Group C-10 化学構造 (Chemical Structure)  

Clofibric acid (クロフィブリン酸)        
  
 CAS: 882-09-7 Medicine  MW: 214.65
CA CHL/IU Min ( 0.5 mg/ml, +S9), 3-18h: D20= 0.48; TR= 40)
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998) (Tables in English)

Clomeprop
(クロメプロップ) 
   
 84496-56-0 Petiscide  324.2
REC B. subtilis Max (  3.3 mg/disk, ±S9)
1)
AM Sal./E. coli Max (  6.6 mg/plate ±S9)
1)
CA CHL/IU Max ( 0.33 mg/ml, ±S9) (a few poly)
1)
MNv Mice/CD-1 Max ( 3.0 mg/kg)
1)
1) Mitsubishi Yuka Co., Ltd.: J. Pesticide Sci., 16, 125-128 (1991)

Coal tar creosote (コールタール クレオソート)
   
  8001-58-9  Industry     MW: (Mixed)
  
【Note】 (Cited from CICADs Documents, 62, 2004)

   A number of the components of creosote (e.g., PAHs) are known to be mutagenic (IPCS, 1998).

In vitro assays

   A summary of in vitro genotoxicity assays carried out for various creosotes with bacterial (Ames/Salmonella test, assays with Escherichia coli) and mammalian (mouse lymphoma cell assay, sister chromatid exchange test with Chinese hamster ovary cells, chromosomal aberrations in human lymphocytes) test systems (Simmon & Poole, 1978; Bos et al., 1983, 1985; Nylund et al., 1992; IUCLID, 2000). Almost all creosotes tested showed mutagenic activity after metabolic activation (S9 mix) in the conventional Ames/Salmonella assay with strain TA98. Further, the nitroreductase overproducing strain YG1021 and the O-acetyltransferase overproducing strain YG1024 were tested, which have increased sensitivity to detect mutagenicity of aromatic nitro and amino compounds. Positive results were also obtained with several other Salmonella TA or YG strains or with the mouse lymphoma cell assay and the sister chromatid exchange test with Chinese hamster ovary cells. Negative results have been observed with the Salmonella tester strain TA1535 (which may be less sensitive in this case or indicative of other mutation types). Depending on creosote type tested, the Salmonella assay with tester strain TA100 as well as the SOS chromotest with Escherichia coli PQ37 gave positive and negative responses, thus indicating differences in mutagenic activity between different creosotes. There were also differences in the relative strengths of genotoxic responses. For example, Nylund et al. (1992), testing four creosote samples (about 85 components identified, 96?98% of total composition; see also Table 3: F, G) from different countries, found the same order of potency when the creosotes were tested both in the Ames/Salmonella assay using strains TA98 and YG1024 and in the sister chromatid exchange test with metabolic activation. The order of potency was: Danish > former Soviet > German > Polish creosotes.
   
   In a two-stage transformation assay, creosote (no specification given) enhanced transformation of Syrian hamster embryo cells initiated with BaP, thus indicating tumour-promoting activities (Sanner & Rivedal, 1988).

   Attempts have been made to identify the compounds or groups of compounds in different creosotes responsible for the mutagenic activity. As a result, several fractions of different creosotes have also been demonstrated to be mutagenic to Salmonella typhimurium TA98 in the presence of metabolic activation. The creosotes were fractionated by means of TLC (Bos et al., 1984a) or distillation (Nylund et al., 1992). Three of seven TLC fractions of creosote P1 were highly mutagenic: one contained unidentified more polar compounds, the second contained BaP, and the third contained benz[a]anthracene (Bos et al., 1984a). Both fractionation and mutagenicity profiles differed between the four different creosotes (Danish, German, Polish, former Soviet) tested by Nylund and co-workers. A common feature in the tests with Salmonella strains TA98 and TA100 (plus S9 mix) was that the mutagenicity appeared in the distillation fractions having the highest boiling point ranges (>290 °C) and high concentrations of known mutagenic PAHs (chrysene, benzo[e]pyrene, benzo[k]fluoranthene, BaP, dibenzo[a,h]anthracene, benzo[ghi]perylene). Although the intact creosotes contained lower concentrations of the six PAHs than these fractions, their mutagenic response was mostly higher; only a single fraction of one creosote showed slightly higher mutagenicity than the original creosote (Nylund et al., 1992).

   Components suggested to be responsible for the mutagenicity of creosotes include mainly PAHs, but also aromatic amines and certain azaarenes (e.g., Sundstrom et al., 1986). Comparisons between mutagenic activities and concentrations of known mutagenic PAHs in several creosotes (see above) and some of their corresponding fractions suggested synergistic and antagonistic interactions (Nylund et al., 1992).

   The mutagenic action of creosote (Cindu Chemicals, The Netherlands) vapour (generated at 37 °C) has been attributed to fluoranthene, based on the so-called taped plate assay with Salmonella strains TA98 and TA100 in the presence of S9 mix (Bos et al., 1987); however, this test was negative with the creosotes examined by Nylund et al. (1992).

Urine samples of rats injected intraperitoneally with 250 mg creosote/kg body weight showed elevated mutagenic activity in the Ames test with Salmonella typhimurium TA98 in the presence of metabolic activation and beta-glucuronidase (Bos et al., 1984b,c). The same test (metabolic activation not reported) was positive with urine samples from rats treated orally with creosote (lot CX1984; 50 mg/kg body weight per day) over a 5-week period (Chadwick et al., 1995).

Human urine samples collected from wood impregnation plant workers (n = 6) at the end of shift and tested according to the Ames Salmonella test with strain TA100 did not show any exposure-related increase in mutagenicity (Nylund et al., 1989). The same was true for urine samples from three workers of another wood impregnation plant, when tested with Salmonella strain TA98 (plus S9 mix and beta-glucuronidase): spot wipe samples collected from several contaminated surfaces (= 5; solvent: acetone or alcohol) in the working environment of this plant gave positive mutagenic results with the tester strain TA98 in the presence of S9 mix; the extraction with acetone revealed higher mutagenic values than extraction with alcohol (Bos et al., 1984b,c).

   Several genotoxicity tests performed with creosote-contaminated soils or sediments gave positive results.

   The mutagenic activity (as monitored by the Ames test with Salmonella typhimurium TA98, +/- S9 mix) of a creosote/PCP waste sludge (from an active wood treatment facility) applied to soil was found to persist in surface soil at least 350 days after sludge application. During lysimeter experiments, most of the mutagenicity was detected in surface soil extracts, with weaker responses in leachate samples (Barbee et al., 1996). Similarly, the crude fraction of bottom sediment waste collected from a sediment pond of a plant using both PCP and creosote was mutagenic in the Ames assay with Salmonella typhimurium TA98 (plus S9 mix), with a total activity approximately equal to the sum of the activities of three (i.e., acid, base, neutral) fractions (Donnelly et al., 1987). A weak mutagenicity in the Salmonella Ames assay against strain TA98 (with metabolic activation) was found in the PAH fraction of soil collected from a wood treatment plant (in operation from 1924 to 1987; using 100% creosote, 50% creosote mixed with other oils and oil carrier, PCP, etc.; oil content 3-6 w/w % of soil; PAH content not quantified) and subjected to Soxhlet extraction with DCM and class component chromatographic separation (Zemanek et al., 1997).

   Soil samples taken in 1996 from a former creosote wood treatment facility (in operation from 1917 to 1972) with maximum PAH concentrations of 3000 mg/kg dry soil were tested with the Ames Salmonella assay using the tester strains YG1041 and YG1042. The creosote soil extracts (extraction agent: DCM) were found to be moderately mutagenic with metabolic activation (S9 mix) and were non-mutagenic without metabolic activation. However, some bioremediation techniques resulted in an increased mutagenicity despite success in reducing the total PAH concentration, probably due to the presence of nitrogen-containing heterocycles (Brooks et al., 1998; Hughes et al., 1998).

   A soil sample from a hazardous waste site contaminated with creosote (no further details) was assayed by a micronucleus test with Tradescantia. Cuttings of Tradescantia clone 4430 were exposed for 30 h to different solutions of aqueous soil extracts (initial total PAH concentration in the soil: 5749 mg/kg, weight basis not specified). The micronucleus frequencies increased in a concentration-dependent manner. A further increase in genotoxicity was seen in soil samples (containing indigenous microflora) incubated for 8 weeks, which was presumed by the authors to be due to the generation of water-soluble metabolic intermediates by the microorganisms (Baud-Grasset et al., 1993).

Sediment samples collected in 1994 near a wharf, which was treated before immersion in the water with creosote (no specification) some months before (1993), and extracted with DCM, followed with an exchange into DMSO, were tested in rainbow trout (Oncorhynchus mykiss) hepatocytes using the nick translation assay (NTA) and the alkaline precipitation assay (APA). Total PAH concentrations in these sediments ranged from 0.14 to 209 mg/kg dry weight, with the number of PAHs varying from 6 to 16. PAH concentrations and genotoxicity were higher in samples from the intertidal section than from the subtidal section. Samples closest to the wharf (1 m and 5 m) showed more genotoxicity than those farthest (40 m and 50 m) from the wharf. Whereas 80% and 60% of the intertidal samples were genotoxic according to NTA and APA, respectively, only 10% and 30% of the subtidal samples were positive in the NTA and APA, respectively. There were some correlations between levels of some PAHs (naphthalene, acenaphthylene, fluorene, phenanthrene, anthracene, and pyrene) and the NTA results, but the relevance of this finding remains unclear (Gagne et al., 1995).

In vivo assays

Creosotes

   A commercially available coal tar creosote (Lot No. MOP9328, manufactured by Nakarai, Kyoto, Japan) has been tested in a collaborative study using the rodent micronucleus assay. CD-1 male mice (n = 5 or more) received two intraperitoneal injections (with an interval of 24 h) of creosote (in olive oil) at a concentration of 92.5, 185, or 370 mg/kg body weight. The frequency of micronucleated polychromatic erythrocytes in bone marrow increased dose dependently and with statistical significance (24 h after final treatment). A single intraperitoneal treatment of 370 mg/kg body weight (corresponding to about 80% of the LD50) also induced micronuclei (Morita et al., 1997).

References

Baud-Grasset S, Baud-Grasset F, Bifulco J, Meier J, Ma T (1993) Reduction of genotoxicity of a creosote-contaminated soil after fungal treatment determined by the Tradescantia-micronucleus test. Mutation Research, 303(2): 77-82.

・Bos RP, Hulshof CTJ, Theuws JLG, Henderson PT (1983) Mutagenicity of creosote in the Salmonella/microsome assay. Mutation Research, 119:21?25.
・Bos RP, Hulshof CTJ, Theuws JLG, Henderson PT (1984b) Genotoxic exposure of workers creosoting wood. British Journal of Industrial Medicine, 41: 260-262.
・Bos RP, Jongeneelen FJ, Theuws JLG, Henderson PT (1984c) Exposure to mutagenic aromatic hydrocarbons of workers creosoting wood. IARC Scientific Publications, 59:279?288.
・Bos RP, Jongeneelen FJ, Theuws JLG, Henderson PT (1985) Detection of volatile mutagens in creosote and coal tar. Mutation Research, 156: 195-198.
・Brooks L, Hughes T, Claxton L, Austern B, Brenner R, Kremer F (1998) Bioassay-directed fractionation and chemical identification of mutagens in bioremediated soils. Environmental Health Perspectives, 106(Suppl. 6): 1435-1440.
・Chadwick R, George S, Kohan M, Williams R, Allison J, Talley D, Hayes Y, Chang J (1995) Potentiation of 2,6-dinitrotoluene genotoxicity in Fischer 344 rats by pretreatment with coal tar creosote. Journal of Toxicology and Environmental Health, 44: 319-336.
・Donnelly K, Brown K, Kampbell D (1987) Chemical and biological characterization of hazardous industrial waste: I. Prokaryotic bioassays and chemical analysis of a wood-preserving bottom-sediment waste. Mutation Research, 180(1): 31-42.
・Gagne F, Trottier S, Blaise C, Sproull J, Ernst B (1995) Genotoxicity of sediment extracts obtained in the vicinity of a creosote-treated wharf to rainbow trout hepatocytes. Toxicology Letters, 78: 175-182.

・Hughes T, Claxton L, Brooks L, Warren S, Brenner R, Kremer F (1998) Genotoxicity of bioremediated soils from the Reilly tar site, St. Louis Park, Minnesota. Environmental Health Perspectives, 106(Suppl. 6): 1427-1433.
・IPCS (1998) Selected non-heterocyclic polycyclic aromatic hydrocarbons. Geneva, World Health Organization, International Programme on Chemical Safety, 883 pp. (Environmental Health Criteria 202
・IUCLID (2000) Creosote ? CAS-No. 8001-58-9, ECB ? Existing Chemicals. Brussels, European Commission, Joint Research Centre, International Uniform Chemical Information Database, pp. 1-15 (IUCLID Data Sheet).

・Nylund L, Heikkila P, Hameila M, Pyy L, Linnainmaa K, Sorsa M (1992) Genotoxic effects and chemical compositions of four creosotes. Mutation Research, 265: 223-236.
・Simmon VF, Poole DC (1978) In vitro microbiological mutagenicity assays of creosote P1 and P2. Report prepared by SRI International for US Environmental Protection Agency (Contract No. 68-01-2458). Cited in Federal Register, 43(202): 48154-48214 [cited in IARC, 1985].
Sundstrom G, Larsson A, Tarkpea M (1986) Creosote. In: Hutzinger O, ed. Environmental chemistry. Vol. 3, Part D: Anthropogenic compounds. Berlin, Springer-Verlag, pp. 159-205.
・Zemanek M, Pollard S, Kenefick S, Hrudey S (1997) Toxicity and mutagenicity of component classes of oils isolated from soils at petroleum- and creosote-contaminated sites. Journal of the Air & Waste Management Association, 47(12): 1250-1258.

 
Cobalt (II) acetate tetrahydrate
  
  6147-53-1  Industry     249.08
AM Sal./E. coli Min ( 39.5 μg/plate, -S9); spa=2.5 x 103
1)
CA CHL/IU Min ( 0.01mg/ml, -S9), 24h; D20= 0.0092; TR= 2200
2)
1) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chemi. Subst., JETOC (Ed.), Suppl. 3, pp. 127 (2005)  (Tables in English)
2) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chemi. Subst., JETOC (Ed.), Suppl. 3, pp. 228 (2005)  (Tables in English)

Cobalt (II) sulfate (5 hydrate) (硫酸コバルト 5水化物)
   
 7758-99-8  MW: 249.68
AM Sal./E. coli Max (5.0 mg/plate, ±S9)
1)
1) Ministry of Labor, Japan; Mutagen. Test Data of Exist. Chemi. Subst., JETOC (Ed.) (1996)  (Tables in English)

Cobalt (II) sulfate (7 hydrate)(硫酸コバルト 7水化物)
   
 10124-43-3  MW: 281.12
AM Sal/E. coli Min (5.0 mg/plate, -S9); Spa= 22.4
○w
1)
1) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chemi. Subst., JETOC (Ed.) (1996)  (Tables in English)

Cocaine-HCl 
(コカイン・塩酸)
   
53-21-4  Medicine  339.82
AM Sal./E. coli Max (?)
1)
CA CHL/IU Min (1.0 mg/ml, -S9), 48h; D20= 1.0; TR= 140
2)
1) Natl Inst. Hygien. Sci., Tokyo ?
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998)  (Tables in English)

Coccoil-L-arginine ethyl ester
    Lavoratory  339.82
CA CHL/IU Max ( 0.125 mg/ml, -S9), 24-48h
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998)  (Tables in English)

● Cochineal
 (コチニール) 
  
 1343-78-8  Food/Natural
AM Sal. Min (100 mg/plate)
1)
CA CHL/IU Max ( 6.0 mg/ml, -S9), 24h; (No data for +S9)
2)
MNv Mice Max (?) 3)
1) Ishidate MJr., et al., Mutagens & Toxicity: Science Forum., Vol. 4, (No.5 ) (1981) (in Japanese)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998)  (Tables in English)
3) Ishidate MJr., et al., Toxicol. Forum., 10, 649-654 (1987)

● Cocoa extract
 (ココア抽出物)
    
  Food/Natural
CA CHL/IU Max ( 5.0mg/ml, ±S9), 24-48h
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998)  (Tables in English)

Cocoa pigment (A) 
(ココア色素)
     
Food/Natural
CA CHL/IU Min ( 1.0mg/ml, -S9), 24h
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test in vitro, LIC, Tokyo (1998)  (Tables in English)

Codeine phosphate (コデイン・燐酸)

  
52-28-8  Medicine   397.36
AM Sal. Max (?)
1)
CA CHL/IU Max ( 0.25 mg/ml, -S9), 24-48h (No data for +S9)
2)
MNv Mice Max (?) 3)
1) Natl Inst. Hygien. Sci., Tokyo ?
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998)  (Tables in English)
3) (?
)

● Colcemid  
(コルセミド)
 
  477-30-3  Laboratory  371.43
AM Sal. Max (?)
1)
CA CHL/IU Min ( 0.05 μg/ml, -S9), 24h (No data for +S9)
Poly ( D
20= 0.02 mg/ml)
2)
MNv ICR mice Min ( 10 mg/kg, ip) 3)
1) Natl Inst. Hygien. Sci., Tokyo, (?)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998)  (Tables in English)
3) Maier, P & Schumid W., Mutation Res., 40, 325-338 (1976)

● Copper chlorophyll
(銅クロロフィル)
  
 24111-17-9     Food  948.76
AM Sal Max ( 10 mg/plate, ±S9)
1, 2)
CA CHL/IU Max (  0.3 mg/ml, -S9), 24-48h (No data for +S9)
3)
1) Ishidate MJr., et al., Mutagen. & Toxicol., Vol. 12, 82-90 (1980) (in Japanese)
2) Ishidate MJr. (Ed.), Data Book of Mutagenicity Tests on Chemicals in Bacteria, LIC/Tokyo (1991)
 (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test i In Vitro, LIC, Tokyo (1998)  (Tables in English)
Top Page (トップページ)
Abbreviation  (省略記号) 
Mutagenicity  (変異原性)
Test Systems (試験法の種類)
Technical Problems (技術的問題点)
List of Compounds(化合物リスト)
Evaluation of Results (試験結果の評価)