A Compilation of Two Decades of Mutagenicity ... - ACS Publications

Chem. Res. Toxicol. 2006, 19, 627-644

627

Chemical Profiles A Compilation of Two Decades of Mutagenicity Test Results with the Ames Salmonella typhimurium and L5178Y Mouse Lymphoma Cell Mutation Assays† H. E. Seifried,*,‡ R. M. Seifried,§ J. J. Clarke,| T. B. Junghans,⊥ and R. H. C. San| DiVision of Cancer PreVention, National Cancer Institute, National Institutes of Health, RockVille, Maryland 20852, Dwight D. Eisenhower Army Medical Center, Fort Gordon, Georgia 30905, BioReliance, InVitrogen Corporation, RockVille, Maryland 20850, and Technical Resources International Inc., Bethesda, Maryland 20817 ReceiVed December 21, 2005

As previously reported [Cameron, T. P., Rogers-Back, A. M., Lawlor, T. E., Harbell, J. W., Seifried, H. E., and Dunkel, V. C. (1991) Gentoxicity of multifunctional acrylates in the Salmonella/mammalianmicrosome assay and mouse lymphoma TK+/- assay. EnViron. Mol. Mutagen. 17, 264-271], the National Cancer Institute (NCI) shares the responsibility of selecting the most significant chemicals for carcinogenicity testing by the National Toxicology Program (NTP) and has used data from Salmonella and mouse lymphoma mutagenicity assays to aid in the selection and prioritization of chemicals to be further evaluated in chronic 2 year rodent studies. In addition, a number of antineoplastic and anti-AIDS drugs in preclinical evaluation were tested for the NCI’s Division of Cancer Treatment Toxicology Branch. In the NCI/NTP chemical selection process, it is no longer necessary to test chemicals prior to sending them to the NTP so the NCI program has ceased performing mutagenicity tests. Some of the testing data has been made available in summary form in the Chemical Carcinogenisis Research Information System (CCRIS), which is searchable on the NLM TOXNET system. The limitations in using this source are that only summary results are available and many negative test results are not included. A summary table that presents the results for each compound is provided in the Appendix with raw data provided in the Supporting Information. The Appendix table contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay. Introduction In the past, we would prepare manuscripts giving complete test data following the NCI’s practice of grouping compounds according to usage (e.g., dyes, pesticides, adhesives, monomers) or structural similarities (e.g., acrylates, naphthenates, oximes, thiazoles) as this provided the most efficient nomination process. The number of compounds initially considered in the grouping or class was then substantially reduced by considering the available in vitro as well as animal test data, production, use and exposure estimates, structure-activity relationships, etc. These class studies have been carried out as part of the NCI chemical selection process since the early 1980s, and two dye class studies were published (1, 2). Since that time, several other class studies have been prepared (3-11), but after careful consideration of the time and effort involved in preparing individual research reports and after extensive discussions with the journal editorial staff, the decision was reached to publish a compendium of all test results in a readily searchable format as a journal supplement, making all †

This paper is dedicated to Paul E. Seifried in honor of his 90th birthday. * To whom correspondence should be addressed. ‡ National Institutes of Health. § Dwight D. Eisenhower Army Medical Center. | Invitrogen Corporation. ⊥ Technical Resources International.

of the data available for those wishing to carry out structural or other computer-based reanalysis of the data. This substantially expands the publicly available data of the summary reports of Haworth et al. (12), Dunkel et al. (13, 14), Mortelmans et al. (15), Myhr et al. (16), and Zeiger et al. (17-19) for the Ames test and Oberly et al. (20), McGregor et al. (21-24), and Mitchell et al. (25) for the mouse lymphoma test. Summary data for each compound are included in Table 1 of the Appendix including whether the studies were positive or negative, the Salmonella strain testing positive, the dose ranges tested, and the results of an extensive literature search, which are presented in the column titled references at the far right of the table, for other pertinent mutagenicity tests.

Materials and Methods Chemicals. The chemical names, Chemical Abstracts Service (CAS) numbers, and structure of each tested compound or product are listed in the Supporting Information (Table 2). The tested agents were acquired by NCI contractors [Illinois Institute of Technology Research Institute, Chicago, IL, and Midwest Research Institute (MRI), Kansas City, MO], analyzed for purity by MRI, and supplied as coded samples to the contract laboratory (BioReliance, Inc., Rockville, MD). The bulk materials were stored at -20 °C, 4 °C, or room temperature as required to maintain compound stability. Stock solutions of each chemical were prepared in the appropriate solvent immediately prior to use. In the Supporting Information, the solvents are listed in Tables 3 and 4; these tables also contain

10.1021/tx0503552 CCC: $33.50 © 2006 American Chemical Society Published on Web 04/20/2006

628 Chem. Res. Toxicol., Vol. 19, No. 5, 2006 complete data for the Ames test (Table 3) and the mouse lymphoma mutagenicity assay (Table 4). Salmonella/Mammalian-Microsome Mutagenicity Assay. The experimental materials, methods, and procedures as explained below are based on those described by Ames et al. (26). For initial mutagenicity testing, the plate incorporation assay was used; some compounds were also tested using the flavin mononucleotide (FMN)-dependent reducing conditions described by Prival and Mitchell (27) to break the diazo bonds of the condensed dyes, forming the individual constituents. Bacterial Strains. Salmonella typhimurium histidine auxotrophs TA98, TA100, TA1535, TA1537, and TA1538 were obtained from Dr. Bruce Ames, University of California (Berkeley, CA). Cultures were grown overnight in Oxoid nutrient broth no. 2 and were removed from incubation when they reached a density of (1-2) × 109 cells/mL. On the day of use, all tester strain cultures were checked for genetic integrity as recommended by Ames et al. (26). S9 Preparation. Liver S9 homogenate was prepared from male Sprague-Dawley rats and Syrian golden hamsters that had been injected with Aroclor 1254 at 500 mg/kg body weight. The postmitochondrial (microsomal) enzyme fractions were prepared as described by Ames et al. (26). The components of the S9 mix were 8 mM MgCl2, 33 mM KCl, 5 mM glucose-6-phosphate, 4 mM NADP, 100 mM sodium phosphate (pH 7.4), and the appropriate S9 homogenate at a concentration of 0.1 mL/mL of mix. For each plate receiving microsomal enzymes, 0.5 mL of S9 mix was added. Plate Incorporation Methodology. For testing in the absence of S9 mix, 100 µL of the tester strain and 50 µL of the solvent or test chemical were added to 2.5 mL of molten selective top agar at 45 ( 2 °C. When S9 was used, 0.5 mL of S9 mix, 50 µL of tester strain, and 50 µL of solvent or test chemical were added to 2.0 mL of molten selective top agar at 45 ( 2 °C. After it was vortexed, the mixture was overlaid onto the surface of 25 mL of minimal bottom agar. After the overlay had solidified, the plates were incubated for 48 h at 37 ( 2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. The doses that were tested in the mutagenicity assay were selected based on the levels of cytotoxicity observed in a preliminary dose range-finding study using strain TA100. Ten dose levels of the chemical, one plate per dose, were tested in both the presence and the absence of induced hamster S9. If no toxicity was observed, a total maximum dose of 10 mg of test chemical per plate was used. The criteria used to evaluate a test were as follows: for a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. If the study showed a dose response with a less than 3-fold increase on TA1537 or TA1538, the response had to be confirmed in a repeat experiment. Preincubation Methodology under Reductive Conditions. For tests using the FMN-modified assay (27), strains TA98 and TA100 were used. The bacteria, uninduced hamster liver S9 (30% v/v), cofactors (FMN, NADH, glucose-6-phosphate dehydrogenase, and glucose-6-phosphate), and test chemical were added, mixed, and incubated at 30 °C for 30 min without shaking. Nitrogen was blown over the preincubation tube to keep the atmosphere reduced. At the end of the incubation period, 2 mL of molten top agar (26) was added to each sample tube and the mixture was poured on a minimal agar plate containing 0.5% glucose rather than the 2% glucose specified by Ames et al. (26). The plates were then incubated at 37 °C for 48 h. The positive control in all FMN experiments was Congo red. All plates were counted with an Artek automated colony counter (Artek 880, DynaTech, Chantilly, VA) or Minicount colony counter (Imaging Products International, Inc., Chantilly, VA), which was calibrated prior to use.

Seifried et al. L5178Y TK+/- Mouse Lymphoma Mutagenicity Assay. L5178Y TK+/- 3.7.C mouse lymphoma cells were originally obtained from Dr. Donald Clive, Burroughs Wellcome Co. (Research Triangle Park, NC). The cells were grown in Fischer’s medium for leukemic cells of mice (Gibco, Grand Island, NY, or Quality Biological, Gaithersburg, MD) supplemented with 10% horse serum (Gibco or Hyclone, Logan, UT) and 0.02% pluronic F-68 (BASF Wyandotte Corp., Wyandotte, MI). Cells were screened for the presence of mycoplasma after cryopreservation. New cultures were initiated at approximately 3 month intervals from cells stored in liquid N2. The toxicity of each chemical was determined both with and without liver S9 prepared from Aroclor 1254-induced male Sprague-Dawley rats. S9 mix was prepared according to the procedure of Clive et al. (28). Cells at a concentration of 6 × 105/mL (6 × 106 cells total) were exposed for 4 h to a range of concentrations from 0.0005 to 10000 µg/mL. The cells were then washed, resuspended in growth medium, and incubated at 37 ( 1 °C for 48 h. The rate of cell growth was determined for each of the treated cultures and compared to the rate of growth of the solvent controls. The doses of chemical selected for testing were within the range yielding approximately 0-90% cytotoxicity. For each assay, there were 2-4 solvent controls, a positive control of ethyl methylsulfonate at 4.7 × 10-6 M (or methyl methanesulfonate at 10-20 µg/ mL) for the test without metabolic activation, and a positive control of 3-methylcholanthrene at 1.86 × 10-5 M (or dimethylbenz[a]anthracene at 0.5-4 µg/mL) for the test with metabolic activation. The mutagenicity assay was performed according to the procedure described by Clive and Spector (29). A total of 1.2 × 107 cells in duplicate cultures were exposed to the test chemical, positive control, and solvent control for 4 h at 37 ( 1 °C, washed twice with growth medium, and maintained at 37 ( 1 °C for 48 h in log-phase growth to allow recovery and mutant expression. Cells in the cultures were adjusted to 3 × 105/mL at 24 h intervals. They were then cloned (1 × 106 cells/plate for mutant selection and 200 cells/plate for viable count determinations) in soft agar medium containing Fischer’s medium, 20% horse serum, 2 mM sodium pyruvate, 0.02% pluronic F-68, and 0.23% granulated agar (BBL, Inc., Cockeysville, MD). Resistance to trifluorothymidine (TFT) was determined by adding TFT (final concentration, 3 µg/mL) to the cloning medium for mutant selection. The 100× stock solution of TFT in saline was stored at -70 °C and was thawed immediately before use. Plates were incubated at 37 ( 1 °C in 5% CO2 in air for 10-12 days and then counted with an Artek automated colony counter (Artek 982, DynaTech) or ProtoCol colony counter (Synbiosis, Frederick, MD). Only colonies larger than ∼0.2 mm in diameter were counted. Mutant frequencies were expressed as mutants per 106 surviving cells. Although there are several different methods for evaluating mouse lymphoma data, results from this study were interpreted using a doubling of the mutant frequency over the concurrent solvent-treated control value as an indication of a positive effect, together with evidence of a dose-related increase. Doubling of the mutant frequency was previously reported as representing a positive effect (28). Only doses yielding total growth values of 10% were used in the analysis of induced mutant frequency. Doses yielding less than 10% total growth were used in determining dose response. The size of mutant mouse lymphoma colonies was also determined using an Artek 982 colony counter/sizer or the ProtoCol colony counter. An internal discriminator was set to step sequentially to exclude increasingly larger colonies in approximate increments of 0.1 mm in colony diameter. The size range used was from ∼0.2 to 1.1 mm.

Results and Discussion The summary results of the tests in S. typhimurium are shown in Table 1 of the Appendix, and the complete data are shown in the Supporting Information. The lowest concentrations at which a positive increase in mutant frequency was achieved are also given in Table 1 for those tests eliciting a positive

Ames Salmonella and Mouse Lymphoma Cell Mutation Assays

Chem. Res. Toxicol., Vol. 19, No. 5, 2006 629 Table 1a

Ames Salmonella evaluation

mouse lymphoma evaluation nonactivated

chemical name

CAS no.

evaluation

dose (µg/plate)

abietic acid acenaphthenequinone

514-10-3 82-86-0

negative P/100

33-3333 3.3-10000

acesulfame K acetaldehyde

55589-62-3 75-07-0

negative negative

acetaldehyde oxime

107-29-9

negative

acetamide, 2-[[[(2-chloro ethyl) nitrosoamino] carbonyl]methylamino] acetic anhydride 4-acetyl-4-phenylpiperidine 2-acetylpyridine acetyl tributyl citrate acrylonitrile acrylonitrile

81965-43-7

P/33

108-24-7 34798-80-6

negative negative

1122-62-9 77-90-7 107-13-1 107-13-1

strain

old eval/ LED

S9-activated

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

P/46 P/30

P/46 equivocal

N P/20

N equivocal

667-10000 100-10000

N P/0.07

N P/0.07

N P/0.4

N I

974-2000 0.07-0.8

100-10000

P/15

N

P/0.23

I

0.1-22

P/1.0

P/1.0

P/0.25

P/0.25

0.1-5.0

8-5000 100-10000

P* N

I N

N N

I I

0.04-0.3 201-3715

negative negative negative positive

100-10000 333-10000 333-10000 100-6667

P/4000 N

P/4000 I

WP/4000 N

I N

1000-4500 10-480

P/0.054

P/0.073

P/0.034

P/0.034

0.034-0.15

124-04-9 315-30-0 107-18-6 762-72-1 2835-68-9 130194-90-0

negative negative negative negative negative negative

667-10000 667-10000 1-1000 1-1000 100-10000 100-5000

N N P/5.4 N E P/0.01

N N P/7.3 N N P/0.01

N N N N E P/0.05

N N N N N P/0.05

718-2000 97-200 0.002-11 0.01-0.37 300-500 0.005-1.0

2835-97-4 2835-98-5 2977-71-1 2835-99-6 2835-95-2 2835-98-5 56-05-3

negative negative negative negative negative P/1000 negative

100-10000 100-10000 10-10000 3.3-3333 100-10000 33-3333 100-10000

P/50 P/2 P/3 P/4 P/25 P/10 P/700

P/50 P*/3 P/3 E P/50 P/15 P/700

P/100 P/20 P/35 N N P/200 WP/250

E P/20 P/50 I N E* I

25-250 1.0-30 1.0-100 2.0-500 25-1500 5.0-300 50-1000

2349-67-9

negative

100-10000

P/500

P/500

E

N

500-5000

6285-57-0

P/1

0.01-500

N

N

N

N

8-44

3-aminoproprionitrile 4-aminostyrene

151-18-8 1520-21-4

negative P/333

100-10000 33-3333

N

I

N

N

500-4000

4-amino-m-toluenesulfonic acid 6-amino-m-toluenesulfonic acid n-amyl-nitrite

98-33-9

negative

10-10000

N

N

P/3500

P/3500

3500-7500

88-44-8

negative

10-10000

N

N

N

E

1642-3680

463-04-7

P/3333

100-10000

N

I

N

N

0.11-0.36

n-amyl nitrite trans-anethole p-anisaldehyde

463-04-7 4180-23-8 123-11-5

negative negative

1-10000 33-6667

N N N

N N N

N P/15 P/0.2

N E P/0.2

0.04-0.44 1-80 0.09-0.9

anthranilic acid

118-92-3

negative

333-10000

N

N

P/5000

P/6000

1000-8000

9,10-anthraquinone

84-65-1

negative

50-5000

adipic acid allopurinol allyl alcohol allyltrimethylsilane 4-aminobenzamide 9-aminocamptothecin (R,S) 2-amino-m-cresol 2-amino-p-cresol 2-amino-p-cresol HCl 4-amino-m-cresol 5-amino-o-cresol 6-amino-m-cresol 2-amino-4,6-dichloropyrimidine 5-amino-2-mercapto1,3,4- thiadiazole 2-amino-6-nitrobenzothiazole

1-50

TA98, 100

TA100

TA1535

TA100

TA98, 100, 1537, 1538

20-149 10-60

refs 182

2, 32, 57, 183 204, 206, 219

102 4, 12, 19, 47, 108, 115, 121, 122, 124, 125, 134, 156, 167, 172,188, 216, 260, 295 207, 240 283 137

293

TA98, 100, 1535

TA98, 1535

63, 209

93, 266 73, 108, 115, 167, 282 81, 158, 159, 169, 293 20, 25, 127, 274, 293

630 Chem. Res. Toxicol., Vol. 19, No. 5, 2006

Seifried et al. Table 1. Continued



chemical name

CAS no.

evaluation

dose (µg/plate)

antimony(III) chloride antimony(V) chloride

10025-91-9 7647-18-9

negative P/100

100-5000 33-667

antimony potassium tartrate antimony(III) sulfide antimony(V) sulfide

28300-74-5

negative

100-10000

1345-04-6 1315-04-4

negative negative

100-10000 10-10000

5-azacytidine azacytosine arabinoside azidothymidine (AZT) azodicarbonamide 2,2′-azodiisobutyronitrile B69 barium lithol (D&C red no. 12) Barton rhodium complex bathophenanthroline Baygon (2-isopropoxyphenyl- N-methylcarbamate) benzil (dibenzoyl) O(6)-benzylguanine [6-(phenyl methoxy)1H-purin-2-amine] benzylideneacetone (methyl styryl ketone) benzonitrile benzophenone benzothiazole 2-benzoxazolinone bilberry extract (myrtocyan) Biobor JF (2,2′-(1methyltrimethylenedioxy)-bis(4-methyl1,3,2-dioxaborinane) biochanin A bismaleimide bisphenol S bis (trichloromethyl) sulfone bixin

320-67-2 65886-71-7 30516-87-1 123-77-3 78-67-1

P/0.3 negative negative P/333 negative

0.1-100 10-10000 0.1-50 100-6667 100-10000

negative

strain

old eval/ LED

new eval/ LED

S9-activated old eval/ LED

new eval/ LED

dose (µg/mL)

TA98, 100 P/11

TA1535

P/15

P/45

P/45

11-60

P/0.1

P/0.1

P/7

I

0.1-12

E N E N N

N I N N I

P/2000 N E N N

E N N N N

400-4000 73-300 600-1000 8.0-5000 170-402

0.3-333

N

I

N

N*

6-265

negative

100-10000

P/1000 P/173

P/1500 P/173

P/150 P/462

E P/462

134-81-6 19916-73-5

negative

100-10000

N P/200

I P/300

P/50 WP/300

N I

10-3000 50-500

122-57-6

P/100

P/20

P/50

WP/60

N

10-60

100-47-0 119-61-9 95-16-9 95-16-4 84082-34-8

negative negative negative negative

N N N P/1000

N N N E

N N N N

N N N N

0.39-1.21 35-170 10-250 50-1100

N

I

N

N

0.9-20

P/40 N

I N

P/5.0 P/30

P/7.5 E

0.5-40 0.19-30

P/250

P/300

N

N

100-300

N

N

N

N

0.04-15

N

N

P/225

P/250

10-300

N N

N N

P/100 P/20

E I

7.3-15 10-300 0.1-20

N P/107

N P/107

P/200 P/68

P/200 P/92

25-500 19-163

N N P/60 WP/74 N

I N E N N

N N N P/114 N

I N N E N

.001-.1 0.07-6.1 20-210 36-438 3-10

P/1.3 P/3.6 P/40

P/2.1 P/5.5 P/40

N N N

N N N

0.08-3 1.7-7.5 10-300

TA100

1103-38-4

1662-01-7 114-26-1

10-333

TA100

10-2000 100-10000 33-10000 100-10000

2665-13-6, 8063-89-6

491-80-5 13676-54-5 80-09-1 3064-70-8

negative negative negative

6983-79-5

P/333

100-10000

black cohosh (Cimicifuga racemosa) blue green algae (Cell Tech) borane-THF copmplex brefeldin A prodrug 2-bromoacetophenone 2-bromobutane 1-bromo-3-chloropropane 2-bromo-4,6-dintroaniline

84776-26-1

negative

100-10000

negative

100-10000

20350-15-6 70-11-1 78-76-2 109-70-6 1817-73-8

negative E negative P/1000 P/10

100-1000 0.1-33 100-10000 100-10000 10-1000

1-bromo-4-fluorobenzene β-bromo-β-nitrostyrene N-bromosuccinimide bromoxynil 1,3-butadiene

460-00-4 7166-19-0 128-08-5 1689-84-5 106-99-0

negative P/3333 negative negative

0.33-33 33-10000 100-10000 0.1-10

butanal oxime 2-butanone oxime butyl acrylate

110-69-0 96-29-7 141-32-2

negative negative

100-10000 100-10000

refs 128

3.3-1000 1.0-1000 0.1-3333

TA98, 100

TA100 TA98, 100, 1537, 1538

TA100

150-5000 75-1744

4, 84, 106, 158 122, 232

17

293 121, 169 35, 103

13, 258

10 245 130 119, 294

5, 6, 48, 122, 141, 152 219 219 280, 294


Chem. Res. Toxicol., Vol. 19, No. 5, 2006 631

Table 1. Continued Ames Salmonella evaluation


chemical name

CAS no.

evaluation

dose (mg/plate)

t-butyl chloride n-butyl nitrite

507-20-0 544-16-1

P/1000

100-10000

sec-butyl nitrite caffeic acid

924-43-6 331-39-5

negative negative

(-)-calanolide B calcium naphthenate camphor quinone capsaicin

142632-33-5 61789-36-4 10373-78-1 404-86-4

carbonyl iron carbovir carbovir carmethizole (hydrochloride) carminic acid

7439-89-6 118353-05-2 118353-05-2 123298-15-7

old eval/ LED

strain

new eval/ LED


new eval/ LED

dose (µg/mL)

refs

N P/0.22

N P/0.39

N E

N P/0.74

1500-5000 0.16-0.87

100-10000 100-10000

P/0.25 P/307

P/0.25 P/307

P/0.9 E

P/0.9 N

0.04-1.4 114-900


75-5000 100-10000 100-10000 10-10000

N P/0.005 P/200

N P/0.005 P/600

N N N

N N N

negative

100-10000

negative P/333

40-5000 33-2000

P/4500 N N P/9

N N I P/9

P/1000 N P/1500 P/12

E N P/1500 P/12

500-5000 234-500 441-5000 9-25

1260-17-9

negative

12-10000

P/907

P/408

P/1935

P/1935

408-4000

trans-(β)-caryophyllene cedarwood oil cedrene cedrol chavicol n-(3-chloroallyl)hexaminium chloride (quaternium 15) 4-chloro-6-amino-mtoluene sulfonic acid 4-chloroaniline

87-44-5 8000-27-9 469-61-4 77-53-2 501-92-8 4080-31-3


100-10000 100-10000 33-10000 2.5-10000

P/25

N

E

E

negative

6-800

N P/3.6

N P/3.6

N P/23

N P/36

88-51-7

P/3333

667-10000

TA98

N

N

N

E

288-600

106-47-8

P/333

33-10000

TA98

P/300

E

P/100

I

30-300

p-chlorobenzaldehyde 2-chlorobutane chlorogenic acid chloromethyldimethyl vinyl silane 1-chloro-2-methylpropane (isoamyl chloride) 1,2-bis(2-chlorophenyl)1,2-diphenylethane 2-chlorotoluene (o-chlorotoluene) p-chloro-R,R,R-trifluorotoluene chlorotrimethylsilane chlorsulfaquinoxaline cholesterol 5-R,6R-epoxide cholestyramine chromium(III) chloride hexahydrate chromium hexacarbonyl chromium picolinate C.I. acid blue 9

104-88-1 78-86-4 327-97-9 16709-86-7


10-1000 100-10000 333-10000 10-10000

P/179 N N N

N N N I

N N P/6545 N

N N P/6545 N

107-84-6

negative

33-10000

7146-88-5

negative

3.3-10000

N

N

P/350

E

50-350

95-49-8

negative

10-1200

N

N

N

N

50-175

98-56-6

negative

8-800

N

N

N

E

0.01-0.07

148

75-77-4 97919-22-7 1250-95-9


100-10000 33-5000 100-10000

WP/0.035 P/2179 P/3071

N N E

N N N

N N I

0.02-0.12 173-2500 63-5000

110

11041-12-6 10060-12-5

negative P/10000

100-10000 100-10000

N P/725

I N

N P/1900

N E

114-500 500-2000

13007-92-6 10060-12-5 2650-18-2

negative negative P/3333

100-10000 100-10000 333-10000

N P/100 N

N P/300 N

P/119 P/100 P/571

P/247 P/500 P/571

119-333 25-500 100-2179

C.I. acid blue 74

860-22-0

negative

100-10000

N

N

P/92

P/92

92-2000

C.I. acid green 5

5141-20-8

P/1000

333-10000

P/553

P/669

N

N

206-6000

C.I. acid orange 10

1936-15-8

negative

333-10000

N

N

P/2923

E

602-10000

TA100, 1535

TA98, 100

TA102

TA98, 1538

TA98, 158

5.1-75 0.005-0.5 200-800

63, 194 63, 209 61, 78, 117, 122, 271

95 9, 31, 80, 122, 171, 267

20, 139, 225

15-140

0.00065-0.14 3.6-100

50-614 500-5000 500-10000 0.054-0.2

293

121, 122, 159, 169, 197, 212, 270, 282 57, 192 78, 106

288

288 8, 121, 159 22, 26, 106, 121, 159, 195 121, 122, 159 26, 122, 152, 159, 293





chemical name

CAS no.

evaluation

dose (µg/plate)

strain

old eval/ LED

S9-activated

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

C.I. acid red 14 (carmoisine) C.I. acid red 18 (SX purple) C.I. acid red 26 (Ponceau MX)

3567-69-9

negative

333-10000

N

N

N

N

685-5000

2611-82-7

negative

333-10000

N

N

N

I

500-10000

3761-53-3

P/1000

333-10000

TA100

N

N

P/10000

E

2288-10000

C.I. acid red 51 (erythrosine sodium; 2′,4′,5′,7′-tetraiodofluorescein, disodium salt) C.I. acid red 51 C.I. acid red 52 C.I. acid red 52 C.I. acid violet 49

16423-68-0

P/333

333-10000

TA102

P/100

P/120

P/120

P/120

60-200

16423-68-0 3520-42-1

P/179

P/179

P/6667

667-10000

TA98

1694-09-3

P/333

3-333

TA98

P/310 N I N

50-369 250-3000 500-5000 3-601

C.I. acid yellow 23

1934-21-0

negative

333-10000

C.I. acid yellow 151 C.I. basic blue 3 [7-(N,N-diethylamino)phenoxazine-3-N,Ndiethyliminium chloride] C.I. basic red 18

12715-61-6 33203-82-6

negative P/67

333-10000 10-1000

14-97-03-1

P/1

1.0-100

C.I. basic red 29 [3-methyl-2-((1-methyl2-phenyl-1H-indol-3-yl) azo)thiazoliumchloride] C.I. basic violet 4 (ethyl crystal violet) C.I. brilliant black BN (food black 1)

42373-04-6

P/333

100-6666

2390-59-2

negative

2519-30-4

C.I. direct black 22

6473-13-8

negative hamster reductive assay P/3.3

100-10000

C.I. direct black 22

6473-13-8

P/3.3

1.0-10000

C.I. direct blue 6

2602-46-2

P/1

1.0-10000

C.I. direct blue 14 (trypan blue)

72-57-1

P/1 hamster reductive assay

1.0-10000

C.I. direct blue 53

314-13-6

P/100

1.0-10000

C.I. direct red 2 (benzopurpurine 4B) batch A C.I. direct red 2 (benzopurpurine 4B) batch B C.I. direct red 80 C.I. direct yellow 4 C.I. disperse brown 1

992-59-6

negative

992-59-6

C.I. disperse red 60 (1-amino-4-hydroxy-2phenoxyanthraquinone)

refs 26, 121, 122, 159 26, 159 121, 122, 159, 205, 292, 296 26, 121, 122, 131, 138, 159, 195, 225

P/88

P/173

P/310 N P/3000 N

N

N

N

N

N P/12

N P/23

N P/6.6

N P/12

179-971 1-23

N

N

P/36

P/36

6-65

274

P/5

I

P/217

I

2.5-289

27

0.3-100

N

N

N

I

10-10000

N

N

P/470

E

TA98

TA98, 1535, 1538 TA1537

TA98, 100, 1537, 1538 TA98, 100 TA98, 100 TA98, 100

4857-10000

289 22, 121, 122, 159, 217, 264, 292 22, 26, 106, 121, 122, 159, 205, 210, 263

0.001-6 470-3922

26, 159, 205, 296

N

N

N

E

1000-10000

N

N

N

N

3069-5000

P/4144

E

E

N

1001-5800

10-10000

N

N

N

N

600-1000

126, 214, 294

negative

10-10000

N

N

N

N

500-3075

126, 214, 294

2610-10-8 91-34-9 23355-64-8


333-10000 333-10000 1.0-10000

N N P/111

N N P/111

N N P/46

N N N*

2429-5000 101-1461 20-150

17418-58-5

P/333

333-10000

P/520

N

N

N

TA98, 100, 1538

TA98, 100, 1537, 1538 TA98

1-1000

159, 205, 214, 296 45, 99, 114, 121, 159, 205, 214 159, 205

159





evaluation

dose (µg/plate)

2832-40-8

P/1

1.0-10000

16090-02-1

negative

10-1000

2519-30-4 2353-45-9

negative

333-10000

C.I. food red 1 (Ponceau SX)

4548-53-2

negative

1000-10000

C.I. food red 6 (Ponceau 3R)

3564-09-8

P/1000

333-10000

trans-cinnamaldehyde (3-phenyl-2-propenal)

104-55-2

negative

100-10000

trans-cinnamic acid [(E)-3-phenyl-2propenoic acid] cinnamyl alcohol (3-phenyl-2propen-1-ol) cinnamyl alcohol cinnamyl anthranilate (3-phenyl-2-propenoic acid, 3-phenyl-2-propenyl ester) cinnamyl cinnamate (3-phenyl-2-propenyl-1-ol, 2-amino-benzoate) C.I. pigment yellow 74 C.I. solvent orange 7 (Sudan red) C.I. solvent yellow 3 (2-amino-5-azotoluene)

140-10-3

negative

10-1000

chemical name

CAS no.

C.I. disperse yellow 3

C.I. fluorescent brightener FW-1 C.I. food black 1 C.I. food green 3

C.I. solvent yellow 5 (food yellow 10; 1-phenylazo2-naphthylamine) C.I. solvent yellow 14 (Sudan I; 1-phenylazo2-naphthol) C.I. vat yellow 2 (2,8-diphenylanthra(2,1-D:6,5-d′) bisthiazole-6,12-dione) cobalt naphthenate colchicine copper naphthenate coumestrol (3,9-dihydroxy6H-benzofuro(3,2-c)(1)benzopyran-6-one) CPEC (cyclopentenyl cytosine) cromolyn sodium curcumin

strain TA98, 100, 1537, 1538

TA98, 100

104-54-1

old eval/ LED

new eval/ LED


new eval/ LED

dose (µg/mL)

refs

N

N*

N

I

7-487

26, 122, 159, 293

N

N

N

N

200-1000

121, 150

N P/4435

N N

P/470 N

E N

470-3922 1304-10000

N

N

N

N

3571-10000

P/3139

E

N

E

400-6000

P/0.005

P/0.005

P/0.036

P/0.049

P/500

E

P/1800

N

200-2000

P/200

I

P/214

P/291

137-714

0.001-0.049

183, 235

104-54-1 87-29-6

negative negative

33-333 1.0-1000

N N

N N

N P/17

N E

122-69-0

negative

333-10000

P/0.046

I

P/0.25

P/0.34

0.02-0.7

65

6358-31-2 3118-97-6

P/33

1.0-1000

N N

N N

N N

N N

972-2000 1-349

97-56-3

P/10

1-666

N

N

P/19

P/30

4.5-40

P/12

E

N

N

26, 293 82, 101, 121 26, 34, 113, 121, 122, 133, 149, 160, 164, 193, 217, 244 22, 121

P/44

N

P/5.5

P/5.5

N N

N N

P/0.17 N

E N

0.01-0.22 0.01-0.1

P/0.061

P/0.049

P/0.049

0.01-0.1

TA98, 1538 TA98, 100, 1538

85-84-7

3-18 3-22

22, 121, 122, 159 22, 26, 121, 122, 159, 210 22, 26, 121, 122, 159, 205 9, 50, 57, 137, 252 66, 137, 183

1-19

842-07-9

negative

333-10000

129-09-9

negative

667-10000

61789-51-3 64-86-8

P/2000 negative

100-10000 100-10000

1338-02-9 479-13-0

negative negative

33-1000 33-10000

P/0.049

115224-32-3

negative

40-5000

P/0.09

P/0.09

P/0.31

P/0.37

0.04-0.5

15826-37-1 458-37-7

negative negative

333-10000 0.3-10000

N

N

N

N

4857-10000

TA98

0.9-350

106, 183, 293

101, 122, 153, 293

23, 104, 105 13, 258

106, 170





chemical name

CAS no.

evaluation

dose (µg/plate)

old eval/ LED

strain

new eval/ LED


new eval/ LED

dose (µg/mL)

7-cyano-5,7,8,9,10,11,11a,12-octahydro-5(hydroxymethyl)-4methoxy-13-methyl8,11-iminoazepino(1,2-b)-isoquinoline10-carboxylic acid cyclohexanone

96251-59-1

negative

0.75-50

P/0.05

P/0.1

P/0.1

P/0.1

0.05-0.5

108-94-1

negative

667-10000

N

N

P/1.4

P/2.6

0.1-7.5

cyclohexanone oxime cyclohexene oxide

100-64-1 286-20-4

negative negative

100-8000 333-10000

P/1938 P/600

P/2485 P/600

N P/100

N P/150

1434-4000 100-1200

L-cysteine

52-90-4

P/333

333-10000

P/46

P/75

P/3238

P/3238

36-6666

daidzein (4',7-dihydroxyisoflavone) dazomet trans,trans-2,4decadienal decahydronaphthalene (decalin) deferiprone deferoxamine attached to high molecular starch deferoxamine mesylate dexrazoxane [(+)- 4,4′propylenedi-2,6piperazinedione] dexrazoxane dextran diaminomaleonitrile 1,8-diazabicyclo[5.4.0]undec-7-ene dibenzofuran dibenzosuberone (10,11-dihydro-5Hdibenzo(a,d)cyclohepten-5-one) 5,6-dichloro-2-benzothiazolamine cis-1,4-dichloro-2-butene

486-66-8

negative

100-10000

533-74-4 25152-84-5

negative negative

3.3-1000 0.33-10000

N

N

N

N

0.5-90

91-17-8

negative

100-10000

N

N

N

N

P/10 N

P/50 N

P/25 N

E N

trans-1,4-dichloro2-butene dichloromethylvinyl silane 1,4-dichlorophthalazine 2,3-dichloropropylene

2,3-dichloroquinoxaline dideoxyadenosine 2,3-dideoxycytidine dideoxyinosine 1,1-diethoxymethane (ethoxymethyl ethyl ether) diethyl hydroxypyridinone (CP94) 7,8-dihydro-(-)calanolide B 3,4-dihydroxy-3cyclobutene-1,2-dione diisopropylcarbodiimide (N,N′-methanetetraylbis2-propanamine)

TA100

100, 122, 151 6, 208 72, 85, 96 87-90, 107, 254 13, 231 166

30652-11-0

9-450 5.0-5000 1000-5000

287

287 248

138-14-7 24584-09-6

negative

50-5000

P/0.25 P/1000

P/0.5 P*/1000

P/0.25 P/500

P/0.5 P/2000

0.1-1.5 500-5000

24584-09-6 9004-54-0 1187-42-4 6674-22-2


100-10000 100-6666 100-10000

WP/16 E P/10 N

I N P/80 N

N E P/80 N

I N P/150 N

7.8-125 1000-5000 10-500 156-5000

132-64-9 1210-35-1

negative negative

1.0-333 3.3-3333

N

N

N

N

10-56

24072-75-1

negative

1.0-200

N

N

N

N

10-50

1476-11-5

P/333

3.3-2000

P/0.5

P/0.5

P/7.1

P/7.1

0.5-12 µL

110-57-6

P/33

3.3-2000

P/0.5

I

P/0.004

P/0.006

0.004-6 µL

124-70-9

P/333

100-10000

N

N

N

I

0.044-1

10/7/4752 78-88-6

negative P/100

10-10000 10-3333

P P/0.0048

I P/0.0048

P P/0.018

P P/0.022

2213-63-0 4097-22-7 7481-89-2 69655-05-6 462-95-3

negative negative negative negative negative

100-10000 0.3-66 10-1000 0.3-33 100-10000

P/5 P/173 N P/2433 N

E P/173 N P/3067 N

P/15 P/700 N P/2433 P/500

P/15 E N E P/750

0.25-20 173-800 819-2000 1218-5000 250-5000

P/10

P/50

P/150

P/150

5.0-5000

115900-75-9

refs

293

145, 269

TA98, 100 TA98, 100 TA1535

TA98, 100, 1535

1-20 0.0036-0.03

909-13-7

negative

75-5000

N

N

N

N

1.0-70

2892-51-5

negative

33-10000

N

N

N

N

1500-2500

693-13-0

negative

100-10000

P/25

P/25

P/50

P/50

4-75

46, 121, 130, 196, 293 294 203 249





chemical name dimethoxymethane (methylal) 4-dimethylaminobenzeneazo-1naphthalene 4-dimethylaminobenzeneazo-2naphthalene 4-(N,N-dimethylamino)3-nitrobenzoic acid 2 ethylhexyl ester β-dimethylaminopropylchloride, HCl p-N,N-dimethylaminophenethanol 4-dimethylaminopyridine 4-dimethylamino-4′nitrostilbene 4-dimethylaminostilbene

evaluation

dose (µg/plate)

109-87-5

negative

100-10000

607-59-0

P/10

1.0-10000

613-65-0

P/1

1.0-10000

134682-95-4

P/1000

100-10000

5407-04-5

P/1000

100-10000

50438-75-0

P/333

333-10000

1122-58-3

negative

CAS no.

old eval/ LED

strain

TA98, 100, 1535, 1538 TA98, 100, 1538 TA98, 1537, 1538 TA100

new eval/ LED


new eval/ LED

dose (µg/mL)

N

N

N

N

P/1214

P/1214

P/7

P/9

2.5-2500

N

N

P/3.6

P/3.6

2.6-5000

3000-4980

66

WP/5000

N

P/1750

I

N

N

P/100

I

100-10000

N

N

N

I

not done N

P/10

P/10

10-20

I

P/8.9

P/8.9

2.5-4000

N

N

N

I

TA98, 1535, 1538

4584-57-0

1000-5000

250-2000

191

838-95-9

P/333

0.5-10000

75-78-5

negative

33-6000

99-97-8

negative

3-333

P/0.24

E

P/0.005

P/0.037

0.005-0.31

513-37-1

negative

3-10000

N

N

P/0.06

P/0.09

0.06-0.4

122, 293, 294

512-04-9 102-06-7

negative P/7

100-10000 3-10000

N

N

N

I

300-1000

14, 290

25265-71-8 7691-02-3

negative negative

100-10000 667-10000

N N

N N*

N N

N N

29-60 0.1-2.2

25377-73-5

negative

0.3-10000

N

I

N

N

0.017-0.31

negative negative

0.8-3000 0.33-100

N P/0.005 N

N I N

N N N

N N N

0.001-0.087 0.002-0.1 2262-5000

ecteinascidin (ET-743) electrolytic iron ellagic acid dihydrate ellipticine

112-55-0 110417-88-4 134680-32-3 (+-isomer), 134678-17-4 (--isomer) 114899-77-3 7439-89-6 476-66-4 519-23-3

P/0.33 negative negative

0.033-30 100-10000 333-10000

P/0.5 E N P/0.51

P/0.5 E N P*/0.51

P/10 E N P/0.4

P/10 E I P/0.4

ephedrine HCl ergotamine tartrate estriol ethidium bromide

90-81-3 379-79-3 50-27-1 1239-45-8

negative negative negative P/33

100-10000 10-10000 100-10000 33-3333

N

N

N

N

7.7-108

294

P/1.1

P/1.6

P/1.1

P/1.1

0.1-3

ethyl acrylate

140-88-5

P/15

P/15

P/500

P/500

121, 149, 191, 218, 242, 246 51, 122, 151, 159, 161, 162, 280

ethyl bromoacetate ethyl 2-chloroacetate ethyl 4-chloroacetoacetate ethylene glycol diacrylate

105-36-2 609-15-4 638-07-3


3.3-1000 33-3333 10-1000

WP/1.0 P/4.0 P/2.0

I N P/2.0

P/10 P/40 P/10

I I P/15

0.3-20 0.5-40 0.5-20

2274-11-5

negative

33-6667

P/1.4

E

P/36

E

0.6-65

dimethyldichlorosilane N,N-dimethyl-ptoluidine dimethylvinylchloride diosgenin 1,3-diphenylguanidine dipropylene glycol 1,3-divinyltetramethyldisialazane dodecenylsuccinic anhydride n-dodecylmercaptan dolastatin 10 DTHC [(+/-)-2′deoxy-3′-thiacytidine]

TA98, 100, 1538

refs

TA98, 100, 1537

TA98

TA98, 1537, 1538

0.14-2

0.00025-0.05 1500-5000 5-500 0.2-2.4

5-600

149, 217

110 263

294

62 33 3, 54, 71, 162

28, 280





chemical name

CAS no.

ethylene glycol dimethacrylate ethylene glycol dimethacrylate ethylene glycol dimethacrylate ethylene sulfide 2-ethylfuran 2-ethylfuran 2-ethyl-1,3-hexanediol fecapentaene (C-12)

420-12-2 3208-16-0 3208-16-0 94-96-2 91423-46-0

P/500 negative

100-10000 33-3333

negative

100-10000

(1R)-(-)-fenchone ferric chloride

7787-20-4 10025-77-1

negative negative

ferric orthophosphate ferrocene ferrocene ferrous fumarate ferrous sulfate ferrozine ferulic acid (4-hydroxy3-methoxycinnamic acid) flavone derivative (flavopiridol) 9-fluorenone 4-fluoroaniline 2-fluorobiphenyl β-fluoro-ddA N-fluoromethyl-2hydroxy-N,N-dimethylethaneamminium chloride 2-fluorophenol 2-fluorophenol fullerene mixed extract

51833-68-2 102-54-5 102-54-5 141-01-5 7782-63-0 28048-33-1 1135-24-6

fullerene-rich soot fumaric acid fumaryl acetone geldanamycin, 17-demethoxy17-(2-propenylamino) ginsana glutathione, oxidized glutathione, reduced halichondrin B heptadecylhydroxyethylimidazoline trans,trans-2,4hexadienal hexamethyldisilazane hexamethyldisilazane histidinol N,N′-bis(o-hydroxybenzyl)ethylenediamine-N,N′diacetic acid N,N′-bis(o-hydroxybenzyl)ethylenediamine-N,N′diacetic acid

97-90-5

evaluation negative

dose (µg/plate)

strain

100-10000

old eval/ LED

new eval/ LED


new eval/ LED

dose (µg/mL)

refs 28, 158, 280

P/0.35

E

P/1.1

P/1.2

0.19-1.7

97-90-5

P/1

P/1

P/18

P/18

1-100

97-90-5

N

N

P/0.9

P/1

P/0.05 WP/150 P/250 P/3000 P/0.4

P/0.05 N P/250 N P/0.6

P/0.043 WP/100 P/50 N P/6.1

P/0.052 E* E N N

0.025-0.1 100-300 10-500 500-4000 0.4-10

100-10000 33-10000

P/600 N

N* N

P/500 N

P*/500 I

250-650 0.2-1030

negative negative

100-10000 100-10000

P/1000 negative

100-10000 33-10000

N P/16 P / 5.0 P/920 P/750 N

N P/20 E 9/980 E N

P / 2.0 E P / 20 N P/6.0 N

E I P / 40 N I N

1.5-3000 12-50 5.0-70 1.6-316 2-1000 1000-5000

negative

100-10000

146426-40-6

negative

3.3-1000

N

N

P/100

I

10-150

486-25-9 371-40-4 321-60-8 110143-10-7 459424-38-5

negative P/333 negative negative

3.3-700 100-10000 10-667 100-10000

N P / 800 N E N

I E N N N

N E P/44 WP/300 N

N I N E N

1.5-75 100-1000 1-50 300-500 500-1580

P/0.21 N

N N

P/0.002 N

P/0.003 I

367-12-4 367-12-4

TA100

TA98

TA98

0.09-1.4

247 40, 91, 94, 199, 273, 276, 278 62, 144, 151, 233 123 83 62 62, 74 287

256 298

0.0001-0.6 0.001-0.1

negative

33-5000

110-17-8 62966-21-6 75747-14-7


3.3-5000 333-10000 2.2-660 100-5000

N P/5943 P/1.5 P/30

N P/8000 P/2 P/45

P/5943 N N

P/6971 N N

100-200 2856-8000 0.5-3.5 20-400

27025-41-8 70-18-8


100-10000 100-10000 333-10000

N N P/115

N N E

N N N

N N N

250-1250 3514-9804 50-10000

103614-76-2 95-19-2

negative

1.0-100

WP/5 N

N N

P/6 N

E I

0.5-7.0 0.49-31

294

142-83-6

negative

10-10000

P/1.9

P*/2.5

N

N

0.6-74

66

999-97-3 999-97-3 501-28-0 35998-29-9

negative

667-10000

N N N P/100

I I N P/100

N N N P/1500

N I N P/2500

2-5 4.2-9 2454-5000 100-2500

P/100

P/100

P/1500

P/2500

25-5000

35998-29-9

11, 18, 236 76, 293

30, 37, 90, 254





chemical name γ-hydroxybutyrate N,N-bis(2-hydroxyethyl)-p-toluidine 2-(hydroxyimino)-Nphenylacetamide oxime (isonitrosoacetanilide) 2-hydroxy-4-methoxybenzophenone 4-hydroxy-4-methyl-2pentanone 4,4-bis(4-hydroxyphenyl) valeric acid 4-hydroxyquinazalone ICR-170 (acridine mustard) imidazolidinyl urea

CAS no.

evaluation

dose (µg/plate)

591-81-1 12/1/3077

negative negative

100-10000 333-10000

1769-41-1

negative

131-57-7

strain

old eval/ LED

S9-activated

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

N

N

E

I

400-1943

10-10000

P/613

E

N

N

4-871

negative

3-333

P/37

N

P/37

E

18-60

123-42-2

negative

100-10000

E

N

E

N

3000-5000

126-00-1

negative

100-10000

491-36-1 146-59-8

negative

100-10000

P/2000 0.08

E P/0.08

WP/750 P/1

P/750 I

750-2500 0.08-2

39235-46-9

P/333

3,3′-iminodipropionitrile 3-indazoline indole-3-carbinol 4-ipomeanol iron dextran isoamyl nitrite isoamyl nitrite isoamyl nitrite (retest) isobutyl nitrite

111-94-4 7364-25-2 700-06-1 32954-58-8 9004-66-4 110-46-3 110-46-3 110-46-3 542-56-3

negative negative negative negative negative P/1000

100-10000 100-10000 33-3333 100-10000 100-10000 100-66667

N P/100 P/100

N P/200 P/100

P/3500 N P/30

E N P/40

3000-5000 25-2000 10-160

P/1000

10-10000

E P/0.6 P/0.69 P/0.07 P/0.009

N E P/1.5 I P/0.009

P/3000 P/0.2 P/0.61 I P/0.11

E P/0.3 P/0.49 N P/0.15

50-5000 0.15-0.7 0.3-1.8 0.03-2.2 0.0025-0.22

isobutyl nitrite isobutyl nitrite (retest) isoeugenol isophthalodinitrile (1,3-dicyanobenzene isopropenyl acetate juglone kaempferol

542-56-3 542-56-3 97-54-1 626-17-5

P/0.25 E P/0.06 N

E E P/0.1 N

P/0.1 P/0.45 N N

P/0.1 P/0.5 N N

0.1-1 0.03-0.7 0.007-0.1 600-1000

P/3000 P/0.17 P/30

I P/.19 P/40

E WP/4 P/18

N E E

500-4000 0.05-4.0 18-245

P/400

I

P/250

E*

50-400

P/62 N

P/74 N

P/36 P/300

E E

10-87 50-500

33-10000

negative negative

100-10000 100-10000

294

55, 122, 149, 163

TA98, 100

TA1535

TA98, 100, 1535

108-22-5 481-39-0 520-18-3

negative

100-10000

P/3.3

3.3-10000

3375-84-6 147318-81-8 84-79-7 105-74-8 105-74-8

negative negative negative negative negative negative negative

100-10000 100-10000 1-100 100-10000 15-2500 10-4444 100-10000

N

I

N

I

61790-14-5 60-33-3

negative negative

100-10000 100-10000

P/0.061 N

E N

P/0.1 N

P/0.25 N

0.01-0.25 0.005-0.07

linolelaidic acid linolenic acid luteolin (3',4',5,7tetrahydroxyflavone) maleimide

506-21-8 463-40-1 491-70-3


33-10000 0.6-500 10-10000

N N

N I

N N

N N

0.005-0.05 0.005-0.04

541-59-3

P/3.3

0.3-50

P/28

I

P/14

P/14

0.14-19

manganese naphthenate menthyl anthranilate Merck L651582 6-methoxy-2-benzothiazolamine

1336-93-2

negative

10-10000

N

I

P/0.15

E

0.02-0.1

134-09-8 99519-84-3 1747-60-0

negative negative P/0.1

667-10000 1.0-3333 0.1-3000

N N N

N I N

N N P/2

E N P/7

kava pure extract kava kava (NTP) KIPA (oxazolidinone) KNI-272 lapachol lauroyl peroxide lauroyl peroxide (new batch) lead naphthenate linoleic acid

refs

TA98, 100, 1535, 1537

228, 277 62, 153 63

63, 84, 122, 157, 178

73 113

268 146, 226

98

TA98, 100

TA98, 100, 1535, 1537, 1538

340-500

5-52 1.1-100 2-436

111, 120, 185, 239, 294 120, 239 41

184





chemical name

CAS no.

o-methoxycinnamic aldehyde

1504-74-1

evaluation

dose (µg/plate)

negative

10-1000

old eval/ LED

strain

P/11

new eval/ LED I

S9-activated old eval/ LED P/57

new eval/ LED I

dose (µg/mL) 5-89

2-methoxyestradiol

362-07-2

E

I

P/80

E

1.5-90

3-methoxypropylamine

5332-73-0

negative

100-10000

N

N

N

N

500-4000

4-methoxystyrene

637-69-4

negative

3.3-10000

WP/175

N

P/100

E

50-250

methyl acrylate

96-33-3

P/30

P/40

P/75

P/75

20-200 25-500

2-methylbenzothiazole

120-75-2

negative

100-10000

P/500

P/500

N

N

4-(6-methyl-2-benzothiazolyl)benzenamine

92-36-4

P/1

0.1-4500

TA98, 100, 1537, 1538

P/57

P*/89

P/5

P*/5

trans-2-methyl2-butenal

497-03-0

P/333

333-10000

TA100

P/150

I

N

N

10-250

3-methyl-3-buten2-one

814-78-8

negative

100-10000

P/20

P/20

P/30

P/35

10-45

methyl carbamate

598-55-0

negative

333-10000

N

N

N

N

4837-10000

65 136

163, 280, 294

5-121

methyldichlorosilane

75-54-7

negative

33-3333

N

N

N

N

0.18-0.5

methylene bis (thiocyanate)

6317-18-6

negative

0.3-33

E

N

N

N

0.17-22

methylene blue

61-73-4

P/33

0.03-2000

P/36

P/36

P/2

P/2

methylene chloride

75-09-2

negative

100-6666

N

N

N

N

TA98, 100

refs

0.9-87 1-8.7

19, 121, 122, 149, 159, 175, 284, 293

97, 121, 281 56, 58, 95, 115, 121, 198, 245, 259, 285

methyl fluorosulfonate

421-20-5

negative

100-6666

P/0.15

P/0.15

P/0.22

E

0.03-0.3

2-methylimidazole

693-98-1

negative

667-10000

N

I

N

I

1000-2000

187

methyl isocyanate

624-83-9

negative

10-1000

P/0.7

P/0.79

N

N

0.35-5.2

30, 154, 155

3-methyl-5-isothiazolamine hydrochloride

52547-00-9

negative

333-10000

P/100

I

P/357

E

100-871

27, 149

2-methyl-2-(methylthio) propionaldoxime (aldicarb oxime)

1646-75-9

negative

100-10000

N

E

N

N

1.1-1.7

219, 253

2-methyltetrahydrofuran

96-47-9

negative

100-10000

N

N

N

I

1500-5000

methyl trifluoromethanesulfonate

333-27-7

negative

100-10000

P/0.5

P/0.5

P/0.5

P/1.1

8-methyl-N-vanillylnonanamide (dihydrocapsaicin)

19408-84-5

negative

10-3333

negative

100-5000

michellamine B diacetic acid salt

7, 121

0.5-3.1 80

N

N

P/300

E

25-500

mitindomide

10403-51-7

negative

40-5000

P/92

I

P/58

P/90

molybdenum trioxide

1313-27-5

negative

333-10000

N

I

P/700

P/1600

58-349

naphthalene

91-20-3

negative

3.3-10000

N

N

P/14

P/14

(()-naringenin (4′,5,7trihydroxyflavanone)

480-41-1

negative

33-10000

2-nitrobenzaldehyde

552-89-6

P/100

33-10000

TA98, 100

P/100

N

N

N

30-150

36, 119, 121, 241

3-nitrobenzaldehyde

99-61-6

P/333

33-10000

TA100

WP/150

N

P/1000

P/1000

25-1000

119, 227, 241

4-nitrobenzaldehyde

555-16-8

P/100

33-10000

TA98, 100

P / 50

N

P / 900

E

1.5-900

36, 119, 121, 168, 241

m-nitrobenzoyl chloride

121-90-4

P/333

33-3333

TA98, 1538

P/543

I

P/1800

I

400-3000

119, 294

486-4357

122, 135, 180

8-87

39, 112, 121, 122, 149, 173, 177, 224 15, 147





chemical name

CAS no.

evaluation

dose (µg/plate)

strain

old eval/ LED

S9-activated

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

refs

p-nitrobenzoyl chloride

122-04-3

P/333

3.3-333

TA98

N

N

N

N

10-430

119, 294

4-nitrochalcone

1222-98-6

P/10

100-10000

TA98, 100

N

N

N

N

1-25

66, 168, 213

4-nitrocinnamaldehyde

1734-79-8

P/1

1.0-500

TA98, 100

P/2

P/3

N

N

0.5-200

P/33

1.0-50

TA100

N

I

N

I

2.5-50

2-(2-nitro-1-H-imidazol1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide

66

5-nitroindazole

5401-94-5

P/10

33-10000

TA98, 100

N

N

WP/900

N

50-1000

36, 121

5-nitroisatin

611-09-6

P/33

33-10000

TA98, 100

P/50

P/75

P/10

E

10-100

36, 121

nitromethane

75-52-5

negative

33-10000

P/11

E

N

N

4.6-22

44, 53, 119, 179

5-(4-nitrophenyl)2,4-pentadien-1-al

2608-48-2

P/0.1

P/3.5

E

E

E

2-199

5-(4-nitrophenyl)2,4-pentadien-1-al

2608-48-2

P/4

E

E

N

3-150

N-nitroso-N-methyl-paminobenzoic acid, 2-ethylhexyl ester A

122021-01-6

N

N

N

N

0.001-0.2

64

N-nitroso-N-methyl-paminobenzoic acid, 2-ethylhexyl ester B

122021-01-6

N

N

N

N

0.41-1

64

N-nitrosonornicotine

16543-55-8

P/100

33-10000

TA1535

N-nitrosopiperidine

100-75-4

P/33

10-10000

TA98, 100, 1535

nonanal

124-19-6

negative

nordihydroguaiaretic acid

500-38-9

negative

octamethylcyclotetrasiloxane

556-67-2

negative

0.01-66

TA98, 100, 1535, 1537, 1538

667-10000

43, 196, 291 N

N

3.3-333

N

E

N

E

0.013-0.14

1.6-420

P/4

P/6

N

N

24-250

negative

333-10000

N

I

N

N

0.005-1

333-10000

P/0.016

P/0.02

N

N

0.01-1

octamethyltrisiloxane

107-51-7

negative

oxazolidine E

101707-05-5 or 7747-35-5

P/100

33-750

P/0.5

P/0.5

0.1-6

penclomedine

108030-77-9

P/1.9

P/1.9

108030-77-9

P/3.3

3.3-5000

N

N

P/21

P/21

4-60

pentamidine isethionate

140-64-7

negative

33-2000

N

N

N

N

1-74

cis-2-pentenenitrile

25899-50-7

negative

333-10000

536-59-4

negative

33-10000

perillyl alcohol

39

110, 275

TA98, 100

penclomedine

perillyl alcohol

42, 64, 86, 121, 122, 142, 149, 201, 202, 211, 282, 297

1.4-2.5 38

P/0.74

P/0.74

P/0.0091

P/0.014

N

N

P/50

P/200

536-59-4

N

N

N

N

50-300

1,10-o-phenanthroline

66-71-7

P/0.75

P/1.0

P/25

P/50

0.5-50

223, 294

phenylglyoxal monohydrate

1074-12-0

P/3

P/3

N

N

0.5-100

10, 60, 282

P/33

33-3333

TA98, 100

0.004-1 50-300

o-phenylphenol

90-43-7

negative

3.3-1000

N

N

P/24

P/24

1-50

122, 174

o-phenylphenol, sodium salt tetrahydrate

132-27-4

negative

67-3333

N

N

P/31

E

1-87

75, 122

3-phenylpropanol

122-97-4

N

N

N

N

0.1-1

3-phenylpropionic acid

501-52-0

N

N

N

N

500-8091

5-phenyl-2,4-thiazolediamine hydrobromide

6020-54-8

negative

P/300

I

P/1571

I

300-2714

27

phloretin

60-82-2

negative

3.3-1000

phthalazine

253-52-1

negative

100-10000

P/3000

E

P/1000

P/1000

250-3000

165

phthalhydrazide

1445-69-8

negative

100-10000

N

N

P/1000

P/1000

500-2000

333-10000





evaluation

dose (µg/plate)

negative

100-10000


100-10000 100-6666 100-5000

120-57-0 481-42-5 518-28-5 902-86-2 13746-66-2 50-03-2 125-33-7 107-03-9 76578-12-6

negative negative negative negative negative negative P/3333 negative negative

100-10000 0.33-100 100-10000 667-10000 100-10000 100-10000 33-10000 3-333 75-5000

71-23-8 79-10-7 1072-43-1 925-60-0 543-67-9 543-67-9 290-37-9


333-10000 33-5000 100-6667

negative

100-10000

negative

333-10000

pyrazoloacridine

99009-20-8

P/1

1.0-500

pyridostigmine bromide quercetin

101-26-8

negative

100-10000

117-39-5

P/33

questran quinidine quinobene quinoxaline rutin

58391-37-0 56-54-2 140942-13-8 91-19-0 153-18-4

negative negative negative negative P/100

100-10000 50-5000 100-10000 100-10000 100-10000

saffron sesamol silicone phthalocyanine (sodium) 8-CL cAMP sodium EDTA

11012-59-2 533-31-3 135719-28-7 41941-56-4 139-33-3


48-4820 33-5000 5-80 40-5000 33-10000

sodium ferric EDTA sodium formate sodium lauroylisethionate sodium selenite pentahydrate strontium carbonate styrene

15708-41-5 141-53-7 7381-03-1


33-10000 666-10000 33-1600

26970-82-1

negative

33-3333

1633-05-2 100-42-5

negative negative

succinic acid, 2,2dimethyhydrazide (Alar)

1596-84-5

negative

chemical name

CAS no.

phyllanthoside phytic acid picolinic acid (-)-β-pinene piperidinooxy, 4hydroxy-2,2,6,6tetramethyl (tempol) piperonal plumbagin podophyllotoxin polyvinylchloride latex potasium ferricyanide prednisone primaclone 1-propanethiol propanoic acid, 2-[4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy](-)-(S)1-propanol propenoic acid propylene sulfide n-propyl acrylate n-propyl nitrite n-propyl nitrite pyrazine

63166-73-4 83-86-3 98-98-6 18172-67-3 2226-96-2

33-10000

S9-activated

strain

old eval/ LED

N E N P/1000

N P/1500 N P/500

N E I P/750

1000-5000 150-5000 0.003-0.14 250-5000

287 288

TA102

N P/750 P/0.018 P/500

P/1000 P/0.075 N N N N N N P/10

P/1000 N N N N N* N N P*/10

WP/500 P/4 N N P/4000 N N P/0.024 P/50

E E N N E I N E P/50

250-1000 0.015-5.0 0.1-75 0.3-4.4 1000-5000 100-750 970-2000 0.011-0.61 10-500

100 98, 284

P/0.18 P/0.17 P/30 P/0.3 P/0.8 N

P/0.18 P/0.2 P/30 P/0.3 I N

P/1.1 P/0.1 P/400 P/0.2 P/4.75 N

P/1.1 E P/400 P/0.2 P/4.75 N

0.11-2.2 0.02-0.2 10-400 0.2-2.5 0.089-6.5 2286-10000

P/1.1

P/1.5

P/2.1

P/2.1

0.31-15

N

N

WP

E

3000-5000

TA1535

TA98, 1537, 1538

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

TA98, 100

refs

79, 251

293 62, 144 122, 181

28, 294

63 2, 78, 261

19, 41, 84, 121, 122, 143, 146, 176, 190, 221, 234, 256, 279 N N E WP/1500

N N N N

N N N P/50

N I N P/2500

1602-3300 108-300 15-25 20-1500

E P/15

I P/30

E P/8

I P/26

714-4957 8-260

N E

N N

N E

N N

195-400 250-2000

P/2500 P/10000 N

E N N

P/12.5 P/8714 N

P/50 E N

P/11

P/11

P/1.3

P/1.7

0.35-13

333-10000 1.0-333

N N

N I

N E

N N

1786-5000 0.05-0.18

667-10000

N

N

N

N

2400-5000

TA98, 100

243, 293 2 59, 220-222 1 122

67, 70, 76

0.026-325 3571-10000 16-149

19, 24, 39, 49, 68-70, 122, 293 294





strain

old eval/ LED

new eval/ LED

old eval/ LED

new eval/ LED

dose (µg/mL)

chemical name

CAS no.

succinylacetone (4,6dioxoheptanoic acid) succinylated concanavalin A sulfamethizole sulfanilamide sulfathiazole tamoxifen tamoxifen citrate salt terbium polyoxometalate m-terphenyl o-terphenyl p-terphenyl R-terpineol 1,2,4,5-tetrachlorobenzene tetracyanoethylene tetraethyl orthosilicate (ethyl silicate) tetraglycine hydroperiodide tetrahydronaphthalene tetramethylsuccinonitrile tetrathiomolybdate 2-thiazolamine

51568-18-4

negative

33-10000

N

N

P/1700

P/2600

714-3500

55128-23-9

negative

33-5000

N

N

N

N

435-3996

144-82-1 63-74-1 72-14-0 10540-29-1 54965-24-1


2-200 100-10000 0.008-433 1.0-1000 1.0-1000

N N N

N N N

N N N

E N N

1143-8714 4.9-250 1000-10000

144113-80-4

negative

100-10000

P/520

P/520

P/520

P/640

520-1000

92-06-8 84-15-1 92-94-4 98-55-5 95-94-3


667-10000 667-10000 667-10000 10-1000 10-1000

N N N N N

N N N N N

P/24 N P/11 N N

E N E N N

1-50 1-37 1-1000 0.14-0.65 121-250

670-54-2 78-10-4

negative negative

1.0-2000 100-10000

N N

I N

N E

I N

22-90 250-1300

P/43

I

N

I

20-1231

119-64-2 3333-52-6

negative negative

3.3-10000 667-10000

P/45 N

N N

E N

E N

16330-92-0 96-50-4

negative P/3333

50-5000 100-10000

P/50 P/443

P/100 E

P/75 P/643

P/100 E

thiazole thionyl chloride

288-47-1 7719-09-7

negative P/33

333-10000 33-3333

N P/0.11

N E

N N

N I

1-7 0.024-0.31

thiophene thujone p-toluenesulfonic hydrazide o-tolunitrile tolyltriazole 2,4,6-tribromophenol tributylborane

110-02-1 546-80-5 1576-35-8


10-6667 100-10000 100-10000

P/1.4 N P/500

P/1.4 N P/1000

P/0.24 P/40 P/1500

I E E

0.05-1.8 15-300 100-2400

529-19-1 29385-43-1 118-79-6 122-56-5

negative negative negative P/333

100-10000 100-10000 10-333 10-10000

N P/750 P/90 N

N I P/120 N

P/0.05 P/25 N N

P/0.1 P/50 N N

0.02-0.61 12.5-750 1-120 50-400

4252-78-2

negative

1.0-500

N

N

N

N

0.03-18

13608-87-2

negative

10-667

N

I

N

N

27-75

75-69-4

negative

10-3333

N

N

N

I

0.5-30

7673-09-8 3764-01-0

negative negative

0.8-80 3.3-500

N P/0.75

N I

E P/30

P/27 P/30

1-56 0.1-30

10025-78-2 78-08-0 994-28-5

negative negative

33-2000 33-10000

N N N

N N I

N N N

N N N*

0.02-0.19 0.1-0.9 0.01-0.15

535-83-1 520-36-5

negative negative

333-10000 33-10000

N

I

N

I

1017-7051

78 20, 41

4460-86-0

negative

33-3333

N

N

P/1428

E

914-4000

57, 294

1640-39-7

negative

33-10000

WP/200

N

P/100

I

100-200

118-12-7

P/1000

100-10000

N

N

P/10

P/40

N

N

P/100

P*/100

2,2′,4′-trichloroacetophenone 2′,3′,4′-trichloroacetophenone trichlorofluoromethane (freon 11) trichloromelamine 2,4,6-trichloropyrimidine trichlorosilane triethoxyvinyl silane triethylgermanium chloride trigonelline 4′,5,7-trihydroxyflavone (apigenin) 2,4,5-trimethoxybenzaldehyde 2,3,3-trimethylindolenine 1,3,3-trimethyl-2methyleneindoline 1,3,3-trimethyl-2methyleneindoline

evaluation

dose (µg/plate)

S9-activated

7097-60-1

118-12-7

TA98, 1535, 1538 TA100, 102

TA100

TA98, 100

TA98, 100

1-50 1500-2000 50-500 100-1500

10-300 100-2600

refs

37 237, 238

93

140

109, 293

27

132

1, 294 16, 112 293 293 294

113, 294





chemical name

CAS no.

trimethylolpropane triacrylate trimethylolpropane triacrylate trimethylolpropane trimethacrylate trimethyloxonium hexachloroantimonate 2,4,7-trinitrofluoren-9-one

15625-89-5

evaluation negative

dose (µg/plate)

old eval/ LED

strain

100-10000

15625-89-5

S9-activated

new eval/ LED

old eval/ LED

P/0.0003

I

P/0.03

P/0.0007

P/0.0007

not done

new eval/ LED

dose (µg/mL)

P/0.03

0.0003-0.035 0.0001-0.0009

3290-92-4

negative

33-10000

N

N

N

N

54075-76-2

negative

10-6666

N

N

P/18

P/29

0.69-29

129-79-3

P/1

P/1.8

P/1.8

P/23

P/35

0.5-61

triphenylantimony tropolone uniroyal JR urocanic acid valeraldehyde vanadium pentoxide

603-36-1 533-75-5 135812-34-9 104-98-3 110-62-3 1314-62-1

negative negative negative negative negative negative

100-6666 1.0-333 55-5000 100-10000 100-10000 333-10000

E P/3.9 N E P/100 N

N P/7.8 N N P/150 N

P/14 P/31 N E N N

E N N N N N

5-100 200-500 60-500 10-100

vinyl acetate

108-05-4

negative

333-10000

P/1.9

P/1.9

P/1.8

P/1.8

1.8-5

p-vinyl guaiacol m-xylenediamine yohimbine HCl zearalenone

7786-61-0 1477-55-0 146-48-5 17924-92-4


33-4000 100-10000 100-10000 3.3-10000

N N N

E N I

N N N

N N I

zenedrine RFA-1 zinc naphthenate zinc oxide

12001-85-3 1314-13-2


100-10000 667-10000 333-10000

7699-43-6

negative

33-10000

zirconium oxychloride

1-100

TA98, 100, 1535, 1537, 1538

0.021-0.2

refs 28, 52, 163, 265 28, 52, 163, 264 28, 52 294 124, 250

2-20

0.009-0.04 50-400 10-50

122, 135, 215 19, 67, 116, 137, 167, 285 260 13, 122, 129, 151, 200, 262, 286

P/0.022 P/4.9

P/0.022 P/4.9

P/0.02 P/18

I P/24

N

N

N

N

0.0033-0.05 1-31

229, 230, 255, 290

716-2000

a Abbreviations used in the mouse lymphoma study: LED, lowest effective dose; P, positive result; N, negative; WP, weak positive; E, equivocal; and I, inconclusive. *The conclusion presented is based on data available, although the full requirements for a valid test (e.g., minimum of four concentrations with mutant frequency data) were not met.

response as P/dose expressed numerically as well as the strain(s) testing positive. This is indicated as the LED (lowest effective dose) in the mouse lymphoma studies. In the Salmonella mutagenicity assay, each chemical was tested without metabolic activation and with liver S9 preparations from Sprague-Dawley rats and Syrian golden hamsters. Unless limited by toxicity, each chemical was tested to the upper limit of 10000 µg/plate. In Table 1, references are indicated for other mutagenicity tests reported in the literature; the reference listing can be found in the Supporting Information (Table 1). The tabular data also include the PubMed abstract identification number, when available, for convenience. The responses of the tests in the mouse lymphoma mutagenicity assay are also summarized in Table 1 of the Appendix, and the complete data are in the Supporting Information (Table 4). Each chemical was tested without metabolic activation and with liver S9 preparations from Sprague-Dawley rats. The lowest concentrations at which a 2-fold increase in mutant frequency was achieved are also given in Table 1 for those tests eliciting a positive response as P/dose expressed numerically. The data have been evaluated under the traditional criteria described above (28) (old eval columns) as well as the current international “harmonization” recommendations (new eval columns). This will aid the reader in interpreting these and other

mouse lymphoma mutagenicity assay data in the literature. Briefly, a compound is currently considered positive if a concentration-related increase in mutant frequency is observed and one or more dose levels with 10% or greater total growth exhibit mutant frequencies of g100 mutants per 106 clonable cells over the background level. The lowest concentrations at which an increase in mutant frequency of g100 mutants per 106 clonable cells over the background level wasachieved are also given in Table 1 for those tests eliciting a positive response. (25, 30) The term LED refers to the lowest dose at which a positive result was noted and stands for lowest effective dose. Compounds that were positive in the assay in either the presence or the absence of metabolic activation all elicited an increase in small colonies when compared to the colony size distribution in the untreated control. The precise distribution of large and small TFT-resistant mutant colonies appears to be the characteristic mutagenic “fingerprint” of carcinogens in the L5178Y TK+/- system (28, 31). Some chemicals (e.g., ethyl methanesulfonate) produce relatively greater numbers of large colonies, while others (e.g., hycanthone) induce predominantly small colony TK-/- mutants. Clive and co-workers (28) and Hozier et al. (32) have presented evidence to substantiate the hypothesis that the small colony variants carry chromosome aberrations associated with chromosome 11, the chromosome


on which the TK locus is located in the mouse (33). They suggested that large colony mutants received very localized damage, possibly in the form of a point mutation or small deletion within the TK locus, while small colony mutants received damage to collateral loci concordant with the loss of TK activity. This view was substantiated by the demonstration of two different types of damage in the two alleles of the TK gene at the molecular level (34, 35).

Appendix Following is a table that contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay (Table 1). Acknowledgment. We recognize the contribution of Michelle Cooper (NCI), Daundaun Yang (a summer high school volunteer at NCI), and Grace McMonagle (BioReliance) who input a good portion of the raw data from paper copies of the studies. Their efforts are highly appreciated and critical to the successful completion of the project, which lasted several months longer than imagined at the initiation. The mention of commercial products, their source, or their use in connection with materials reported herein is not to be construed as either actual or implied endorsement of such products. Early mutagenicity tests were run by C. Anita Bigger, Andrea Rogers-Back, Timothy Lawlor, John Harbell, Steve Haworth, and Valentine Wagner at Microbiological Associates under a series of contracts to Thomas P. Cameron at the NCI Division of Cancer Etiology. Supporting Information Available: Table 1 of reference numbers, PubMed ID numbers, and reference citations; table 2 containing structure drawings and CAS numbers; table 3 containing dose and all Salmonella strain data; and table 4 containing data for nonactivated and S9-activated cultures in the mouse lymphoma test. This material is available free of charge via the Internet at http:// pubs.acs.org.

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