or no study detail was available. Each study

was summarized acco rding to a standard format and assigned a Klimisch reliability code; all

study summaries for the chemical were combined into a single summary document. For studies

already assigned Klimisch codes (e.g., studies summarized in IUCLID datasets), an explanati on

was provided if the reviewer’s assessment of data adequacy differed from the pre

- assigned

Klimisch code. A table summarizing data availability/adequacy for each SIDS endpoint is

included at the end of the summary document.

B. SPECIFIC INFORMATION ON THE AVAILABLE TOXICITY DATA

The available data for each of the SIDS toxicity endpoints are evaluated on the following

pages. Studies for a common endpoint are grouped together in the document and an endpoint

adequacy assessment is provided near the t op of the first page of the summaries for that

endpoint. If the data available for the endpoint is determined to be inadequate, a basis for that

conclusion is supplied.

No data were located for the unsponsored chemical q uaternary am monium compounds,

b enzylbis(hydr ogenated tallow a lkyl)methyl, chlorides ( CAS No. 61789

- 73

- 9 ). However, this

chemical was evaluated as belonging to the Group II Quat Cluster group. The Group II Quat

Cluster group consists of structurally similar quaternary ammonium compound s (“quats”) that

are characterized by having positively charged nitrogen covalently bonded to three alkyl group

substituents and a benzyl substituent. In finished form, these quats are salts with the positivelyDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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3 charged nitrogen (cation) balanced by a nega tively charged molecule (anion). The most common

anion for the quats in this cluster is chloride.

Alkyl dimethyl benzyl ammonium chloride (ADBAC, CAS No. 53516

- 76

- 0) is a member

of the Group II Quat Cluster. Hazard data generated for ADBAC is represe ntative of the hazard

associated with this class of quaternary ammonium compounds. In this data adequacy review

document, d ata on ADBAC was used to represent the hazard of quaternary ammonium

compounds, benzylbis(hydrogenated tallow alkyl)methyl, chloride s

.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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4 B

- 1. TOXICITY TO AQUATIC VERTEBRATES

Summary of endpoint: Adequate

Study 1: Acute toxicity study on ADBAC in bluegill sunfish

Title: Daily Static

- Renewal Acute 96

- Hour Toxicity Test of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) to Bluegill Sunfish

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 30% ai

METHOD

Method/guideline followed: OPPTS 850.1075

GLP: Not stated

Year study performed: Not stated

Test type : Stat ic

- renewal

Species/strain/supplier: Bluegill sunfish ( Lepomis macrochirus )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESUL TS

Nominal concentrations: Not stated

Measured concentrations: Not statedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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5 Element value: LC50 = 0.515 mg/L; NOAEC = 0.456 mg/L (a.i.)

Remarks: Highly toxic

CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

2

REFERENCES

MRID 4194 72

- 01. Pate, H.O. and D.O. McIntyre. 1991. Daily Static

- Renewal Acute 96

- Hour

Toxicity Test of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) to Bluegill Sunfish.

Study No. SC890050. Unpublished data. Conducted by Batelle Columbus Division for ADBAC

Quat Joint Venture/Chemical Specialties Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1].pdf)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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6 Study 2: Acute toxicity of ADBAC to fathead minnow

Title: Static

- Renewal Acute Toxicity of ADBAC to Fathead Minnow ( Pimephales promelas )

The st udy is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/ strain/supplier: Fathead minnow ( Pimephales promelas )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrat ions: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.28 mg/L; NOAEC = Not Determined (a.i.)

Remarks: Highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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7 CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

2

REFERENCES

MRID 437401

- 03. Sword, M.C. and L. Stuerman. 1993. Static

- Renewal Acute Toxicity of

ADBAC to Fathead Minnow ( Pimephales promelas ). Study No. 41237. Unpublished data.

Conducted by ABC Laboratories Inc. for ADBAC Quat Joint Venture/Chemical Specialties

Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1].pdf)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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8 Study 3: Acute static

- renewal toxicity study of ADBAC to fathead minnow

Title: Static

- Renewal Acute Toxicity of ADBAC to Fathead Minnow ( Pimephales promelas ) in

Dilution Water Amended with 20 mg/L Humic Acid

The s tudy is: Adequate Not Adequate

This study was considered inadequate due to deviations from the guideline, including the

addition of 20 mg/L humic acid to dilution water.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: Fathead minnow ( Pimephales promelas )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Deviations from guideline include additions of 20 mg/L humic acid to

dilution water

RESULTS

Nominal concentrations: Not stated

Measured concentrations: No t stated

Element value: LC50 = 1.4 mg/L; NOAEC = 0.99 mg/L (a.i.)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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9 Remarks: Moderately toxic

CONCLUSIONS

Categorized as moderately toxic to fish

RELIABILITY CODE

3

REFERENCES

MRID 437401

- 01 . Sword, M.C. and L. Stuerman. 1993. Static

- Renewal Acu te Toxicity of

ADBAC to Fathead Minnow ( Pimephales promelas ) in Dilution Water Amended with 20 mg/L

Humic Acid. Study No. 41235. Unpublished data. Conducted by ABC Laboratories, Inc. for

ADBAC Quat Joint Venture/Chemical Specialties Manufacturers Associ ation.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1].pdf)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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10 Study 4: Acute static

- renewal toxicity study of ADBAC to fathead minnow in water amended

with humic acid

Title: Static

- Renewal Acute Toxicity of ADBAC to Fathead Minnow ( Pimephales promelas ) in

Dilution Wate r Amended with 10 mg/L Humic Acid

The study is: Adequate Not Adequate

This study was considered inadequate due to deviations from the guideline, including the

addition of 10 mg/L humic acid to dilution water.

TEST SU BSTANCE

Identity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: Fathead minnow ( Pimephales promelas )

Analytical monitori ng: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Guideline deviations include 10 mg/L humic acid added to dilution water

RESULTS

Nominal concentrations: Not state d

Measured concentrations: Not stated

Element value: LC50 = 0.77 mg/L; NOAEC = 0.53 mg/L (a.i.)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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11 Remarks: Highly toxic

CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

3

REFERENCES

MRID 437401

- 02. Sword, M.C. and L. Stuerman. 1 993. Static

- Renewal Acute Toxicity of

ADBAC to Fathead Minnow ( Pimephales promelas ) in Dilution Water Amended with 10 mg/L

Humic Acid. Study No. 41236. Unpublished data. Conducted by ABC Laboratories, Inc. for

ADBAC Quat Joint Venture/Chemical Specialt ies Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1].pdf)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

- 73

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12 Study 5: Acute toxicity study of ADBAC in fathead minnow

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

Based Molluscicide Using Laboratory Tests

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 50% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Flow

- through

Species/strain/supplier: Fathead minnow ( Pimephales promelas )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistica l methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.36 mg/L (a.i.)

Remarks: Highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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13 CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

3

– Missing data

REFERENCES

Dobbs, M.G., D.S. Cherry, J.C. Scott, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Based Molluscicide Using Laboratory

Tests. Published data. Pro ceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organisms Conference, Toronto, Canada.

(EPA

- HQ

- OPP

- 2006

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- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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14 Study 6: Acute toxicity study of ADBAC to rainbow trout

Title: Daily Static

- Renewal Acute 96

- Hour Toxici ty Test of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) to Rainbow Trout

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 30% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: Rainbow trout ( Oncorhynchus mykiss )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical m ethods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.923 mg/L; NOAEC = 0.619 mg/L (a.i.)

Remarks: Highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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15 CONCLUSIONS

Categorized as high ly toxic to fish

RELIABILITY CODE

2

REFERENCES

MRID 419472

- 02. Pate, H.O. and D.O. McIntyre. 1991. Daily Static

- Renewal Acute 96

- Hour

Toxicity Test of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) to Rainbow Trout.

Study No. SC890051. Unpublishe d data. Conducted by Batelle Columbus Division for ADBAC

Quat Joint Venture/Chemical Specialties Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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16 Study 7: Acute toxicity study of ADBAC in rainbow trout

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

Based Molluscicide Using Laboratory Tests

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information.

TEST S UBSTANCE

Identity: ADBAC

Remarks: 50% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Flow

- through

Species/strain/supplier: Rainbow trout ( Oncorhynchus mykiss )

Analytical monitoring : Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 1.01 mg/L (a.i.)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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17 Remarks: Highly/moderately toxic

CONCLUSIONS

Categorized as highly/moderately toxic to fish

RELIABILITY CODE

3

– Data missing

REFERENCES

Dobbs, M.G., D.S. Cherry, J.C. Scott, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Based Molluscicide Using Laboratory

Tests. Published data. Proceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organisms Conference, Toronto, Canada.

(EPA

- HQ

- OPP

- 2006

- 0339

- 002 1[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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18 Study 8: Acute toxicity study of ADBAC in sheepshead minnow

Title: A 96

- Hour Static Renewal Acute Toxicity Test with Alkyl Dimethyl Benzyl Ammonium

Chloride (ADBAC) in the Sheepshead Minno w ( Cyprinodon variegatus )

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: OPPTS 850.10 7 5

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: S heepshead minnow ( Cyprinodon variegatus )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stat ed

Measured concentrations: Not stated

Element value: LC50 = 0.86 mg/L (a.i.); NOAEC = 0.68 mg/L (a.i.)

Remarks: Highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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19 CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

2

REFERENCES

MRID 424795

- 02 . Sved, D.W., J.P. Swiger t, and G.J. Smith. 1992. A 96

- Hour Static Renewal

Acute Toxicity Test with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in the

Sheepshead Minno ( Cyprinodon variegatus ). Project No. 350A

- 102. Unpublished data.

Conducted by Wildlife International Ltd . for ADBAC Quat Joint Venture/Chemical Specialties

Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

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20 Study 9. Acute toxicity study of ADBAC in inland silverslide

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

Based Molluscicide Using Laboratory Tests

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information as well as testing

of a non

- standard species.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 50% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Flow

- through

Species/strain/supplier: Inland silverside ( Menidia beryllina )

Analytical monito ring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC5 0 = 0.31 mg/L (a.i.)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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21 Remarks: Highly toxic

CONCLUSIONS

Categorized as highly toxic to fish

RELIABILITY CODE

3

- Data missing; Non

- guideline species

REFERENCES

Dobbs, M.G., D.S. Cherry, J.C. Scott, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Based Molluscicide Using Laboratory

Tests. Published data. Proceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organisms Conference, Toronto, Canada.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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22 B

- 2. TOXICITY TO AQUATIC INVERTEBRATES

Summary of endpoint: Adequate

Study 1: Acute toxicity study of ADBAC in Daphnia magna

Title: Daily Static

- Renewal Acute 48

- Hour Toxicity Test of Alkyl Dimethyl Ammonium

Chloride (ADBAC) to Daphn ia magna

.

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 30% ai

METHOD

Method/guideline followed: OPPTS 850.1010

GLP: Not stated

Year study performed: Not stated

Test type: St atic

- renewal

Species/strain/supplier: Water flea ( Daphnia magna )

Analytical monitoring: Not stated

Exposure period: 48 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal c oncentrations: Not stated

Measured concentrations: Not statedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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23 Element value: EC50 = 0.0059 mg/L; NOAEC = Not Determined (a.i.)

Remarks: Very highly toxic

CONCLUSIONS

Categorized as very highly toxic to aquatic invertebrates.

RELIABILITY CODE

2

REFERENCES

MRID 419472

- 03 . Pate, H.O. and D.O. McIntyre. 1991. Daily Static

- Renewal Acute 48

- Hour

Toxicity Test of Alkyl Dimethyl Ammonium Chloride (ADBAC) to Daphnia magna . Study No.

SC 89005 2 . Unpublished data. Conducted by Batelle Columbus Divis ion for ADBAC Quat

Joint Venture/Chemical Specialties Manufacturers Association.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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24 Study 2: Acute toxicity study of ADBAC in Daphnia magna

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADB AC)

Based Molluscicide Using Laboratory Tests

The study is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 50% ai

ME THOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Flow

- through

Species/strain/supplier: Water flea ( Daphnia magna )

Analytical monitoring: Not stated

Exposure period: 48 hours

Number of animals/s ex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.02 mg/L (a.i.)

Remarks: Very highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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25 CONCLUSIONS

Categorized as very highly toxic to aquatic invertebrates.

RELIABILITY CODE

3

- Data Missing

REFERENCES

Dobbs, M.G., D.S. Cherry, J.C. Scott, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Base d Molluscicide Using Laboratory

Tests. Published data. Proceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organisms Conference, Toronto, Canada.

(EPA

- HQ

- OPP

- 2006

- 0339

- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

- 73

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26 Study 3. Acute toxicity study of ADBAC in sal twater mysid

Title: A 96

- Hour Static

- Renewal Acute Toxicity Test with Alkyl Dimethyl Benzyl Ammonium

Chloride (ADBAC) in the Saltwater Mysid (Mysidopsis bahia)

The study is: Adequate Not Adequate

TEST SUBSTANCE

Id entity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: OPPTS 850.10 3 5

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: Mysid shrimp ( Mysidopsis bahia )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Not stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.092 mg/L (a. i.); NOAEC = 0.047 mg/L (a.i.)

Remarks: Very highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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27 CONCLUSIONS

Categorized as very highly toxic to aquatic invertebrates.

RELIABILITY CODE

2

REFERENCES

MRID 424795

- 01 . Sved, D.W., J.P. Swigert, and G.J. Smith. 1992. A 96

- Hour Static

- Ren ewal

Acute Toxicity Test with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in the

Saltwater Mysid (Mysidopsis bahia). Project No. 350A

- 101A. Unpublished data. Conducted by

Wildlife International Ltd. for ADBAC Quat Joint Venture/Chemical Specialties Manufacturers

Association.

(EPA

- HQ

- OPP

- 2006

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- 0021[1])Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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28 Study 4: Acute toxicity study of ADBAC in mysid shrimp

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

Based Molluscicide Using Laboratory Tests

The stu dy is: Adequate Not Adequate

This study was considered inadequate due to missing critical study information.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 50% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test type: Flow

- through

Species/strain/supplier: Mysid shrimp ( Mysidopsis bahia )

Analytical monitoring: Not stated

Exposure period: 96 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Guideline deviations included testing conducted at higher temperature.

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.08 mg/L (a.i.)

Remarks: Very highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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29 CON CLUSIONS

Categorized as very highly toxic to aquatic invertebrates.

RELIABILITY CODE

3

- Data missing

REFERENCES

Dobbs, M.G., D.S. Cherry, J.C. Scott, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (A DBAC) Based Molluscicide Using Laboratory

Tests. Published data. Proceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organisms Conference, Toronto, Canada.

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30 Study 5: Acute toxicity study of ADBAC in eastern oyster

Title: A 48

- Hour Static Acute Toxicity Test with Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) in Embryo Larvae of the Eastern Oyster ( Crassostrea virginica )

The study is: Adequate Not Adequ ate

This study was considered inadequate due to the presence of high mortality in control groups.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% ai

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study performed: Not stated

Test t ype: Static

Species/strain/supplier: Eastern oyster ( Crassostrea virginica ) (embryo larvae)

Analytical monitoring: Not stated

Exposure period: 48 hours

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: No ne stated

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LC50 = 0.055 mg/L (a.i.)

Remarks: Very highly toxicDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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31 CONCLUSIONS

Categorized as very highly toxic to aquatic invertebrates.

RELIABILITY CODE

3

- High control mortality

REFERENCES

MRID 424795

- 03. Sved, D.W., J.P. Swigert, and G.J. Smith. 1992. A 48

- Hour Static Acute

Toxicity Test with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in Embryo Larvae of

the Eastern Oyster ( Crassostrea virgini ca ). Unpublished data. Conducted by Wildlife

International Ltd. for ADBAC Quat Joint Venture/Chemical Specialties Manufacturers

Assocation.

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32 B

- 3. TOXICITY TO AQUATIC PLANTS

Summary of endpoint: Adequate

Study 1: Toxi city study of alkyldimethylbenzylammoniumchloride in Dunaliella sp

.

Title: Toxic Effects of Linear Alkylbenzene Sulfonate, Quaternary Alkylammonium Chloride

and their Complexes on Dunaliella sp. and Chlorella pyrenoidosa

The study is: Adequate Not Adequate

This study was considered inadequate due to testing of a non

- standard species.

TEST SUBSTANCE

Identity: Alkyldimethylbenzylammoniumchloride (R = C12

- 14); abbreviated as BM

Remarks: Purity > 97.5%

METHOD

Metho d/guideline followed: Not stated

Test type: Not stated

GLP: Not stated

Year: circa 1995

Species/strain/supplier: Dunaliella sp.

Element Basis: Not stated

Exposure Period: 24 hours

Analytical Monitoring: Not stated

Statistical Methods: Not st ated

Method remarks:

The test chemical was dissolved with water to make a final concentration between 2 and 0.1 mM.

Dunaliella sp. isolated from an Antarctic high salt lake by Watanuki et al. was used to test the

biological effects of surfactacts by d etermining glycerol content of the cells. The precultures of

test algae were incubtated at 20 +/

- 1 C under continuous lightening at 140 μ E/m 2 /s and sterileDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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33 aeration through 0.2

- μ m filter for approximately 7 days. Modified Johnson’s medium was used

in th is study. The algal culture was taken from a preculture in the exponential growth phase.

The initial cell density was about 6 x 10 6 cells/ml, as counted by Microcellcounter F

- 800. The

200

- ml algal culture and the stepwise graded concentration of BM were added to 300

- ml culture

bottles with two replicates of each concentration. These cultures were incubated without shaking

and aeration of 24 h at 20 +/

- 1 C under continuous lightening at 140 μ E/m 2 /s using a controlled

environmental incubator shaker. The number of cells in the control was almost unchanged from

the initial density during the 24

- h incubation. The coefficient of the control cells was 15.1%

The glycerol contents at each concentration level of the test chemicals were measured by H

NMR after 24 h. The dose

- response curves were drawn by plotting the glycerol contents, which

were shown with the percent of untreated control without surfactant in the ordinate and the

concentration of surfactant in the abscissa. The 24

- h EC50 and 95% confidence l evel were

calculated by Litchfield and Wilcoxon’s method.

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: 24

- hour EC 50 = 1.8 mg/L (effect on glycerol content)

Remarks: None

CONCLUSIONS

RELIABILITY COD E

3

REFERENCE

Utsunomiya, A., T. Watanuki, K. Matsushita, and I. Tomita , “ Toxic Effects of Linear

Alkylbenzene Sulfonate, Quaternary Alkylammonium Chloride and Their Complexes on

Dunaliella sp. and Chlorella pyrenoidosa ”. Environ.Toxicol.Chem. 16(6):124 7

- 1254 ; 1997Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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34 Study 2: Toxicity study of alkyldimethylbenzylammoniumchloride in Chlorella pyrenoidosa

Title: Toxic Effects of Linear Alkylbenzene Sulfonate, Quaternary Alkylammonium Chloride

and their Complexes on Dunaliella sp. and Chlorella pyren oidosa

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Alkyldimethylbenzylammoniumchloride (R = C12

- 14); abbreviated as BM

Remarks: Purity > 97.5%

METHOD

Method/guideline followed: Not stated

Test type: Not stated

GLP: Not stated

Year: circa 1995

Species/strain/supplier: Chlorella pyrenoidosa

Element Basis: area under the curve

Exposure Period: 96 hours

Analytical Monitoring: Not stated

Statistical Methods: Not stated

Method remarks: Chlorella pyrenoidosa was supplied by the Institute of Molecular and

Cellular Bioscience. The precultures of test alga were incubated at 25 +/

- 1 C under continuous

lightening at 140 μ E/m 2 /s and sterile aeration through a 0.2

- mm filter for approximately 7 days.

A modified Bristol medium was used.

The concentration ranges in which inhibitory effects were likely to occur were determined from

range

- finding tests. The 400

- mL culture medium and the algal inoculums taken from a

preculture in the exponential growth phase were added to 500

- mL sterile culture bottles. The

initial algal density was approximately 1 x 10 4 cells/mL. The stepwise graded concentrations of

BM, with more than four concentrations with two replicates each , were added to each test

solu tion. The test solutions were incubated at 24+/

- 2 C under continuous lightening at 140

μ E/m 2 /s with slow continuous shaking (100 rpm) for 96 h using controlled environmentDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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35 incubator shaker. A 100

- to 10

- mL portion of each test solution was centrifuged a t 1,900 g for

15 min at 5 C. Chlorophyll

- a concentration, an indicator of cell growth, was measured every 24

h from the start of this test to 96 h by Parsons and Strickland’s method.

The growth curves for each concentration of test substance and for the control were obtained by

plotting the chlorophyll

- a concentration in the ordinate and the incubation time in the abscissa.

Following OECD test guidelines, the areas under the growth curves were calculated every 24 h

until 96 h, and the percentage of growt h inhibition was calculated from the ratio of the difference

between the area under the growth curve at each substance concentration. The 96

- h EC50 and

95% confidence level were calculated by Litchfield and Wilcoxon’s method.

RESULTS

Nominal concentrat ions: Not stated

Measured concentrations: Not stated

Element value: EC50 = 0.67 mg/L

Remarks: None

CONCLUSIONS

RELIABILITY CODE

2

REFERENCE

Utsunomiya, A., T. Watanuki, K. Matsushita, and I. Tomita

Toxic Effects of Linear Alkylbenzene Sulfonate, Quaternary Alkylammonium Chloride and

Their Complexes on Dunaliella sp. and Chlorella pyrenoidosa

Environ.Toxicol.Chem. 16(6):1247

- 1254

1997Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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36 Study 3: Toxicity study of Hyamine 3500 in Cladophora glomerata

Title: Interpretation of Ultrastructral Cha nges in Cladophora glomerata Resulting from

Hyamine Toxicity

The study is: Adequate Not Adequate

This is not a guideline study and provides no LD50.

TEST SUBSTANCE

Identity: Hyamine 3500, synonym for quaternary amm onium compounds, benzyl

- C12

- 16

- alkyldimethyl, chlorides

Remarks: 80% concentrate in ethanol

METHOD

Method/guideline followed: Not stated

Test type: Not stated

GLP: Not stated

Year: circa 1992

Species/strain/supplier: Cladophora glomerata

Element Basis: Not stated

Exposure Period: 4 days

Analytical Monitoring: Not stated

Statistical Methods: Not stated

Method remarks: The test filamentous species, Cladophora glomerata (L.) Kutz. (UTTC #13)

was obtained from the University of Toronto Cult ure Collection (UTCC). The alga was

originally isolated from the Thames River, Ontario. The algal culture was maintained in Bold’s

Basal Medium (BBM) (Hutchinson and Stokes 1975) supplemented with a vitamin mix (B 12 , biotin and thiamine), and 5 mg/L Si a s NaSiO 3 x 9H 2 O

Chlorella fusca Shihira et Krauss, a unicellular alga, obtained from the laboratory at the Canada

Centre for Inland Waters, Burlington, Ontario, was the other species used in the tests.

Hyamine 3500, was purchased from the Rohm and Haas C ompany. This algicide is an 80%Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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37 concentrate in ethanol, containing the active ingredient n

- alkyl (80% tetradecyl, 40% dodecyl

and 10% hexadecyl) dimethyl benzyl ammonium chloride. The molecular weight of the

chemical is 359.6. Stable and nonvolatile, it has been recommended by the company (Rohm and

Haas 1978) as a disinfectant in swimming pools at low concentrations.

Algal assays were conducted in duplicate in 250

- mL Erlenmeyer flasks containing 100 mL BBM

solution. The toxicity range of Hyamine for Cl adophora was tested at the beginning of the

study. In the final assays, the Hyamine concentrations were set at 0.2, 0.3, 0.4, 0.5, 0.8 and 1.0

mg/L. Zero Hyamine concentration was used as a control. About 0.5 g (wet weight) of

Cladophora filament was us ed as the inoculums. The cultures were incubated for 4 days at 20 C

in an environmental chamber where the light and dark cycle was set at 12:12 and the light

intensity was 60 μ Ein/m 2 /sec.

On day 4, a small amount of plant material was removed from each concentration for

morphological examination using a light microscope. One set of samples was put aside for

electron microscopic preparation; the other set was incubated for another 3 weeks for further

morphological evaluations. These tests were repeated at the end of the experiment.

For electron microscope studies, Cladophora filaments were fixed in 4% (cacodylate

- buffered)

glutaraldehyde for 6 hr and then postfixed in 2% (cacodylate

- buffered) osium tetroxide for 1 hr.

The dehydration ethanol series was 30%, 50%, 70%, 90%, 95% and 100%.

For infiltration, the Spurr’s medium (Hayat 1989) to ethanol ratios were 1:3, 1:2, and 2:3 v/v.

The Cladophora filaments were then embedded in 100% Spurr’s medium in an aluminum dish.

The samples were polymerized at 70 C overnight.

A dissecting microscope was used to locate the apical cells on the plastic. After they were

marked, small columns of specimens were cut out with a jeweller’s saw. Thin sections were

prepared with a glass knife on a microtome. These se ctions were then stained with uranyl

acetate and lead citrate. Observations were made using a Siemens electron microscope.

To assess the effect of Hyamine on Chlorella cells, a conventional method based on growth

measurements was used (Miller et al. 1978 ). A Chlorella pre

- culture was prepared. The

Hyamine concentrations used were the same as those employed in the Cladophora assays. On

day 7, when the pre

- culture reached its logarithmic growth phase, the Chlorella cells were ready

for inoculation. The initial cell concentration in the test solution was 40 x10 3 cells/L. After

inoculation, the culture flasks were mounted on a platform shaker and incubated for 14 days in a

growth chamber. Cells numbers were enumerated at 4 day intervals and at the end of the

experiment when the algal biomass reached its growth plateau.

RESULTS

Nominal concentrations: 0.2, 0.3, 0.4, 0.5, 0.8 and 1.0 mg/LDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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38 Remarks:

Hyamine conc (mg/L) Chlorella fusca avg. yield (10 5 cells/mL) after

14 days

control 14.5

0.15 13.6

0 .20 15.3

0.30 13.9

0.40 no data

0.50 14.6

0.60 10.8

0.80 no growth

1.00 no growth

CONCLUSIONS

RELIABILITY CODE

3

REFERENCE

Wong, S.L., and J.F. Wainwright . “ Interpretation of Ultrastructural Changes in Cladophora

glomerata Resulting from Hyami ne Toxicity ”. Bull.Environ.Contam.Toxicol. 52(3):325

- 332 ;

1994Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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39 Study 4. Toxicity study of ADBAC in green algae

Title: Environmental Assessment of an Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

Based Molluscicide Using Laboratory Tests.

The stu dy is: Adequate Not Adequate

This study was considered inadequate due to deviations from accepting testing guidelines.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 50% (2.5 mg/L) plus Bentonite Clay at concentrations of 0:0, 2.5:25, 2.5:37.5, 2.5:50,

and 2.5:75 mg/L

METHOD

Method/guideline followed: Not stated

Test type: Static

- renewal

GLP: Not stated

Year: Not stated

Species/strain/supplier: Green algae ( Selenastrum capricornutum )

Element Basis: Not stated

E xposure Period: 96 hours

Analytical Monitoring: Not stated

Statistical Methods: Not stated

Method remarks: None

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LOAEC = 2.5:25 for growth; NOAEC = 2. 5:37.5 for growthDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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40 Remarks:

Supplemental study

Open literature

Assess detoxification of a.i.

CONCLUSIONS

RELIABILITY CODE

3

– deviations from guideline include photoperiod and lack of detailed information

REFERENCE

Dobbs, M.G., D.S. Cherry, J.C. Sco tt, and J.C. Petrille. 1995. Environmental Assessment of an

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Based Molluscicide Using Laboratory

Tests. Published data. Proceedings of the Fifth International Zebra Mussel and Other Aquatic

Nuisance Organi sms Conference, Toronto, Canada.

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41 B

- 4. CHRONIC TOXICITY TO AQUATIC ORGANISMS

Study 1. Chronic toxicity study of ADBAC to fathead minnows

Title: Daily Static

- Renewal Early Life Stage Toxicity Tes t of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) to Fathead Minnows. Project No. SC890057

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 30% ai

METHOD

Method/guideline followed: OPPTS 850.1400

GLP: Not stated

Year study performed: Not stated

Test type: Static

- renewal

Species/strain/supplier: Fathead minnow ( Pimephales promelas )

Analytical monitoring: Not stated

Exposure period: 34 days

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Early life stage test

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LOAEC = 0.0759 mg/L a.i.; NOAEC = 0.0322 mg/L a.i.; MATC = 0.0494 a.i

.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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42 Remarks: Not stated

CONCLUSIONS

None stated.

RELIABILITY CODE

2

REFERENCES

MRID 423021

- 02 . McIntyre, D.O. and H.O. Pate. 1992. Daily Static

- Renewal Early Life Stage

Toxicity Test of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) to Fathead M innows.

Project No. SC890057. Unpublished data. Conducted by Battelle Columbus Operations for

ADBAC Quat Joint Venture/Chemical Specialties Manufacturers Assocation.

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43 Study 2: Chronic static

- renewal 21

- day toxicity study of ADBAC in Daphnia magna

Title: Daily Static

- Renewal Chronic 21

- day Toxicity Test of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) to Daphnia magna . Study No. SC890056

The study is: Adequate Not Adequate

T his study was considered inadequate due to high mortality in the control group.

TEST SUBSTANCE

Identity: ADBAC

Remarks: 3 0% ai

METHOD

Method/guideline followed: OPPTS 850.1300

GLP: Not stated

Year study performed: Not stated

Test type: Static

- Re newal

Species/strain/supplier: Water flea ( Daphnia magna )

Analytical monitoring: Not stated

Exposure period: Not stated

Number of animals/sex/dose: Not stated

Statistical methods used: Not stated

Method remarks: Numerous deviations from guideline include MATC not established

RESULTS

Nominal concentrations: Not stated

Measured concentrations: Not stated

Element value: LOAEC = Not determined; NOAEC 0.00415 mg/L a.i.; MATC = Not

DeterminedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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44 Remarks: Not stated

CONCLUSIONS

None stated.

RELIA BILITY CODE

3

- High control mortality

REFERENCES

MRID 423021

- 01. McIntyre, D.O. and H.O. Pate. 1992. Daily Static

- Renewal Chronic 21

- day

Toxicity Test of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) to Daphnia magna

. Study No. SC890056. Unpublis hed data. Conducted by Batalle Columbus Division for ADBAC

Quat Joint Venture/Chemical Specialties Manufacturers Assocation.

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45 B

- 5. ACUTE TOXICITY STUDIES

Study 1 : Acute oral toxicity study of ADBAC in rats

Summary of en dpoint: Adequate

Title : An Acute Oral Toxicity Study in Rats with BQ 451

- 8: Lab Project Number: 3192.32

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity : ADBAC

Remarks : Purity 82.26%

METHOD

Method /guideline followed: 870.1100

Type: Acute oral

GLP : Not stated

Year : Not stated

Species/Strain: Rat

Sex: Both

No. of animals per sex per dose: Not stated

Vehicle : Not stated

Route of administration: Oral

Method remarks:

Females: 0, 100, 25 0, 500 or 510 mg/kg

Males: 0, 500, 510, 525, 600 or 750 mg/kg

Rats (5/sex/dose)Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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46 RESULTS

LD50 value:

304.5 mg/kg (both sexes combined)

510.9 mg/kg (males)

280.8 mg/kg (females)

Number of deaths at each dose level: Two 200 mg/kg females, four 500 mg/kg females, three

males, and four females in the 510 mg/kg group and all males in the 525, 600, and 750 mg/kg

groups were dead by Day 6.

Remarks: Two 200 mg/kg females, four 500 mg/kg females, three males, and four females in

the 510 mg/kg group and all mal es in the 525, 600, and 750 mg/kg groups were dead by Day 6.

Breathing abnormalities, decreased activity, wobbly gait, salivation, apparent hypothermia,

soft/mucoid stools, diarrhea, decreased/no defecation, fecal/urine stain, piloerection, rough

haircoat , hunched postures, dehydration, ocular discharge, decreased food consumption, and/or

dark material around the facial area were noted from most of the rats with recovery by Day 13 or

earlier. Two surviving 510 mg/kg males lost weight during the first week of study, but gained

weight during the second week. All other surviving rats gained weight during the study. The

decedents had abnormal content and/or reddened mucosa in the digestive tract, dark red thymus,

and/or fluid contents in the thoracic cavity, abnormal content in the small intestines and/or

thickened stomach mucosa.

CONCLUSIONS

Toxic Category II

RELIABILITY CODE

2

REFERENCES

45109204 (MRID) Bonnette, K. (1998) An Acute Oral Toxicity Study in Rats with BQ 451

- 8:

Lab Project Number: 319 2.32. Unpublished study prepared by Springborn Laboratories. 90 p.

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47 Study 2: Acute dermal toxicity study of ADBAC in rats

Title : Acute Dermal Toxicity Study in Rats: Albemarle BQ451

- 8 Biocide: Lab Project Number :

7466:P322

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity : ADBAC

Remarks : Purity 82.26%

METHOD

Method/guideline followed: 870.1200

Type: Acute dermal

GLP : Not stated

Year : Not stated

Specie s/Strain: Rat

Sex: Both

No. of animals per sex per dose: Not stated

Vehicle : Not stated

Route of administration: Dermal

Method remarks:

0, 500, 1000 or 2000 mg/kg

Rats (5/sex/dose)

RESULTS

LD50 value:

930 mg/kg (combined)

1100 mg/kg (males)

704 mg/kg (females)

Number of deaths at each dose level: Five 2000 mg/kg females were found dead on Day 1.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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48 One 500 mg/kg female, one male and four females in the 1000 mg/kg group, and five 2000

mg/kg were found dead by Day 4.

Remarks: Five 2000 mg/kg femal es were found dead on Day 1. One 500 mg/kg female, one

male and four females in the 1000 mg/kg group, and five 2000 mg/kg were found dead by Day 4.

Irregular respirations, hunched postures, hypoactivity, coldness to the touch, reduced fecal

volume, tremo rs, ataxia, and/or dyspnea were noted for the decendents prior to death.

Hypoactivity, hunched postures, reduced fecal volume, and/or irregular respiration were noted

for some of the surviving rats with recovery by Day 2. Erythema and edema were noted at dose

site from most of the rats. Eschar was also noted at the dose site from surviving rats. All

surviving rats had normal body weight gains. No gross abnormalities were noted from the

surviving rats and one female decedent in the 1000 mg/kg group. Th e other decedents had

slightly/moderately red lungs, discolored livers, and/or red/black/green/yellow intestines.

CONCLUSIONS

Toxic Category II

RELIABILITY CODE

2

REFERENCES

45109202 (MRID) Moore, G. (1999) Acute Dermal Toxicity Study in Rats: Albe marle BQ451

- 8

Biocide: Lab Project Number: 7466:P322. Unpublished study prepared by Product Safety Labs.

25p.

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49 Study 3: Acute inhalation toxicity study of ADBAC in rats

Title : Acute Inhalation Toxicity Study in Rats: Alb emarle BQ451

- 8 Biocide: Lab Project

Number: 7467: P330

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity : ADBAC

Remarks : Purity 82.26%

METHOD

Method/guideline followed: 870.1300

Type: Acute inhalation

GLP : Not stated

Year : Not stated

Species/Strain: Rat

Sex: Not stated

No. of animals per sex per dose: Not stated

Vehicle : Not stated

Route of administration: Inhalation

Method remarks:

0.054 or 0.51 mg/L

Rats (5/sex/dose)

RESULTS

LC 50 value: 0 .054 < LC50 < 0.51 mg/L

Number of deaths at each dose level: 0.054 mg/L group: All animals survived; 0.51 mg/L

group: All animals died.

Remarks: 0.054 mg/L group: All animals survived. Animal displayed ocular and nasalDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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50 discharge, irregular respiration , dyspnea, hunched posture, and hypoactivity. Irregular respiration

and/or hypoactivity persisted in several rats upon removal from the exposure chamber and some

animals also developed facial staining or reduced fecal volume. All rats recovered from the

a bove symptoms by Day 2 and appeared active and healthy for the remainder of the study,

gaining bodyweight over the entire 14

- day observation period. No gross abnormalities were

noted in animals when necropsied.

0.51 mg/L group: All animals died. During exposure, animals exhibited ocular and nasal

discharge, irregular respiration, dyspnea, gasping, hunched posture, and hypoactivity prior to

death. Gross necropsy of one animal revealed discoloration and edema of the lungs. Gross

abnormalities were not no ted in the other animals.

CONCLUSIONS

Toxicity Category II

RELIABILITY CODE

2

REFERENCES

44885201 (MRID) Wnorowski, G. (1999) Acute Inhalation Toxicity Study in Rats: Albemarle

BQ451

- 8 Biocide: Lab Project Number: 7467: P330. Unpublished study pre pared by Product

Safety Labs. 30 p.

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51 B

- 6. SKIN IRRITATION STUDY

Study 1: Skin irritation study of ADBAC in rabbits

Title: Primary Skin Irritation Study in Rabbits: Albemarle BQ451

- 8 Biocide: Lab Project

Number: 7468: P326

TEST SUBSTANCE

Identity: ADBAC

Remarks: Purity 82.26%

METHOD

Method/guideline followed: 870.2500

GLP (Y/N): Not stated

Species/strain: Rabbit

Sex (males/females/both): Female

Number of animals/sex/dose: Not stated

Volume administered: 0.5 mL BQ451

- 8, 40 hours

Test condition: Not stated

RESULTS

Corrosive . The rabbit had well

- defined erythema one hour after patch removal. The erythema

intensified to severe by 24 hours and persisted through 72 hours. Moderate edema was noted in

the rabbit o ne hour after patch removal, but reduced to slight by 24 hours through 72 hours . The

application site showed superficial eschar by 24 through 48 hours and signs of dermal corrosion

by 72 hours. The primary dermal irritation index was 5.8.

CONCLUSIONS

T oxic Category I

RELIABILITY CODE

2

REFERENCESDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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52 45109201 (MRID) Moore, G. (1999) Primary Skin Irritation Study in Rabbits: Albemarle

BQ451

- 8 Biocide: Lab Project Number: 7468: P326. Unpublished study prepared by Product

Safety Labs. 15 p.

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53 B

- 7. DERMAL SENSITIZATION STUDY

Study 1: Dermal sensitization study of ADBAC in guinea pigs

Title: Dermal Sensitization Study in Guinea Pigs (Buehler Method): Albermarle BQ451

- 8

Biocide: Lab Project Number: 7469: P328

TEST SU BSTANCE

Identity: ADBAC

Remarks: Purity 82.26%

METHOD

Method/guideline followed: 870.2600

GLP (Y/N): Not stated

Species/strain: Guinea pigs

Sex (male/female/both): Both

Number of animals/sex/dose: 20 test animals, 10 controls; 24 males, 6 females

Dose/concentration: Induction: 0.4 mL of 2% w/w test material in distilled water with occlusive

25 mm Hilltop Chamber for 6 hours once/week, 3 weeks.

Challenge Period: 27 days

Challenge dose: 0.4 mL of 0.5% w/w test material in distilled water under occlu sion for 6 hours.

Control: 0.4 mL of 0.5% w/w test material in distilled water at challenge only

Test condition: Not stated

RESULTS

Faint usually confluent to moderate erythema was noted on all animals after the first induction.

Very faint usually non confluent to moderate erythema was noted on 19/20 animals and severe

erythema was noted on 1/20 animals after the second induction. Faint usually confluent to

severe erythema was noted on all animals after the third induction. Eschar was noted on 2/20

an imals 48 hours after the third induction. Desquamation was noted on one animal 24 hours

after the third induction with resolution by 48 hours. After three weekly inductions, dermal

irritation suggestive of sensitization was not observed on the test anima ls after challenge. The

study report included DNCB positive control study which was carried out within six months of

the current study. The results were appropriate.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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54 CONCLUSIONS

Not a dermal sensitizer.

RELIABILITY CODE

2

REFERENCES

45109203 (MRID) Moore, G. (1999) Dermal Sensitization Study in Guinea Pigs (Buehler

Method): Albermarle BQ451

- 8 Biocide: Lab Project Number: 7469: P328. Unpublished study

prepared by Product Safety Labs. 24 p.

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55 B

- 8. GENETIC TOXICIT Y STUDY

Study 1: Mutagenicity study of ADBAC in the CHO/HGPRT forward mutation assay

Summary of endpoint: Adequate

Title: Mutagenicity Test on Alkyl Dimethyl Benzyl Ammonium Chloride: In the CHO/HGPRT

Forward Mutation Assay: HLA Study No. 10238

- 0

- 435

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks : 80% purity

METHOD

Method/guideline followed: 870.5300

Test Type: HGPRT Assay in CHO cells for forward mutation

Test system: Mammalia n cell, in vitro

GLP (Y/N): Not stated

Year study performed: Not stated

Species/Strain/cell

- type/cell line: Chinese Hamster ovary cells

Metabolic activation: Not stated

Concentrations tested: 0, 1.0, 2.0, 5.0, 10.0, 20.0, 50.0, 100.0, 200.0, 500.0 o r 5000.0 μg/mL,

with and without metabolic activation

Remarks: None

RESULTS

Overall results: Negative

Cytotoxic concentration: Not statedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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56 Remarks: Mutant frequencies of all cultures treated with the test material were within the

acceptable range for background mutant frequencies (0 to 15 x 10

- 6 ). In all of the assays, no

culture had a mutant frequency that was statistically elevated over background levels and greater

than 15 x 10

- 6 . Three toxic cultures in one nonactivation trial did achieve statist ical significance.

The significant mutant frequencies were within the acceptable background range and were not

confirmed at equitoxic dose levels I the independent nonactivation trial. The significant cultures,

in that one trial were apparently due to no rmal assay variation. ADBAC was considered negative

for inducing forward mutations at the HGPRT locus in CHO cells under the S9 metabolic

activation and nonactivation conditions of this assay.

CONCLUSIONS

A D B AC showed negative evidence of mutagenicity i n Chinese Hamster ovary cells.

RELIABILITY CODE

2

REFERENCE

41012701 (MRID) Young, R. (1989) Mutagenicity Test on Alkyl Dimethyl Benzyl Ammonium

Chloride: In the CHO/HGPRT Forward Mutation Assay: HLA Study No. 10238

- 0

- 435.

Unpublished study prepared by Hazleton Laboratories America, Inc. 67 p.

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57 B

- 9. CHROMOSOMAL ABERRATIONS STUDY

Study 1: Micronucleus test of ADBAC

Summary of endpoint: Adequate

Title: Assessment of the Mutagenic Activity of Hya

- mine 3500 in th e Mouse Micronucleus Test:

Lab. No. 10753

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% purity

METHOD

Method/guideline followed: 870.5385

Test Type: In vivo bone marrow chromos ome aberration assay

Test system: In vivo

GLP (Y/N): Not stated

Year study performed: Not stated

Species/Strain/cell

- type/cell line: mouse bone marrow cells

Metabolic activation: Not stated

Concentrations tested: Single dose of 400 mg/kg, sacrifice d at 24, 48 or 72 hours later

Remarks:

Mice (5/sex/group)

Solvent control: deionized water

Positive control: Cyclosphosphamide (CP, 30 mg/kg)

RESULTS

Overall results: Negative

Cytotoxic concentration: Not statedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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58 Remarks: One mouse of the 72

- hour gr oup was found dead on the third day after treatment. The

PCE/NCE ratio was reduced in all test groups (as well as the positive controls), but no alteration

in MN from solvent control value was found in any timed test group. By contrast, the CP

- group

eviden ced a significant increase in MN

- PCE.

CONCLUSIONS

A D B AC showed negative evidence of mutagenicity in an in vivo bone marrow chromosome

aberration assay

.

RELIABILITY CODE

2

REFERENCE

40311101 (MRID) Kallerson, T. (1985) Assessment of the Mutagenic Act ivity of Hya

- mine

3500 in the Mouse Micronucleus Test: Lab. No. 10753. Un

- published study prepared by

Scantox Labs Ltd. 17p

43037701 (MRID) Schoenig, G. (1993) Response to EPA Data Evaluation Review for Study

Entitled: “Chromosome Aberrations in vivo

— Mo use Micronucleus Test”: Lab Project Number:

10753. Unpublished study prepared by SCANTOX Biologisk Laboratorium A/S. 7 p.

(EPA

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59 Study 2: Unscheduled DNA Synthesis Assay of ADBAC

Title: Alkyl Dimethyl Benzyl Ammonium Chloride ( ADBAC) in the Rat Primary Hepatocyte

Unscheduled DNA Synthesis Assay: An addendum: Lab Project Number: 10238

- 0

- 447

TEST SUBSTANCE

Identity: ADBAC

Remarks: 80% purity

METHOD

Method/guideline followed: 870.5550

Test Type: Unscheduled DNA synthesis ass ay

Test system: Mammalian cells

GLP (Y/N): Not stated

Year study performed: Not stated

Species/Strain/cell

- type/cell line: Rat hepatocyte cells

Metabolic activation: Not stated

Concentrations tested: Tritiated thymidine (38Ci/mmol) for 18.8 hours t ogether with 0.538,

1.08, 2.15, 4.31, 5.38, 6.46, 7.00, 7.54, 8.07 or 8.61 μg/mL ADBAC

Remarks:

Solvent control: deionized water

Positive control: AAF, 0.10 μg/mL

RESULTS

Overall results: Negative

Cytotoxic concentration: Not stated

Remarks: The te st article was lethal at 8.61 ug/mL, and progressively cytotoxic at doses equal

to or above 4.31 ug/mL. Treatments producing moderate levels of cytotoxicity (62.7% relative

survival and greater) as well as non

- toxic doses were analyzed for UDS. None of th ese

analyzable treatments induced silver grain labeling different from solvent control. In contrast,

the mutagen 2

- AAF induced large increases in nuclear labeling in the absence of significant

toxicity.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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60 CONCLUSIONS

ADBAC showed negative evidence of muta genicity in an unscheduled DNA synthesis assay.

RELIABILITY CODE

2

REFERENCE

42290802 (MRID) McKeon, M. (1989) Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)

in the Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay: An addendum: Lab Project

Numb er: 10238

- 0

- 447. Unpublished study prepared by Hazleton Laboratories America, Inc. 11

p.

42290801 (MRID) McKeon, M. (1992) Genotoxicity Test on Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) in the Assay for Unscheduled DNA Synthesis in Rat Liver

Prima ry Cell Cultures: Lab Project Number: 14778

- 0

- 447. Unpublished study prepared by

Hazleton Washington, Inc. 51 p.

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61 B

- 10. REPEATED

- DOSE TOXICITY STUDIES

Study 1: Repeated

- dose toxicity study of ADBAC in guinea pigs

Summar y of endpoint: Adequate

Title: 21

- Day Dermal Toxicity

– Guinea Pigs, OPPTS 870.3200

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: formulated product

Remarks: 6% ai; ADBAC contained within HS

- sanit izing carpet shampoo at a 1:5 dilution

METHOD

Method/guideline followed: OPPTS 870.3200

GLP: Not stated

Year study was performed: Not stated

Test type: 21

- day dermal toxicity test

Species/strain: Guinea pig (strain not specified)

Sex: Both

Rout e of administration: Dermal

Doses: 1000 mg/kg/day of ADBAC

Exposure period: 24 hours

Frequency of treatment: 5 days per week for 3 weeks

Control group and treatment: Not stated

Post

- observation period: Not stated

Statistical methods: Not stated

Met hod remarks: In a 21

- day dermal toxicity study, a dose of 1000 mg/kg/day (limit dose) ofDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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62 ADBAC, contained within HS

- sanitizing carpet shampoo at a 1:5 dilution, was tested in male

and female guinea pigs, 5 days per week, for 3 weeks. Each exposure was fo r 24 hours to groups

of 5 guinea pigs/sex/dose.

RESULTS

NOAEL and LOAEL:

LOAEL (systemic) = 1000 mg/kg/day based on decreases in body weight in female pigs

NOAEL (systemic) < 1000 mg/kg/day (not achieved)

LOAEL (dermal) = 1000 mg/kg/day based on den uding of the epidermal layer

NOAEL (dermal) not achieved

Actual dose received by dose level by sex: Not stated

Remarks: Over the course of the study, body weight losses of between 6

- 11% were observed in

male and female guinea pigs. There were no reporte d mortalities or clinical signs of toxicity.

Slight reduction in food consumption (2

- 5%) was observed over the course of this study. There

were no significant treatment

- related effects on hematology or clinical chemistry. Histological

examination of the skin showed that the non

- vascularized epidermal layer was denuded, while

the dermal or corium layer and basement membrane appeared normal. There were no treatment

related effects reported on the liver and kidney.

CONCLUSIONS

The Systemic LOAEL = 1000 m g/kg/day, based on decreases in body weight in female guinea

pigs. The Systemic NOAEL < 1000 mg/kg/day (not achieved). The Dermal LOAEL = 1000

mg/kg/day, based on denuding of the epidermal layer. The Dermal NOAEL was not achieved.

RELIABILITY CODE

2

- The study contained several experimental deficiencies but had enough information on dermal

effects to be used for the dermal endpoint determination

REFERENCES

40700700 (MRID)

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63 Study 2. Repeated

- dose dermal toxicity study of ADBAC

Title: Acute Toxicology (EP): HS

- Sanitizing Carpet Shampoo: Project ID: B6

- 27

The study is: Adequate Not Adequate

This study was considered inadequate due to testing at a non

- standard duration (< 28

- days).

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81% ai

METHOD

Method/guideline followed: OPPTS 870.3200

GLP: Not stated

Year study was performed: Not stated

Test type: 21

- day dermal toxicity test

Species/strain: Guinea pig (strain not specified)

Se x: Both

Route of administration: Dermal

Doses: 0, 500 , and 1000 mg/kg /day

Exposure period: 24 hours

Frequency of treatment: 5 days per week for 3 weeks

Control group and treatment: Not stated

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: A 1:5 dilution of HS

- sanitizing carpet shampoo (containing 6% didecyl

ammonium chloride and 4% alkyl dimethyl benzyl ammonium chloride) was applied to a 2 inch

square of shaved dorsal trunk of 5 male and 5 female guinea pigs a t 500 mg/kg, five days aDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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64 week, for 21 days. Each exposure was for 24 hours.

RESULTS

NOAEL and LOAEL:

Systemic toxicity:

NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on decreases in body weight in females

Dermal toxicity:

NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on denuding of the epidermal layer

Actual dose received by dose level by sex: Not stated

Remarks: Signs of skin irritation were noted during the second week of treatment and the report

stated that the response intensified du ring the third week of treatment. Body weight was

decreased in treated males and females by 7% and 11% vs. untreated animals at week 3 at 1000

mg/kg. Results of hematology and clinical chemistry measurements indicated a slight elevation

of basophils and eosinophils as well as a slight elevation of SGPT and SGOT but statistics were

not performed on these data. Histologically, the skin irritation was described as denuded non

vascularized epidermal layer at the application site.

CONCLUSIONS

The 500 mg/k g/day value could be considered a provisional NOAEL as slight effects were still

observed on the skin and the report did not represent the data on this effect at this dose but it

likely that a true NOAEL would not be vary far below this level for dermal ef fects.

RELIABILITY CODE

3

- This study also contained several deficiencies including lack of several experimental details

(no information on dose solution, stability and homogeneity), and missing individual animal data

for body weight, clinical observatio ns, hematology, clinical chemistry, organ weights, gross

pathology and histopathology.

REFERENCES

41105801 (MRID) Rose, G. (1989) Acute Toxicology (EP): HS

- Sanitizing Carpet Shampoo:

Project ID: B6

- 27. Unpublished study prepared by Envirocon. 36 p.

40565301 (MRID)

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65 Study 3: Repeated

- dose dermal toxicity study of ADBAC in rats

Title: Ninety

- day Subchronic Dermal Toxicity Study with Alkyl Dimethyl Benzyl Ammonium

Chloride (ADBAC) in Rats: Lab Project I.D.: 52

- 623

T he study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09% a.i.

METHOD

Method/guideline followed: 870.3250

GLP: Not stated

Year study was performed: Not stated

Test type: 90

- day dermal toxicity study

Species/strain: Sprague

- Dawley rats

Sex: Both

Route of administration: dermal (to clipped backs)

Doses: 0, 2, 6 or 20 mg/kg/day (as 0.1, 0.3 and 1.0% solutions at a dose volume of 2 ml/kg)

Exposure period: 6 to 8 hours

Frequency of tre atment: 5 days per week for 13 weeks.

Control group and treatment: a control was included (0 mg/kg/day)

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a 90

- day dermal toxicity study, ADBAC (81.09% a.i.) was app lied at dose

levels of 0, 2, 6 or 20 mg/kg/day (as 0.1, 0.3 and 1.0% solutions at a dose volume of 2 ml/kg) to

the clipped backs of Sprague

- Dawley rats for 6

- 8 hours per day, 5 days per week, for 13 weeks.

Although higher doses were tested in a preliminar y range

- finding study (6, 20, 60, 120 and 200

mg/kg/day), the high dose selected for the main study (20 mg/kg/day) was chosen on the basisDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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66 that higher concentrations produced skin irritation that was considered greater than slight.

RESULTS

NOAEL and LOAE L:

NOAEL (systemic and dermal) = 20 mg/kg/day

Actual dose received by dose level by sex: Not stated

Remarks: A significant and dose

- related decrease in reticulocyte count was observed in the 6

-

and 20

- mg/kg/day females. Decreases in reticulocyte count are normally associated with

regenerative responses to anemia. However, no evidence of anemia was seen in other

hematological parameters. Furthermore, the decreased levels in treated females were similar to

the levels observed in control males. Thus, t he decreasing reticulocyte count was most likely not

a biologically significant finding.

A significant increase in hyperkeratosis was observed in treated skin of high dose females, but

this lesion was also observed in increased incidence in male rats at a ll doses including controls.

CONCLUSIONS

The NOAEL for systemic and dermal effects was determined to be 20 mg/kg/day

RELIABILITY CODE

2

REFERENCES

41499601 (MRID) Gill, M.; Wagner, C. (1990) Ninety

- day Subchronic Dermal Toxicity Study

with Alkyl Dime thyl Benzyl Ammonium Chloride (ADBAC) in Rats: Lab Project I.D.: 52

- 623.

Unpublished study prepared by Union Carbide Bushy Run Research Center. 264 p.

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67 Study 4: Repeated

- dose dietary toxicity study of ADBAC in rats

Titl e: Ninety

- day Dietary Toxicity Study with Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) in Rats: Project ID:51

- 503.

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Alkyl dimethyl benzyl ammonium chl oride ( ADBAC)

Remarks: 79.7% a.i.

METHOD

Method/guideline followed: 870.3100

GLP: Not stated

Year study was performed: Not stated

Test type: Subchronic oral toxicity

Species/strain: Rats

Sex: Both

Route of administration: Dietary

Doses: 0 , 100, 500, 1000 (0, 6.3, 31.2 and 62.0 mg/kg/day for males and 0, 7.9, 38.3 and 76.7

mg/kg/day for females), 4000 or 8000 ppm

Exposure period: 13 weeks

Frequency of treatment: Daily

Control group and treatment: 0 ppm

Post

- observation period: Not st ated

Statistical methods: Not stated

Method remarks: In a subchronic oral toxicity study in rats, male and female rats (15/sex/dose)

were administered ADBAC (79.7% a.i.) in the diet for 13 weeks at dose levels of 0, 100, 500,

1000, 4000 or 8000 ppm.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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68 RE SULTS

NOAEL and LOAEL:

NOAEL (systemic; males) = 500 ppm (31.2 mg/kg/day)

LOAEL (systemic; males) = 1000 ppm (62.0 mg/kg/day) based on decreased weight gain

NOAEL (systemic; females) = 1000 ppm (76.7 mg/kg/day)

LOAEL (systemic; females) = 4000 ppm (>76. 7 mg/kg/day) based on increased mortality,

decreased body weight gain and food consumption and increased lesions in females

Actual dose received by dose level by sex: 0, 6.3, 31.2 and 62.0 mg/kg/day for males and 0,

7.9, 38.3 and 76.7 mg/kg/day for female s for 0, 100, 500 and 1000 ppm, respectively. Increased

mortality at the two highest dose levels did not allow for daily compound consumption to be

calculated.

Remarks: Increased mortality was observed at the 4000 and 8000 ppm dose groups in both

sexes. Decreased body weight, weight gain, food consumption and increased incidence of

microscopic lesions [congestion and edema of the G.I. tract, hemorrhaging of the lungs and

brain] were also observed in males and females at 4000 ppm ]

.

CONCLUSIONS

The sys temic NOAEL for males is 500 ppm and for females is 1000 ppm, based upon decreased

body weight and weight gain in males at 1000 ppm, and increased mortality, decreased body

weight gain and food consumption, and increased lesions in females at 4000 ppm.

RE LIABILITY CODE

2

– This study is classified as acceptable.

REFERENCES

40746601 (MRID) Van Miller, J.; Weaver, E. (1998) Ninety

- day Dietary Toxicity Study with

Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in Rats: Project ID:51

- 503.

Unpublished study prepared by Bushy Run Re

- search Center. 300p.

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69 Study 5.

Title: Evaluation of ADBAC in a One

- Year Chronic Dietary Toxicity Study in Dogs: Lab

Project Number: 638

- 004

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81% purity

METHOD

Method/guideline followed: 870.4100

GLP: Not stated

Year study was performed: Not stated

Test type: Chronic toxicity

Species/strain: Beagle dogs

Sex: Both

Route o f administration: diet

Doses: 0, 3.79, 13.1 or 33.8 mg/kg/day in males and 0, 3.67, 14.6 or 38.6 mg/kg/day in females

(1, 120, 400 or 1200 ppm)

Exposure period: one year

Frequency of treatment: daily

Control group and treatment: 0 mg/kg/day

Post

- obs ervation period: Not stated

Statistical methods: Not stated

Method remarks: In a chronic toxicity study in dogs, groups of 4 male and female beagle dogs

per group received either 0, 120, 400 or 1200 ppm (0, 3.79, 13.1 or 33.8 mg/kg/day in males and

0, 3.67, 14.6 or 38.6 mg/kg/day in females) alkyl dimethyl benzyl ammonium chloride [ADBAC,

80% a.i.] as a direct dietary admix for one year.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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70 RESULTS

NOAEL and LOAEL:

NOAEL (m/f) = 3.79 / 3.67 mg/kg/day

LOAEL (m/f) = 13.1 / 14.6 mg/kg/day based on reduc ed body weight

Actual dose received by dose level by sex: Not stated

Remarks: Systemic toxicity was observed at 400 ppm and above in female dogs and at 1200

ppm in males as reduced body weight gain (approximately 10% reduction) and 52 weeks of

exposure. Food consumption was decreased in the 1200 ppm males and females for the entire

study period (approximately 15% reduction in males and 5% reduction in females).

CONCLUSIONS

Based on the data in this study, the Systemic Toxicity NOAEL was 120 ppm (3.79 mg/kg/day in

males, 3.67 mg/kg/day in females) and the LOAEL was 400 ppm (13.1 mg/kg/day in males, 14.6

mg/kg/day in females) based on reduced body weight.

RELIABILITY CODE

2

REFERENCES

43221101 (MRID) Goldenthal, E. (1994) Evaluation of ADBAC in a O ne

- Year Chronic Dietary

Toxicity Study in Dogs: Lab Project Number: 638

- 004. Unpublished study prepared by

International Research and Development Corp. 355 p.

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71 B

- 11. CARCINOGENICITY STUDIES

Study 1. Chronic dietary on cogenicity study of ADBAC in mice

Title: Chronic Dietary Oncogenicity Study with Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) in Mice: Lab Project Number: 53

- 515

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Alkyl dimethyl benzyl ammonium chloride ( ADBAC)

Remarks: 81% purity

METHOD

Method/guideline followed: 870.4200

GLP: Not stated

Year study was performed: Not stated

Test type: Carcinogenicity

Species/strain: CD

- 1 mice

Sex: 60/sex/dos e

Route of administration: diet

Doses: nominal doses of 14.9, 73.4 and 229.3 mg/kg/day in males; 17.8, 92.1 and 288.6

mg/kg/day in females (0, 100, 500, or 1500 ppm)

Exposure period: 78 weeks

Frequency of treatment: daily

Control group and treatment : 0 mg/kg/day

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a carcinogenicity study in mice, ADBAC (81% purity) was administeredDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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72 in the diet to male and female CD

- 1 (60/sex/dose) at levels of 0, 100, 500 or 15 00 ppm for 78

weeks (nominal doses of 14.9, 73.4 and 229.3 mg/kg/day in males; 17.8, 92.1 and 288.6

mg/kg/day in females).

RESULTS

NOAEL and LOAEL:

NOAEL (m/f) = 229.3 / 288.6 mg/kg/day

LOAEL (m/f) = 73.4 / 92.1 mg/kg/day , based on decreased body wei ght

Actual dose received by dose level by sex: Not stated

Remarks: No significant differences in the incidence of mortality were observed in treated

animals versus controls. No clinical signs of toxicity were observed at any dose level tested.

Signifi cant reductions in group mean body weight were observed at the high dose in male and

female mice throughout the treatment period with no significant reduction in food intake. There

were no significant treatment

- related effects on organ weights, macroscopi c or microscopic

pathology in treated mice at any dose level.

CONCLUSIONS

ADBAC was negative for carcinogenicity in this study. The Systemic LOAEL = 1500 ppm in

male and female mice (229.3 / 288.6 mg/kg/day), based on reduced body weight. The Systemi c

NOAEL = 500 ppm in male and female mice (73.4 / 92.1 mg/kg/day).

RELIABILITY CODE

2

REFERENCES

41765201 (MRID) Gill, M.; Hermansky, S.; Wagner, C. (1991) Chronic Dietary Oncogenicity

Study with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in Mic e: Lab Project

Number: 53

- 515. Unpublished study prepared by Bushy Run Research Center. 1083 p.

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73 Study 2. Chronic dietary toxicity/oncogenicity study of ADBAC in rats

Title: Chronic Dietary Toxicity/Oncogenicity Stud y with Alkyl Dimethyl Benzyl Ammonium

Chloride (ADBAC) in Rats: Lab Project Number: 53

- 543

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Alkyl dimethyl benzyl ammonium chloride ( ADBAC)

Remarks: 81% p urity

METHOD

Method/guideline followed: OPPTS 870.4300

GLP: Not stated

Year study was performed: Not stated

Test type: Chronic Toxicity / Carcinogenicity in Rats

Species/strain: Sprague

- Dawley rats

Sex: Both

Route of administration: Dietary

Doses: 0, 300, 1000 or 2000 ppm (nominal doses of 13, 44 and 88 mg/kg

- bw/day in males; 17,

57 and 116 mg/kg

- bw/day in females)

Exposure period: 104 weeks

Frequency of treatment: Daily

Control group and treatment: a control group was included (0 mg/kg

- bw/day)

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a chronic toxicity / carcinogenicity study, ADBAC (81% purity) was

administered in the diet to groups of male and female Sprauge

- Dawley rats (50/sex/dose) at dose

levels of 0, 30, 1000 and 2000 ppm (nominal doses of 13, 44 and 88 mg/kg/day in males; 17, 57Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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74 and 116 mg/kg/day in females) for 104 weeks.

RESULTS

NOAEL and LOAEL:

NOAEL (m/f) = 44 / 57 mg/kg

- bw/day

LOAEL (m/f) = 88 / 116 mg/kg

- bw/day base d on decreased body weight and weight gain

Actual dose received by dose level by sex:

Remarks: Significant decreases in group mean body weight were observed in male rats at the

2000 ppm dose level during weeks 1

- 26 of the study and then sporadically the reafter. Body

weights of high dose female rats were also significantly decreased during weeks 1

- 60 of the

study. Body weight gain was decreased 11% on average in high dose males and 14% in high

dose females. There were no significant treatment

- related e ffects on clinical chemistry,

hematology, or urinalysis. No treatment

- related non neoplastic gross or microscopic lesions

were evident in any of the treated groups of rats. There was no evidence of carcinogenicity of

ADBAC in this study.

CONCLUSIONS

T he systemic toxicity NOAEL = 1000 ppm, (44 mg/kg/day [M]; 57 mg/kg/day [F]), and the

Systemic toxicity LOAEL = 2000 ppm (88 mg/kg/day [M]; 116 mg/kg/day [F], based on

decreased body weight and weight gain.)

RELIABILITY CODE

2

REFERENCES

41947501 (MRID) Gill, M.; Hermansky, S.; Wagner, C. (1991) Chronic Dietary

Toxicity/Oncogenicity Study with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in

Rats: Lab Project Number: 53

- 543. Unpublished Study prepared by Bushy Run Research

Center. 1671 p.

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75 B

- 12. REPRODUCTIVE TOXICITY STUDIES

Study 1. Two

- generation reproduction study of ADBAC in rats

Summary of endpoint: Adequate

Title: Two

- generation Reproduction Study in Sprague

- Dawley (CD) Rats with Alkyl Dimethyl

Benzyl Amm onium Chloride (ADBAC) Administered in the Diet: Project Report 52

- 52

- 254:

Project Nos. 87

- 37

- 97105; 87

- 37

- 97109.

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09% pure

METHOD

Method/guideline followed: 870.3800

GLP: No

Year study was performed: Not stated

Species/strain: Sprague

- Dawley rats

Sex: Both

Route of administration: diet

Doses: 0, 300, 1000 or 2000 ppm. Mean compound consumption was 20.7, 68.2 and 134.7

mg /kg/day for F0 males, and 25.5, 81.3 and 164.7 mg/kg/day for F0 females. For the F1 males,

mean compound consumption was 19.1, 62.5, and 125.4 mg/kg/day, and 24.8, 78.5 and 157.1

mg/kg/day for F1 females.

Exposure period: 10 weeks for F0 parents; 15 week s for F1 parents

Frequency of treatment: daily

Control group and treatment: 0 mg/kg/dayDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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76 Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a two

- generation reproductive toxicity study in rats, ADBAC (81.09%)

was a dministered in the diet to groups of male and female Sprague

- Dawley rats (28/sex/dose) at

dose levels of 0, 300, 1000 or 2000 ppm over two generations. After 10 weeks of dietary

treatment, F0 parental animals were mated. F1 parental animals were mated af ter 15 weeks of

dietary treatment. Mean compound consumption was 20.7, 68.2 and 134.7 mg/kg/day for F0

males, and 25.5, 81.3 and 164.7 mg/kg/day for F0 females. For the F1 males, mean compound

consumption was 19.1, 62.5, and 125.4 mg/kg/day, and 24.8, 78 .5 and 157.1 mg/kg/day for F1

females.

RESULTS

NOAEL and LOAEL:

NOAEL (Parental) = 146 mg/kg/day

LOAEL (Parental) > 146 mg/kg/day (highest dose tested)

NOAEL (developmental/systemic) = 65.4/79.9 mg/kg/day (M/F)

LOAEL (developmental/systemic) = 130.1/ 160.9 mg/kg/day (M/F) based on reduced pup body

weight and weight gain during lactation

Remarks: There was no treatment

- related mortality in parental animals at any dose level, and

there were no reported signs of clinical toxicity in parental animals. Al though some decrease in

body weight was observed in both generations at the top dose, the significant variability

observed did not qualify this as a treatment

- related effect.

In pups of both generations, mean body weights at the top dose were significantl y reduced during

lactation and post

- weaning periods. There were no adverse effects noted on gestational length,

mating, fertility, or other gestational indices.

CONCLUSIONS

Based on the results of this study, the Parental NOAEL = 146 mg/kg/day, and the Parental

LOAEL > 146 mg/kg/day (highest dose tested). The Developmental/Systemic NOAEL =

65.4/79.9 mg/kg/day (M/F), and the Developmental/Systemic LOAEL = 130.1/160.9 mg/kg/day

(M/F), based on reduced pup body weight and weight gain during lactation [dose s for both the

F0 and F1 pups combined].

RELIABILITY CODE

2

REFERENCESDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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77 41385001 (MRID) Neeper

- Bradley, T. (1990) Two

- generation Reproduction Study in Sprague

Dawley (CD) Rats with Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Administered

in the Die t: Project Report 52

- 52

- 254: Project Nos. 87

- 37

- 9710 5; 87

- 37

- 97109 . Unpublished

study prepared by Bushy Run Research Center. 492 p.

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78 B

- 13. DEVELOPMENTAL TOXICITY STUDY

Study 1. Developmental toxicity gavage st udy of ADBAC in rats

Summary of endpoint: Adequate

Title: Developmental Toxicity Evaluation II of Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) Administered by Gavage to CD Rats: Lab Project Number: 91N0031

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09% ai

METHOD

Method/guideline followed: 870.3700

GLP: Not stated

Year study was performed: Not stated

Species/strain: Sprague

- Dawley rats

Sex: Female

Route of admini stration: gavage

Doses: 0, 10, 30 or 100 mg/kg

- bw/day

Exposure period: on gestation days 6 through 15

Frequency of treatment: Daily

Control group and treatment: a control was included (0 mg/kg

- bw/day)

Post

- observation period: Not stated

Statistical methods: Not statedDraft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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79 Method remarks: Female Sprauge

- Dawley rats (25/dose) were administered ADBAC (81.09%

a.i.) by gavage at doses of 0, 10, 30 and 100 mg/kg on gestation days 6 through 15 inclusive for

assessment of developmental toxicity.

RESULTS

NO AEL and LOAEL:

NOAEL (maternal) = 10 mg/kg/day

LOAEL (maternal) = 30 mg/kg/day based on clinical signs and decreased body weight gain

NOAEL (developmental) = 100 mg/kg/day

LOAEL (developmental) > 100 mg/kg/day

Remarks: There was no mortality observed a t any dose level. At 100 mg/kg/day, one dam

exhibited dehydration, unkempt appearance, loose feces and perioral wetness. At 30 mg/kg/day,

one dam was noted with perioral wetness, gasping, loose feces and urine strains. Decreased

body weight gain (12

- 13% ) was observed in maternal animals at 30 and 100 mg/kg/day during

gestation days 6

- 15. Food consumption was not consistently affected by treatment. There were

no treatment

- related increases in the incidence of fetal external, visceral, or skeletal

abnorm alities at any dose level.

CONCLUSIONS

Based on the results of this study, the Maternal NOAEL is 10 mg/kg/day, and the Maternal

LOAEL is 30 mg/kg/day, based on clinical signs and decreased body weight gain. The

Developmental toxicity NOAEL is 100 mg/k g/day, and the Developmental toxicity LOAEL >

100 mg/kg/day. There was no evidence for developmental toxicity of ADBAC in this study.

RELIABILITY CODE

2

REFERENCES

42351501 (MRID) Neeper

- Bradley, T. (1992) Developmental Toxicity Evaluation II of Alky l

Dimethyl Benzyl Ammonium Chloride (ADBAC) Administered by Gavage to CD Rats: Lab

Project Number: 91N0031. Unpublished study prepared by Union Carbide Chemicals and

Plastics Co., Inc. Bushy Run Research Center. 281 p.

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80 Study 2. Developmental toxicity gavage study of ADBAC in rabbits

Title: Developmental Toxicity Evaluation of Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) Administered by Gavage to New Zealand White Rabbits: Lab Project Number:

91N0032

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09%

METHOD

Method/guideline followed: Not stated

GLP: Not stated

Year study was performed: Not stated

Species/strain: New Zealand White rab bits

Sex: female

Route of administration: gavage

Doses: 0, 1, 3 or 9 mg/kg/day

Exposure period: on gestation days 6 through 18

Frequency of treatment: daily

Control group and treatment: 0 mg/kg/day

Post

- observation period: Not stated

Statistical m ethods: Not stated

Method remarks: In a developmental toxicity study in rabbits, ADBAC (81.09%) was

administered at doses of 0, 1, 3 and 9 mg/kg/day to pregnant New Zealand White rabbits

(16/dose) by oral gavage on gestation days 6 through 18.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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81 RESULTS

NOAEL and LOAEL:

NOAEL (maternal) = 3 mg/kg/day

LOAEL (maternal) = 9 mg/kg/day based on clinical signs of toxicity

NOAEL (developmental) = 9 mg/kg/day

LOAEL (developmental) > 9 mg/kg/day

Remarks: There was no mortality or abortions at any dose level. Hypoactivity and labored

breathing were observed at 9 mg/kg/day in 2 of 15 rabbits. There were no effects on maternal

body weight, food consumption, cesarean section observations or necropsy observations. In

offspring, there was no evidence of developm ental toxicity at any dose level tested.

CONCLUSIONS

The maternal NOAEL is 3 mg/kg/day, and the Developmental NOAEL is 9 mg/kg/day. The

Maternal LOAEL is 9 mg/kg/day, based on clinical signs of toxicity, and the Developmental

LOAEL is > 9 mg/kg/day. There was no evidence of developmental toxicity of ADBAC in this

study.

RELIABILITY CODE

2

REFERENCES

42392801 (MRID) Neeper

- Bradley, T.; Kubena, M. (1992) Developmental Toxicity Evaluation

of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Administere d by Gavage to New

Zealand White Rabbits: Lab Project Number: 91N0032. Unpublished study prepared by Union

Carbide. 179 p.

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82 Study 3. Developmental toxicity gavage range

- finding study of ADBAC in rabbits

Title: Devel opmental Toxicity Dose Range

- Finding Study of ADBAC Administered by Gavage

to New Zealand White Rabbits: Lab Project Number: 54

- 603

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09 % pure

METHOD

Method/guideline followed: 870.3700

GLP: Not stated

Year study was performed: Not stated

Species/strain: New Zealand White rabbits

Sex: female

Route of administration: gavage

Doses: 0, 1, 3, 10, 30 or 60 mg/kg/day

Exposure period : gestation days 6 through 18

Frequency of treatment: daily

Control group and treatment: 0 mg/kg/day

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a dose range

- finding study for developmental toxicity in rabb its, ADBAC

(81.09%) was administered at doses of 0, 1, 3, 10, 30 or 60 mg/kg/day to pregnant New Zealand

White rabbits (5/dose) by oral gavage on gestation days 6 through 18.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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83 RESULTS

NOAEL and LOAEL:

NOAEL (maternal) = 3 mg/kg/day

LOAEL (maternal) = 10 mg/kg/day

, based on clinical signs and reduced body weight gain and

food consumption

LOAEL (developmental) not established.

Remarks: Mortality was observed at doses of 30 and 60 mg/kg/day (2 and 5 doses,

respectively). Audible respiration was observed at doses greater than or equal to 10 mg/kg/day.

At doses greater than or equal to 30 mg/kg/day, clinical signs included hypoactivity, perioral

wetness, and labored breathing. At 60 mg/kg/day, clinical signs included paralysis, cold

extremities, prostrat ion, slow respiration, emaciation, loose feces, and perioral encrustation.

Decreased body weight gain and food consumption were observed at doses greater than or equal

to 10 mg/kg/day. Developmental toxicity was not observed at any of the doses tested.

CONCLUSIONS

The maternal NOAEL for the range

- finding study is 3 mg/kg/day and the LOAEL is 10

mg/kg/day, based on clinical signs and reduced body weight gain and food consumption. There

was no evidence of developmental toxicity of ADBAC in this study.

RELIABILITY CODE

2

REFERENCES

42734401 (MRID) Chun, J.; Neeper

- Bradley, T. (1993) Developmental Toxicity Dose Range

Finding Study of ADBAC Administered by Gavage to New Zealand White Rabbits: Lab Project

Number: 54

- 603. Unpublished study prepared by Union Carbide. 118 p.

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84 Study 4. Developmental toxicity gavage range

- finding study of ADBAC in rats

Title: Developmental Toxicity Dose Range

- Finding Study of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) Administered by Gavage to CD Rats: Lab Project Number: 54

-

613

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: ADBAC

Remarks: 81.09% pure

METHOD

Method/guideline followed: 870.3700

GLP: Not stated

Year study was performed: Not stated

Species/strain: CD rats

Sex: female

Route of administration: gavage

Doses: 0, 25, 50, 100, 200 or 400 mg/kg/day

Exposure period: gestation days 6 through 15

Frequency of treatment: daily

Control group and treatment: 0 mg/k g/day

Post

- observation period: Not stated

Statistical methods: Not stated

Method remarks: In a dose range

- finding study for developmental toxicity in rats, ADBAC

(81.09%) was administered at doses of 0, 25, 50, 100, 200 or 400 mg/kg/day to CD rats (5/ dose)

by oral gavage on gestation days 6 through 15, inclusive.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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85 RESULTS

NOAEL and LOAEL:

NOAEL (maternal) = 50 mg/kg/day

LOAEL (maternal) = 100 mg/kg/day , based on significantly increased incidence of perioral

wetness

NOAEL (developmental) = 100 mg /kg/day

LOAEL (developmental) = 200 mg/kg/day

, based on no survival

Remarks: Doses ≥ 200 mg/kg/day resulted in 100% mortality; necropsy findings revealed a

distended and change in color of the stomach, and distended intestines filled with mucoid fluid.

T hese dams also exhibited clinical signs including loose feces, perioral wetness and perioral

encrustation, ataxia, hypoactivity, urogenital area wetness and audible respiration. Maternal

toxicity observed at 100 mg/kg/day was manifest as significantly inc reased incidence of perioral

wetness.

CONCLUSIONS

The maternal NOAEL and LOAEL are 50 and 100 mg/kg/day, respectively. The NOAEL for

developmental toxicity is 100 mg/kg based on no survival of dams at 200 and 400 mg/kg/day.

RELIABILITY CODE

2

REFER ENCES

42645101 (MRID) Chun, J.; Fisher, L. (1993) Developmental Toxicity Dose Range

- Finding

Study of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) Administered by Gavage to

CD Rats: Lab Project Number: 54

- 613. Unpublished study prepared by Bushy Run Research

Center (BRRC). 104 p.

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86 B

- 14. PHARMACOKINETIC STUDIES

Study 1. Absorption, distribution, metabolism and excretion studies of ADBAC in rats

Title: Absorption, Distribution, Metabolism and Excretion Studies of Alkyl Dimethyl Benzyl

Ammonium Chloride (ADBAC) in the Rat

TEST SUBSTANCE

Identity: ADBAC

Remarks: purity 30%

METHOD

Method/guideline followed: 870.7485

Test type: in vivo

Species/strain/cell type or line: Sprague

- Dawley rats

Sex: Both

Age and body weight range of animals used: Not stated

Number of animals/sex/dose: not stated

Route of administration: Oral or intravenous

Vehicle: Not stated

Doses:

Group 1: single dose 10 mg/kg (oral or intravenous)

Group 2: 100 ppm ADBAC in diet f or 14 days

Group 3: single oral dose of 50 mg/kg

Excretion routes, body fluids, and tissues monitored and/or sampled during study: urine,

feces, unspecified tissues

Statistical methods used: Not stated

Method remarks: Disposition of ADBAC was examined in male and female Sprague

- Dawley

rats following a 10 mg/kg single dose by the oral or intravenous route, following exposure to 100

ppm ADBAC for 14 days in the diet, or after a single oral dose of 50 mg/kg. Ring

- labeled test

material was used.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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87 RESULTS

D etailed results:

Following oral administration, from 5

- 8% of the administered dose was eliminated in urine and

90

- 98% in feces. No apparent differences in disposition were noted between sexes. Following

intravenous administration, males eliminated 31% of the dose in urine and 44% in feces, while

females eliminated 21% in urine and 55% in feces following intravenous administration. After

oral administration, from 0.03%

- 0.58% of the administered dose was accounted for in tissues.

After intravenous adm inistration, tissue residues accounted for 33

- 36% of the dose and were

observed mainly in the carcass. The results of this study indicate that a majority of an

administered dose of ADBAC is eliminated in feces and involves biliary excretion.

Metabolites measured: Not stated

CONCLUSIONS

The results of this study indicate that a majority of an administered dose of ADBAC is

eliminated in feces and involves biliary excretion.

REFERENCES

40990701 (MRID) Selim, S. (1 989) Absorption, Distribution, Metaboli sm and Excretion Studies

of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in the Rat: BTC Study No. P01 359.

Unpublished study prepared by Biological Test Center. 247 p.

Supplements:

41087701 (MRID) Lin, P.; Selim, S. (1989) Addendum to Report Entitled "Absorption,

Distribution, Metabolism and Excretion Studies of Alkyl Dimethyl Benzyl Ammonium Chloride

(ADBAC) in the Rat" MRID 40990701 : Study No. PO1 359. Unpublished study prepared by

Biological Test Center. 44 p.

and

44783401 (MRID) Mazur, P. (1 99 9) Absorption, Distribution, Metabolism and Excretion

(ADME) Studies of Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) in the Rat and

Addendum: Lab Project Number: P01359. Unpublished study prepared by ADBAC Quat Joint

VentureIChemical Specialities Manufa cturers Assoc. 4 p.Draft HPV4 Chemical Data Adequa cy Review CAS No. 61789

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88 CAS No. 61789

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- 9: Summary of Endpoints

Endpoint Study Information

Provided Acceptable Data Gap

Aquatic Effects

Acute Toxicity to Fish Yes Yes No

Acute Toxicity to Daphnia Yes Yes No

Toxicity to Aquatic Plants Yes Yes No

Hea lth Effects

Acute Toxicity Yes Yes No

Repeated

- Dose Toxicity Yes Yes No

Genetic Mutation Yes Yes No

Chromosomal Aberrations Yes Yes No

Toxicity to Reproduction Yes Yes No

Developmental Toxicity Yes Yes No