Table 2.

Summary results of historically discordant nitrosamines tested (methanol).

Compound (CAS)MethodS9 Species (induction)VehicleStrain S typhimurium or E coli*Result
TA98TA100TA1537TA1535WP2*
Methyl(neopentyl)nitrosamine (CAS 31820-22-1)2PlateNoneMethanol−ive−ive−ive−ive+ivePositive
None3MethanolNTNTNTNT−iveNegative
None4MethanolNTNTNTNT−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
Bis(2-methoxyethyl)nitrosoamine (CAS 67856-65-9)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitroso-N-methyl-4-fluoroaniline (CAS 937-25-7)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol+ive−ive−ive−ive+ivePositive
HamsterMethanol+ive−ive−ive−ive−ivePositive
Dinitrosoethambutol, (R,R)-(CAS 52322-22-2)1PlateNoneMethanol−ive−ive−ive+ive−ivePositive
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive+ive−ivePositive
N-methyl-N-nitroso-2-propanamine (CAS 30533-08-5)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitrosodiisopropylamine (CAS 601-77-4)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
1-Cyclopentyl-4-nitrosopiperazine (CAS 61379-66-6)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRat (10%)Methanol−ive+ive−ive+ive−ivePositive
Hamster (10%)Methanol−ive+ive−ive+ive+ivePositive
Rat (30%)Methanol−ive+ive−ive+ive+ivePositive
Hamster (30%)Methanol−ive+ive−ive+ive+ivePositive
Mononitrosocaffeidine (CAS 145438-96-6, Batch: 170457)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
Compound (CAS)MethodS9 Species (induction)VehicleStrain S typhimurium or E coli*Result
TA98TA100TA1537TA1535WP2*
Methyl(neopentyl)nitrosamine (CAS 31820-22-1)2PlateNoneMethanol−ive−ive−ive−ive+ivePositive
None3MethanolNTNTNTNT−iveNegative
None4MethanolNTNTNTNT−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
Bis(2-methoxyethyl)nitrosoamine (CAS 67856-65-9)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitroso-N-methyl-4-fluoroaniline (CAS 937-25-7)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol+ive−ive−ive−ive+ivePositive
HamsterMethanol+ive−ive−ive−ive−ivePositive
Dinitrosoethambutol, (R,R)-(CAS 52322-22-2)1PlateNoneMethanol−ive−ive−ive+ive−ivePositive
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive+ive−ivePositive
N-methyl-N-nitroso-2-propanamine (CAS 30533-08-5)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitrosodiisopropylamine (CAS 601-77-4)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
1-Cyclopentyl-4-nitrosopiperazine (CAS 61379-66-6)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRat (10%)Methanol−ive+ive−ive+ive−ivePositive
Hamster (10%)Methanol−ive+ive−ive+ive+ivePositive
Rat (30%)Methanol−ive+ive−ive+ive+ivePositive
Hamster (30%)Methanol−ive+ive−ive+ive+ivePositive
Mononitrosocaffeidine (CAS 145438-96-6, Batch: 170457)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative

1The maximum concentration tested was 5000 μg/plate, the maximum concentration in accordance with current guidelines.

2The maximum concentrations analysed were limited by toxicity or to 5000 μg/plate (the maximum concentration in accordance with current guidelines) as appropriate in each strain, in the presence and absence of S9-mix.

3Test 2 to clarify result.

4Test 3 to confirm result.

NT—not tested.

n.b. SAR for all compounds is solely N-Nitro or N-Nitroso structure.

*E. coli strain WP2uvrA (pkM101).

Table 2.

Summary results of historically discordant nitrosamines tested (methanol).

Compound (CAS)MethodS9 Species (induction)VehicleStrain S typhimurium or E coli*Result
TA98TA100TA1537TA1535WP2*
Methyl(neopentyl)nitrosamine (CAS 31820-22-1)2PlateNoneMethanol−ive−ive−ive−ive+ivePositive
None3MethanolNTNTNTNT−iveNegative
None4MethanolNTNTNTNT−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
Bis(2-methoxyethyl)nitrosoamine (CAS 67856-65-9)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitroso-N-methyl-4-fluoroaniline (CAS 937-25-7)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol+ive−ive−ive−ive+ivePositive
HamsterMethanol+ive−ive−ive−ive−ivePositive
Dinitrosoethambutol, (R,R)-(CAS 52322-22-2)1PlateNoneMethanol−ive−ive−ive+ive−ivePositive
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive+ive−ivePositive
N-methyl-N-nitroso-2-propanamine (CAS 30533-08-5)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitrosodiisopropylamine (CAS 601-77-4)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
1-Cyclopentyl-4-nitrosopiperazine (CAS 61379-66-6)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRat (10%)Methanol−ive+ive−ive+ive−ivePositive
Hamster (10%)Methanol−ive+ive−ive+ive+ivePositive
Rat (30%)Methanol−ive+ive−ive+ive+ivePositive
Hamster (30%)Methanol−ive+ive−ive+ive+ivePositive
Mononitrosocaffeidine (CAS 145438-96-6, Batch: 170457)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
Compound (CAS)MethodS9 Species (induction)VehicleStrain S typhimurium or E coli*Result
TA98TA100TA1537TA1535WP2*
Methyl(neopentyl)nitrosamine (CAS 31820-22-1)2PlateNoneMethanol−ive−ive−ive−ive+ivePositive
None3MethanolNTNTNTNT−iveNegative
None4MethanolNTNTNTNT−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
Bis(2-methoxyethyl)nitrosoamine (CAS 67856-65-9)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitroso-N-methyl-4-fluoroaniline (CAS 937-25-7)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol+ive−ive−ive−ive+ivePositive
HamsterMethanol+ive−ive−ive−ive−ivePositive
Dinitrosoethambutol, (R,R)-(CAS 52322-22-2)1PlateNoneMethanol−ive−ive−ive+ive−ivePositive
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive+ive−ivePositive
N-methyl-N-nitroso-2-propanamine (CAS 30533-08-5)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive+ive−ive+ive−ivePositive
N-Nitrosodiisopropylamine (CAS 601-77-4)2PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative
1-Cyclopentyl-4-nitrosopiperazine (CAS 61379-66-6)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRat (10%)Methanol−ive+ive−ive+ive−ivePositive
Hamster (10%)Methanol−ive+ive−ive+ive+ivePositive
Rat (30%)Methanol−ive+ive−ive+ive+ivePositive
Hamster (30%)Methanol−ive+ive−ive+ive+ivePositive
Mononitrosocaffeidine (CAS 145438-96-6, Batch: 170457)1PlateNoneMethanol−ive−ive−ive−ive−iveNegative
Pre-IncRatMethanol−ive−ive−ive−ive−iveNegative
HamsterMethanol−ive−ive−ive−ive−iveNegative

1The maximum concentration tested was 5000 μg/plate, the maximum concentration in accordance with current guidelines.

2The maximum concentrations analysed were limited by toxicity or to 5000 μg/plate (the maximum concentration in accordance with current guidelines) as appropriate in each strain, in the presence and absence of S9-mix.

3Test 2 to clarify result.

4Test 3 to confirm result.

NT—not tested.

n.b. SAR for all compounds is solely N-Nitro or N-Nitroso structure.

*E. coli strain WP2uvrA (pkM101).

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