Table E.4.
Genotoxicity (in vitro)
| Chemical name [FL‐no] | Test system | Test object | Concentration | Result | Reference | Comments |
|---|---|---|---|---|---|---|
| (Acetone [07.050]) | Rec assay | B. subtilis | NR | Negativea | Kawachi et al. (1980) | f |
| Rec assay | B. subtilis | NR | Negative | Ishizaki et al. (1979) | f | |
| Ames test | S. Typhimurium TA100 | 0.1–1,000 μg/plate | Negative | Rapson et al. (1980) | f | |
| Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537 | 174 μg/plate | Negativea | Florin et al. (1980) | f | |
| Ames test | S. Typhimurium TA98, TA100 | NR | Negativea | Kawachi et al. (1980) | f | |
| Ames testb | S. Typhimurium TA98, TA100 | 30 μL/plate | Negativec | Yamaguchi (1985) | f | |
| Ames test | S. Typhimurium TA97, TA98, TA100, TA1535, TA1537 | Up to 10,000 μg/plate | Negativea | McCann et al. (1975) | f | |
| Ames testb | S. Typhimurium TA97, TA98, TA100, TA1535, TA1537 | Up to 10,000 μg/plate | Negativea | Zeiger et al. (1992) | f | |
| Ames test | S. Typhimurium TA100 | 500 μg/plate | Negativea | Yamaguchi (1982) | f | |
| Ames test | S. Typhimurium TA97, TA98, TA100 | 20–40 μg | Negativea | Azizan and Blevins (1995) | f | |
| Sister chromatid exchange | Human embryo fibroblasts | NR | Negativec | Kawachi et al. (1980) | f | |
| Sister chromatid exchange | Hamster lung fibroblasts | NR | Negativec | Kawachi et al. (1980) | f | |
| Sister chromatid exchange | Chinese hamster ovary cells | Up to 10 μg/mL | Negative | Sasaki et al. (1980) | f | |
| Sister chromatid exchange | Chinese hamster ovary cells | Up to 5,020 μg/mL | Negativea | Loveday et al. (1990) | f | |
| Sister chromatid exchange | Diploid human fibroblasts | 5 μg/mL | Negative | Sasaki et al. (1980) | f | |
| Sister chromatid exchange | Human lymphocytes | 395 μg/mL | Negative | Norppa et al. (1983) | f | |
| Sister chromatid exchange | Human lymphocytes | 0.1–1 mM | Negative | Zarani et al. (1999) | f | |
| Chromosomal aberrations | Chinese hamster ovary cells | Up to 5,020 μg/mL | Negativea | Loveday et al. (1990) | f | |
| Chromosomal aberrations | Hamster lung fibroblasts | NR | Positivec | Kawachi et al. (1980) | f | |
| Aneuploidy induction | S. cerevisiae | 6.98–7.83% | Positivec | Zimmermann et al. (1985) | i | |
| (Isopropyl alcohol [02.079]) | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537 | 174 μg/plate | Negativea | Florin et al. (1980) | f |
| Ames testb | S. Typhimurium TA98, TA100, TA1535, TA1537, E. coli WP2uvrA | 5–5,000 μg/plate | Negativea | Shimizu et al. (1985) | f | |
| Ames testb | S. Typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 | Up to 10 mg/plate5 | Negativea | Zeiger et al. (1992) | f | |
| Forward mutation | Chinese hamster ovary cellsd | 0.5–5.0 mg/mL | Negativea | CMA (1990) | f | |
| Forward mutation | Chinese hamster ovary cellsd | 0.5–5.0 mg/mL | Negativea | Kapp et al. (1993) | f | |
| (2‐Butanone [07.053]) | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 10,000 μg/plate | Negativea | Douglas et al. (1980) | f |
| Ames test | S. Typhimurium TA102, TA104 | 1 mg/plate | Negative | Marnett et al. (1985) | f | |
| (2‐Butanone [07.053]) continued | Ames testb | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 5–5,000 μg/plate | Negativea | Shimizu et al. (1985) | f |
| Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 0.04–26 μg/plate | Negativea | O'Donoghue et al. (1988) | f | |
| Ames testb | S. Typhimurium TA97, TA98, TA100, TA104, TA1535, TA1537 | Up to 10,000 μg/plate | Negativea 1 | Zeiger et al. (1992) | f | |
| Ames test | S. Typhimurium TA102 | 5,000 μg/plate | Negativec | Müller et al. (1993) | f | |
| Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538, E. coli WP2uvrA | 4,000 μg/plate | Negative | Brooks et al. (1988) | f | |
| Gene conversion | S. cerevisiae | 5 mg/mL | Negativea | Brooks et al. (1988) | f | |
| Forward Mutation | L5178Y/TL+/− mouse lymphoma cells | 0.67–12 μg/mL | Negativea | O'Donoghue et al. (1988) | f | |
| Unscheduled DNA synthesis | Human lymphocytes | 0.72 mg/mL | Negativea | Perocco et al. (1983) | f | |
| Unscheduled DNA synthesis | Rat hepatocytes | 7.2–360 mg/mL | Negative | O'Donoghue et al. (1988) | f | |
| Chromosomal aberrations | Rat hepatocytes | 1,000 μg/mL | Negative | Brooks et al. (1988) | f | |
| Chromosomal aberrations | Chinese hamster ovary cells | 1,000 μg/mL | Negativea | Brooks et al. (1988) | f | |
| Cell transformation assaya | BALB/3T3 cells (clone A31‐1) | 6–18 μL/mL | Negative | O'Donoghue et al. (1988) | ||
| Aneuploidy induction | S. cerevisiae | 3.38% | Positivec | Zimmermann et al. (1985) | i | |
| Pentan‐3‐one [07.084] | Aneuploidy induction | S. cerevisiae | 1.48% | Positivec | Zimmermann et al. (1985) | i |
| Pentan‐3‐ol [02.077] | Chromosomal aberrations | Chinese hamster ovary cells | 0.5–10% | Negativea | Abbondandolo et al. (1980) | |
| Forward mutation | S. pombe | 0.5–10% | Negativea | Abbondandolo et al. (1980) | ||
| (2‐Heptanone [07.002]) | Unscheduled DNA synthesis | Rat hepatocytes | 1,000 ppm | Negative | Barber et al. (1999) | |
| Methyl‐3‐butan‐2‐one [07.178] | Aneuploidy induction | S. cerevisiae | 1.23–1.36% | Negativec | Zimmermann et al. (1985) | i |
| Aneuploidy induction | S. cerevisiae | 0.84–1.23% | Negativec | Zimmermann et al. (1985) | i | |
| (4‐Methyl‐2‐pentanone [07.017]) | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 0.03–3 mg/plate | Negativea | O'Donoghue et al. (1988) | f |
| Ames testb | S. Typhimurium TA97, TA98, TA100, TA1535 | Up to 6,667 μg/plate | Negativea | Zeiger et al. (1992) | f | |
| Ames test | E. coli WP2uvrA | 8,000 μg/plate | Negativec | Brooks et al. (1988) | f | |
| Gene conversion | S. cerevisiae | 5 mg/mL | Negativea | Brooks et al. (1988) | f | |
| Forward mutation | L5178Y/TL+/– mouse lymphoma cells | 0.26–4.2 μg/mL | Negativea | O'Donoghue et al. (1988) | f | |
| Unscheduled DNA synthesis | Rat hepatocytes | 8–80 μg/mL | Negative | O'Donoghue et al. (1988) | f | |
| Chromosomal aberrations | Rat hepatocytes | 1,000 μg/mL | Negative | Brooks et al. (1988) | f | |
| Cell transformation assaya | BALB/3T3 cells (clone A31‐1) | 1–7 μL/mL | Negative | O'Donoghue et al. (1988) | ||
| Chromosomal aberrations | Chinese hamster ovary cells | 1,000 μg/mL | Negativea | Brooks et al. (1988) | f | |
| Methyl‐4‐pentan‐2‐ol [02.183] | Ames testb | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538, E. coli WP2uvrA | 5,000 μg | Negativea | Shimizu et al. (1985) | |
| Methyl‐6‐heptan‐2‐one [07.181] | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537 | 5,000 μg/plate | Negativea | BASF (1989a) | |
| (2,6‐Dimethyl‐4‐heptanone [07.122]) | Ames testb | S. Typhimurium TA98, TA100, TA1535, TA1537 | 1–333 μg/plate | Negativea | Mortelmans et al. (1986) | f |
| Trimethyl‐6,10,14‐pentadecan‐2‐one [07.205] | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537 | 5,000 μg/plate | Negativea | BASF (1989b) | |
| (6‐Methyl‐5‐hepten‐2‐one [07.015]) | Reverse mutation | S. Typhimurium TA98, TA100, TA1535, TA1537 | 380 μg/plate | Negativea | (Florin et al. 1980) | g |
| (Isopropyl acetate [09.003]) | Ames testb | S. Typhimurium TA97, TA98, TA100, TA1537, TA1538 | Up to 10 mg/plate | Negativea | Zeiger et al. (1992) | f |
| (Isopropyl myristate [09.105]) | Ames teste | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 50 μg/plate | Negativea | Blevins and Taylor (1982) | f |
| Isopropyl hexadecanoate [09.606] | Ames teste | S. Typhimurium TA98, TA100, TA1535, TA1537, TA1538 | 50 μg/plate | Negativea | Blevins and Taylor (1982) | |
| 9‐Decen‐2‐one [07.262] | Ames testh | S. Typhimurium TA98, TA100, TA1535, TA1537 | Up to 5 μL/plate | Negativea | Flavour Industry (2009) | |
| Ames testh | E. coli WP2 (pKM 101) | Up to 5 μL/plate | Negativea | Flavour Industry (2009) | ||
| (6‐Methylhepta‐3,5‐dien‐2‐one [07.099]) | Reverse mutation | S. Typhimurium TA98, TA100, TA1535, TA1537 | 370 μg/plate | Negativea | Florin et al. (1980) | |
| Reverse Mutation | S. Typhimurium TA98, TA100, TA1535, TA1537, TA 102 | 1.6, 8, 40, 200, 1,000 and 5,000 μg/plate | Negativea | Williams (2009) | Toxicity observed in all strains at 2,000 μg/plate or greater in the absence of S9 and at 800 μg/plate in the presence of S9. Study design complied with current recommendations. Acceptable top concentration was achieved | |
| Micronucleus induction | Human peripheral blood lymphocytes | 225, 325 and 450 μg/mLk 225, 300 and 350 μg/mLl | Negative | Whitwell (2010) | Complies with draft OECD guideline 487. Acceptable levels of cytotoxicity achieved at the top concentrations used in all parts of the study | |
| Pseudo‐ionone [07.198] | Ames test | S. Typhimurium TA98, TA100, TA1535, TA1537 | 20.48, 51.2, 128, 320, 800, 2000 and 5,000 μg/plate j | Negativea | Florin et al. (1980) | |
| Reverse Mutation | S. Typhimurium TA98, TA100, TA1535, TA1537, TA 102 | 0.128, 0.64, 3.2, 16, 80, 400 and 2,000 μg/plate | Negativea | (Beevers, 2009) | Toxicity was observed in all strains at 400 μg/plate and greater in the presence and absence of S9 in this experiment | |
| 0, 12.5, 25, 50, 100, 200 and 400 μg/platej | Negativea | Precipitation was observed in the 400 μg/plate concentration in the presence and absence of S9 in this experiment. Study design complies with current recommendations. Acceptable top concentrations were achieved | ||||
| Micronucleus induction | Human peripheral blood lymphocytes | 30, 50 and 60 μg/mLk; 100, 110 and 120 μg/mLl | Negative | Lloyd (2010) | Complies with draft OECD guideline 487. Acceptable levels of cytotoxicity achieved at the top concentrations used in all parts of the study | |
| Micronucleus induction | Human peripheral blood lymphocytes | 10, 15 and 20 μg/mLm | Negative | Lloyd (2010) | Complies with draft OECD guideline 487. Acceptable levels of cytotoxicity achieved at the top concentrations used in all parts of the study |
FL‐no: FLAVIS number.
a
Assay performed with and without metabolic activation.
b
Modified Ames (pre‐incubation) protocol.
Assay performed with S9 metabolic activation.
c
Assay performed without S9 metabolic activation.
Maximum non‐toxic dose.
d
HGPRT locus.
e
Spot test.
f
Summarised by JECFA, 51st meeting (JECFA, 1999a).
g
Summarised by JECFA 59th meeting (JECFA, 2003).
h
Direct incorporation method.
i
Unusual experimental protocol for detection of aneuploidy, which can be considered a threshold effect not mediated by a direct interaction with DNA. Positive results were obtained at concentrations approaching cytotoxic levels and are very likely due to the presence of technical artefacts (low temperature treatment inducing tubulin dissociation). Indeed, absence of effect was recorded when the ice treatment was skipped. – The limited relevance of fungal systems together with the uncertain quality of these results make questionable their extrapolation to the in vivo situation in humans.
j
Assay modified with pre‐incubation in the presence of S9.
k
Without metabolic activation, 3 h treatment + 21 h recovery.
l
With metabolic activation, 3 h treatment + 21 h recovery.
m
Without metabolic activation, 24 h + 0 h recovery.