@@@@@@@@@@@@@@@@@@@@@@@@@@@
Group G-3 ‰»Šw\‘’@(Chemical Structure)  
œ Glycidol @(Glycide) @iƒOƒŠƒVƒh[ƒ‹j (2,3-Epoxy-1-propanol)
@@@CASF556-52-5 @Industry/stabilizer@@MW: 74.08
AM Sal. Min (?)(}S9)
›
1)
AM Sal./E. coli Min ( 1.22 ƒΚg/plate, }S9); spa= 2 x 104(TA1535)  9)
YM S. cerevisiae
iy•κ‹Ϋj
Min (?)(-S9)
›
2)
MB S. Bombe (ŒΓΆŽq”X‹Ϋj Min (?)(-S9)
›
3)
MB N. crossa
iƒAƒJƒpƒ“ƒJƒrj
Min (?)(-S9)
›
4)
MLA L-5178Y Min (?)(-S9)
›
1, 5)
UDS Human W138 Min (?)(-S9)
›
5)
CA CHO Min (?)(-S9)
›
1)
CA CHL/IU Min (0.08 mg/ml, -S9), 24h; D20= 0.055;  TR= 700  8)
CA Human LY Min (?)(-S9)
›
6)
SCE CHO Min (?)(-S9)
›
1)
UDS Human LY Min (?)(-S9)
›
6)
SLRL Drosophila Min (?)(fed)
›
1)
RTv Drosophila Min (?)(fed)
›
1)
CAv Mice/BM Min (?)(ip)@
›
1)
CAv Rats/BM Min (?)(ip)@
›
7)
1) NTP Technical Report No. 374, DHHS (NIH) Pub. No. 90-2829, NIEHS, USA
2) Izard G: C.R. Acad. Sci., D276: 3037-3040 (1973)
3) Migliore L, et al,: Mutation Res. 102, 425-437 (1982)
4) Kolmark G & Giles NH: Genetics, 40, 890-902 (1955)
5) Thompson ED, et al,: Mutation Res., 90, 213-231 (1981)
6) Norppa H, et al,: Mutation Res., 91, 243-250 (1981)
7) Thompson ED & Gibson DP: Fd. Chem. toxicol., 22, 665-676 (1984)
8) Ministry of Labour, Japan, Mutagenicity Test Data on Exixt. Chem. Subst., JETOC(Ed.), pp. 422 (1996) (Tables in English)
9) Ministry of Labour, Japan, Mutagenicity Test Data on Exixt. Chem. Subst., JETOC(Ed.), Suppl., 3, pp.179  (2005)) (Tables in English)


 US-NTP Genotoxicity Screening:
› Ames Test:
›
› MLA:
›
› CA /SCE with CHO:
›
› SLRL/RTv: with Drosophila:
›

œ Glycidyl phenyl ether iƒOƒŠƒVƒWƒ‹ƒtƒFƒjƒ‹ƒG[ƒeƒ‹j
@
@ @122-60-1 @Industry @ 150.18
CA CHL/IU Min ( 0.02 mg/ml, -S9), 24h@D20=0.022; TR=400
›
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycine (crystal)
@
@@ 56-40-6@@Food @@ 75.07
AM Sal. Max ( 35 mg/plate, }S9)
 
1, 2)
CA CHL/IU Max ( 1.0 mg/ml, -S9), 24, 48h (No data for +S9)
 
2, 3)
1) Ishidate MJr(Ed): Data Book for Mutagenicity in Bacteria, LIC (1991) (Tables in English)
2) Ishidate MJr et al, Mutagens & Toxicity, 5, 579-587 (1982) (in Japanese)
3)
Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glyclopyramide iƒOƒŠƒNƒƒsƒ‰ƒ~ƒhj
@@@
631-27-6 @ Medicine @ 295.71
CA CHL/IU Max ( 2.0 mg/ml, -S9), 24, 48h @(No data for +S9)
 
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycocyamine iƒOƒŠƒRƒTƒCƒAƒ~ƒ“j
@@@ 352-97-6 @117.11
CA CHL/IU Max ( 4.0 mg/ml, -S9j,24, 48h(No data for +S9);
D20=0.41; TR=10
 
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycodiazine iƒOƒŠƒRƒ_ƒCƒAƒWƒ“j
@@
339-44-6 @Medicine @ 309.35
CA CHL/IU Min ( 8.0 mg/ml, -S9), 24, 48h@(No data for +S9)
›w
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycol-ether diamine tetraacetic acid
@@@
67-42-5 @@Laboratory@@ 380.35
CA CHL/IU Max ( 2.0 mg/ml, -S9), 24, 48h@(No data for +S9)
 
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycyrrhiza pigment
@@@
Food/Natural@
CA CHL/IU Max ( 0.25 mg/ml, -S9j, 24, 48h@(No data for +S9);
D
20=0.87; TR=2.0
 
1)
1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glycyrrhizin @(Liquorice) iƒOƒŠƒNƒŠƒŠƒ`ƒ“j
@@@
1405-86-3@@Food@@ 822.94
AM Sal. Max ( 10 mg/plate, }S9)
 
1)
CA CHL/IU Min ( 4.0 mg/ml, -S9j, 24, 48h D20= 6.8; TR= 0.35;
No data for +S9)
›w
2)
1) IshidateMJr (Ed): Data Book for Mutagenicity Tests on Chemicals in Bacteria, LIC (1991) (Tables in English)
2)@
Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro LIC, Tokyo (1998) (Tables in English)

œ Glyoxal  (Diformyl) iƒOƒŠƒIƒLƒT[ƒ‹; ƒGƒ^ƒ“ƒWƒA[ƒ‹G@ƒVƒ…ƒEŽ_ƒWƒAƒ‹ƒfƒqƒhG@ƒWƒzƒ‹ƒ~ƒ“j
@@@
107-22-2@@Industry@@ 58.04
AM Sal./E. coli Min ( 40 ƒΚg/plate, }S9)Gspa= 8500 (TA100)
›
1)
AM Sal. Min ( 500 ƒΚg/plate, }S9) › 2)
AM Sal. Min ( 10 mg/plate, }S9) › 3)
AM Sal. Min (127 ƒΚg/plate, }S9) › 4)
AM E. coli Min ( 400 ƒΚg/plate, }S9) › 5)
AM Sal. Min ( 100 ƒΚg/plate, }S9) › 6)
AM E. coli Min (?), }S9 › 7)
MLA L5178Y Min ( 61.5ƒΚg/ml -S9) › 8)
CA V79 Min ( 400 ƒΚg/ml, -S9) › 9)
CA CHO/Hum. lym. Min ( 100 ƒΚg/ml, -S9) › 10)
UM Sal. Min ( 100 ƒΚg/ml, }S9) › 11)
SOS E. coli Min ( 348 ƒΚg/ml, -S9) › 12)
REC B. subtilis Min ( 30.3 ƒΚg/ml, }S9) › 13)
UDS TC-SV40 Min ( 5 x 10-5, -S9) › 14)
SLRLv Drosophila Max ( 40 ƒΚg/ml, ip)   15)
DLv Drosophila Max ( 40 ƒΚg/ml, ip )   15)
UDSv Rat stomach Min ( 400 mg/kg, or ), for 2h › 16, 17)
DNAv Rat stomach Min ( 550 mg/kg, or ), for 2h › 18)
1) Ministry of Labour, Japan, Mutagenicity Test Data on Exixt. Chem. Subst., JETOC(Ed.), (1996) (Tables in English)
2) Bjeldanes LF & Chew H., Mutarion Res., 67, 367-371 (1979)
3) Niemand JG., et al.., J. Agric. Food Chem., 31, 1016-1070 (1983)
4) Muller W., et al., Environ. Health Perspect., 103 (Suppl 3), 33-36 (1993)
5) Kamiya N., et al., Mutation Res., 377, 13-16 (1997)
6) Ueno H., et al., Fund Appl. Toxicol., 16, 763-772 (1991)
7) Kato F., et al., Mutation Res., 216, 316-367 (1989)
8) Wangenheim J & Bolesfoldi G., Mutagenesis, 3, 193-205 (1988)
9) Nishi Y., et al., Mutation Res., 227, 117-123 (1989)
10) Tucker JD., et al., Mutation Res., 224, 269-279 (1989)
11) Ono Y., et al.,  Water Sci. Tech., 23, 329-338 (1991)
12) von der Hude W., et al., Mutation Res., 203, 81-94 (1988)
13) Matsui S., et al., Water Sci., Tech., 21, 875-887 (1989)
14) Cornago P., et al., Biochemie, 71, 1205-1210 (1989)
15) Barnett BM. & Munoz ER., Mutation Res., 212, 173-179 (1989)
16) Furihata C., et al., Mutation Res., 213, 227-231 (1985)
17) Furihata C & Matsushima T., Environ. Mol. Mutagen., 14, 63 (1989)
18) Furihata C., et al., Mutation Res., 203, 371 (1988)

yNotez@(Cited from CICADs documents, 57, 2004)
   Glyoxal is directly genotoxic in vitro in bacterial and mammalian cells. In vivo tests show various findings. A detailed overview of genotoxicity tests in bacterial test systems is published in the source document (BUA, 1997).

   In the Salmonella microsomal assay, glyoxal (test substance 30-40% glyoxal) was a direct mutagen in strains TA 100, TA 102, TA 104, and TA 2638, with a weaker response in the presence of a metabolic activation system (BUA, 1997). A direct genotoxic activity of glyoxal was further evident in the L-arabinose resistance assay with S. typhimurium BA9 and BA13 (Ruiz-Rubio et al., 1985; Ariza et al., 1988) and in the SOS chromotest with E. coli PQ37 (von der Hude et al., 1988).

   Furthermore, DNA repair tests yielded positive responses in both the presence and absence of metabolic activation systems, as in the SOS umu-test with S. typhimurium TA 1535/pSK 1002 (Ono et al., 1991a,b), in the rec-assay with Bacillus subtilis (also with metabolic activation; Matsui et al., 1989), and in the differential DNA repair test with E. coli K-12/343/636 uvrB+/recA+ and K-12/343/591 uvrB-/recA- (Hellmer & Bolcsfoldi, 1992a). When the latter test was performed as a host-mediated assay in mice, with oral application of 570 or 1700 mg glyoxal/kg body weight and intravenous application of the bacteria, a genotoxic effect was not demonstrable in bacteria isolated from blood, liver, lungs, kidneys, or testicles (Hellmer & Bolcsfoldi, 1992b), which may be explained by the high reactivity of glyoxal ? for example, with proteins . In Saccharomyces cerevisiae D61.M, induction of mitotic recombinations pointed to reaction of glyoxal with DNA, whereas modification of proteins was indicated by chromosome losses (in the presence of propionitrile, which is a strong inducer of chromosomal malsegregation), suggesting interference of glyoxal with microtubular function (Zimmermann & Mohr, 1992).

   With E. coli WP2 uvrA, in both the absence and presence of metabolic activation, negative test results were found in the standard plate incorporation assay (Hoechst AG, 1984f), whereas an insufficiently documented preincubation assay reported positive test results (Kato et al., 1989). Ueno et al. (1991b) investigated the characteristics of mutagenicity by glyoxal (particularly a possible role of active oxygen species) in S. typhimurium TA 100 and TA 104. The scavengers of singlet oxygen almost completely suppressed the mutagenic action of glyoxal.

   A direct genotoxic action of glyoxal was established in a variety of tests with mammalian cells without metabolic activation (see BUA, 1997): in a mutagenicity test with mouse lymphoma cells (TK assay) (Wangenheim & Bolcsfoldi, 1988), in chromosomal aberration tests with Chinese hamster ovary (CHO) cells (NOTOX, 1986) and V79 cells (Nishi et al., 1989), and in tests for the induction of unscheduled DNA synthesis in TC-SV40 cells of Syrian hamster (Cornago et al., 1989), for the induction of sister chromatid exchanges in CHO cells and human lymphocytes, for the induction of endoreduplication in CHO cells (Tucker et al., 1989), and for the induction of DNA strand breaks in mouse lymphoma cells (Garberg et al., 1988). In primary rat hepatocytes, glyoxal induced DNA single strand breaks but no DNA cross-links (Ueno et al., 1991c).

   DNA damage was further demonstrated in the comet assay with TK6 human lymphoblastoid cells by the induction of concentration-dependent increases of tail moment and tail length (Henderson et al., 1998). Primary rat hepatocytes exposed to glyoxal at higher concentrations (0.5-10 mg/ml) produced different concentration-dependent types of DNA damage. Tail moment and the formation of comets with head and tail (indicative of DNA strand breakage) decreased with increasing glyoxal concentration, whereas circular DNA spots with highly condensed areas increasingly appeared at the mid- and high concentrations. Among 100 tested substances, this damage was shown to be specific for certain aldehydes and was attributed to their DNA cross-linking activity (Kuchenmeister et al., 1998). In cultures of human umbilical vein endothelial cells, addition of 100 ƒΚg glyoxal/ml caused a significant increase of formamidopyrimidine N-glycosylase (FPG)-sensitive sites (measured by the comet assay) in the absence of increased intracellular levels of hydroperoxides. FPG repairs oxidative DNA damage and abasic sites and further was supposed to repair guanine-glyoxal adducts (Shimoi et al., 2001).

   A significantly increased rate of sex-linked recessive lethals reported in Drosophila melanogaster in preliminary experiments (Mazar Barnett & Munoz, 1969) was not confirmed in later assays, showing the absence of any genotoxic effect in assays for sex-linked recessive lethals in mature sperm and in the earlier stages of spermatogenesis, as well as in assays for clastogenic activity in mature sperm (reciprocal translocation, dominant lethal, and chromosome loss). However, from the increase of radiation-induced clastogenic effects after pretreatment with glyoxal, it was concluded that glyoxal came in contact with the target cells. The possibility of detoxifying mechanisms for glyoxal or of an efficient repair of glyoxal-induced damage in Drosophila was discussed (Mazar Barnett & Munoz, 1989).

   No clastogenic activity was found in a micronucleus assay in mouse bone marrow (Societe Francaise Hoechst, 1986; no further data available).

   Glyoxal was demonstrated to be genotoxic at the site of application after administration by gastric intubation. In the pyloric mucosa of male Fischer 344 rats, both significantly increased unscheduled DNA synthesis and DNA single strand breaks were induced at dosages of 400-500 mg/kg body weight within 2 h. Cytotoxicity was not reported (Furihata et al., 1985, 1988, 1989; Furihata & Matsushima, 1989). In contrast, in rat hepatocytes, a test for unscheduled DNA synthesis was negative (CCR, 1992). Glyoxal has also been shown to cause DNA strand breaks in rat hepatocytes 2-9 h after a single oral exposure to 200-1000 mg glyoxal/kg body weight (Ueno et al., 1991b). Single strand breaks were also detected in livers of rats within 2 h following a single oral exposure at 200-1000 mg glyoxal/kg body weight. The frequency of breaks reached a maximum after 9 h of exposure. Hardly any DNA lesions were detected in other tissues following exposure to 1000 mg glyoxal/kg body weight. Glyoxal causes DNA single strand breaks in rat hepatocytes following in vitro and in vivo exposure (Ueno et al., 1991c).

   Cell transformation assays in C3H/10T? cells with three different commercial products of glyoxal (test concentrations from 0.0013 to 0.195 ƒΚl/ml) yielded negative test results (Mason 1980a,b,c).


References
EBUA (1997): German Chemical Society (GDCh) Advisory Committee on Existing Chemicals of Environmental Relevance (BUA). Stuttgart, S. Hirzel, Wissenschaftliche Verlagsgesellschaft, pp. 1-64 (BUA Report 187) (in German).
ERuiz-Rubio M, Alejandro-Duran E, Pueyo C (1985) Oxidative mutagens specific for A.T. base pairs induce forward mutations to L-arabinose resistance in Salmonella typhimurium. Mutation Research, 147:153-163.
EAriza RR, Dorado G, Barbancho M, Pueyo C (1988): Study of the cause of direct-acting mutagenicity in coffee and tea using the Ara test in Salmonella typhimurium. Mutation Research, 201:89-96.
Evon der Hude W, Behm C, Gurtler R, Basler A (1988) Evaluation of the SOS chromotest. Mutation Research, 203:81-94.

EOno Y, Somiya I, Kawamura M (1991a): The evaluation of genotoxicity using DNA repairing test for chemicals produced in chlorination and ozonation process. Water Science and Technology, 23:329-338.
EOno Y, Somiya I, Kawamura M (1991b) Genotoxicity of by-products in the chemical oxidation processes. Water Science and Technology, 14:633-641.
EMatsui S, Yamamoto R, Yamada H (1989): The Bacillussubtilis/ microsome rec-assay for the detection of DNA damaging substances which may occur in chlorinated and ozonated waters. Water Science and Technology, 21:875-887.
EHellmer L, Bolcsfoldi G (1992a) An evaluation of the E. coli K-12 uvrB/recA DNA repair host-mediated assay. I. In vitro sensitivity of the bacteria to 61 compounds. Mutation Research, 272:145-160.

EHellmer L, Bolcsfoldi G (1992b): An evaluation of the E. coli K-12 uvrB/recA DNA repair host-mediated assay. II. In vivo results for 36 compounds tested in the mouse. Mutation Research, 272:161-173.
EZimmermann F, Mohr A (1992): Formaldehyde, glyoxal, urethane, methyl carbamate, 2,3-butanedione, 2,3-hexanedione, ethyl acrylate, dibromoacetonitrile and 2-hydroxypropionitrile induce chromosome loss in Saccharomyces cerevisiae. Mutation Research 270:151-166
EKato F, Araki A, Nozaki K, Matsushima T (1989): Mutagenicity of aldehydes and diketones. Mutation Research, 216:366-367.
ENishi Y, Miyakawa Y, Kato K (1989) Chromosome aberrations induced by pyrolysates of carbohydrates in Chinese hamster V79 cells. Mutation Research, 227:117-123.

EHoechst AG (1984f): Ergebnis der abwasserbiologischen Untersuchungen: Glyoxal 40. Frankfurt, Hoechst AG, pp. 1-4 (W 84-087).
EWangenheim J, Bolcsfoldi G (1988): Mouse lymphoma L5178Y thymidine kinase locus assay of 50 compounds. Mutagenesis, 3(3):193-205.
ENOTOX (1986): Evaluation of the ability of SIS 503 to induce chromosome aberrations in cultured Chinese hamster ovary (CHO) cells. Prepared by NOTOX C.V., 's-Hertogenbosch, for Henkel KGaA, Dusseldorf (Unpublished Report No. 0367/EC 124) [cited in BUA, 1997].
ECornago P, Lopez Zumel M, Santos L, Pintado M (1989): Semiconservative and unscheduled DNA synthesis on mammalian cells and its modification by glyoxylic compounds. Biochimie, 71:1205-1210.
ETucker JD, Taylor RT, Christensen ML, Strout CL, Hanna ML, Carrano AV (1989): Cytogenetic response to 1,2-dicarbonyls and hydrogen peroxide in Chinese hamster ovary AUXB1 cells and human peripheral lymphocytes. Mutation Research, 224:269-279.
EGarberg P, Akerblom EL, Bolcsfoldi G (1988): Evaluation of a genotoxicity test measuring DNA-strand breaks in mouse lymphoma cells by alkaline unwinding and hydroxyapatite elution. Mutation Research 203:155-176.
EUeno H, Nakamuro K, Sayato Y, Okada S (1991b): Characteristics of mutagenesis by glyoxal in Salmonella typhimurium: contribution of singlet oxygen. Mutation Research, 251:99-107.
EUeno H, Nakamuro K, Sayato Y, Okada S (1991c): DNA lesion in rat hepatocytes induced by in vitro and in vivo exposure to glyoxal. Mutation Research, 260:115-119.
EHenderson L, Wolfreys A, Fedyk J, Bourner C, Windebank S (1998): The ability of the comet assay to discriminate between genotoxins and cytotoxins. Mutagenesis, 13(1):89-94.
EKuchenmeister F, Schmezer P, Engelhardt G (1998):  Genotoxic bifunctional aldehydes produce specific images in the comet assay. Mutation Research, 419(1-3):69-78.
EShimoi K, Okitsu A, Green MHL, Lower JE, Ohta T, Kaji K, Terato H, Ide H, Kinae N (2001):  Oxidate DNA damage by high glucose and its suppression in human umbilical vein endothelial cells. Mutation Research, 480:371-378.
EMazar Barnett B, Munoz ER (1969): Mutation test with glyoxal in Drosophila melanogaster males. Drosophila Information Service, 44:119.
EMazar Barnett B, Munoz ER (1989): Effect of glyoxal pretreatment on radiation-induced genetic damage in Drosophila melanogaster. Mutation Research, 212:173-179.
EFurihata C, Yoshida S, Matsushima T (1985): Potential initiating and promoting activities of diacetyl and glyoxal in rat stomach mucosa. Japanese Journal of Cancer Research, 76(9):809-814.
EFurihata C, Sato Y, Matsushima T (1988) Alkaline elution of DNA from stomach pyloric mucosa of rats treated with MNNG and glyoxal. Mutation Research, 203:371.
EFurihata C, Hatta A, Sato Y, Matsushima T (1989): Alkaline elution of DNA from stomach pyloric mucosa of rats treated with glyoxal. Mutation Research, 213:227-231.

EFurihata C, Matsushima T (1989): Prediction of possible carcinogens, tumor-promotors and anti-tumor promotors in the glandular stomach. Environmental and Molecular Mutagenesis, 14(15):63.
ECCR (1992): In vivo/in vitro unscheduled DNA synthesis in rat hepatocytes with glyoxal. Prepared by Cytotest Cell Research GmbH & Co. KG, Rosdorf, for the Employment Accident Insurance Fund of the German Chemical Industry (Unpublished Report CCR Project 230602) [cited in BUA, 1997].
EMason (1980a): C3H/ 10T1/ 2 cell transformation assay, Aerotex glyoxal 40. Prepared by EG & G Mason Research Institute, Rockville, MD, for the American Cyanamide Company (Unpublished Report No. 029-626-292-8) [cited in BUA, 1997].
EMason (1980b): C3H/ 10T1/ 2 cell transformation assay, European glyoxal 40. Prepared by EG & G Mason Research Institute, Rockville, MD, for the American Cyanamide Company (Unpublished Report No. 029-626-293-8) [cited in BUA, 1997].
EMason (1980c): C3H/ 10T1/ 2 cell transformation assay, American Hoechst Glyoxal 40. Prepared by EG & G Mason Research Institute, Rockville, MD, for the American Cyanamide Company (Unpublished Report No. 029-636-321-8) [cited in BUA, 1997].

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