2,3-epoxypropyltrimethylammonium chloride

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro

Remarks:

Type of genotoxicity: other: summary of differents in vitro studies

Type of information:

other: EU Risk Assessment report

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Although the EU risk assessment report is secondary literature, all data and risk assessment for the human, health and the environment have been evaluated and reviewed by Finland prior to publication. The risk assessment report has been submitted to final approval and published in the Official Journal of the European Union C157/10 dated on 21.06.2008. Thus, it is considered the information reported are reliable with the restrictions that reliability of the data presented has not been assessed again.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

European Union Risk Assessment 2,3-epoxypropyltrimethylammonium chloride CAS RN 3033-77-0 Einecs No: 221-221-0

Author:

EC

Year:

2008

Bibliographic source:

Risk Assessment. Final approved version. Rapporteur: Finland (FIN). European communities. Printed in Italy. 147pp

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropyltrimethylammonium chloride

EC Number:

221-221-0

EC Name:

2,3-epoxypropyltrimethylammonium chloride

Cas Number:

3033-77-0

Molecular formula:

C6H14NO.Cl

IUPAC Name:

N,N,N-trimethyl(oxiran-2-yl)methanaminium chloride

Results and discussion

Any other information on results incl. tables

Table 7.6.1/1 Microbial mutagenicity tests with EPTAC.

Test system	Concentrations (vehicle in parenthesis)	Lowest effective dose, (S9 in parenthesis)	Result	Reference
S. typhimuriumTA 1538	0.2, 2, 20, 100, 500, 2000 μg/plate +/- S9 (aq.)	n/a	negative	(Dean et al., 1978), (Dean et al., 1985)
S. typhimuriumTA 1535, 1537, 1538, 98, 100, rfa-, uvrB- (reverse mutation)	0, 1.58, 5, 15.8,50, 158, 500, 1580, 5000μg/plate +/- S9 (aq.)	n/a	Positive	(Degussa, 1984)
S. typhimuriumTA 100, 1535, 1537, 97, 98	0, 5, 10, 10, 50, 100 μg/plate, +/- S9 (aq.)	5μg/plate (5μg/plate)	TA100 and 1535 positive at all concentrations with and without S9, (dose dependent)	(Vleminckx et al., 1987), (von der Hude et al., 1990b)
S. typhimuriumTA 1535, 1537, 1538, 98, 100	0, 2, 10, 50, 250, 1250, 6250μg/plate, +/- S9 (DMSO)	50μg/plate (250 μg/plate)	TA 1535, 1537 (dose dependent) and 100 (two highest doses) and with and without S9 positive (Doses not cytotoxic)	(Toxicol Laboratories, 1982)
Klebsiella pneumoniae (Luria Delbrück fluctuation test)	0 , 2, 5, 10 mmol/l +/- S9 (DMSO)	2 mmol/l (S9 n/a)	Mutation rate incr. with increasing conc: 0, 0, 2.6, 4.4, 7.4	(Voogd et al., 1981)
E. coli WP2, E. Coli WP2 uvrA, S. typhimurium, S. cerevisiae	0, 2, 20, 100, 500, 2000 μg/plate +/- S9 (aq.)	20μg/plate (uvrA), (20 μg/plate (uvrA))	Positive in both strains of E. Coliwith and without S9	(Dean et al., 1978), (Dean et al., 1985)
E. coli PQ37 SOS chromotest	0, 3.3, 10.0, 100.0 mmol/l, +/- S9 (aq.)	SOS inducing potency ~0.5	Positive	(von der Hude et al., 1990b)
S. cerevisiae JD1 induction of gene conversion (trp & his locus)	0, 0.1, 0.5, 1.0, 5.0, 10.0 μg/ml for 1h @ 37 °C + 16h @ 29°C, +/- S9 (aq.)	0.5 mg/ml (his), (0.5 mg/ml), 1 mg/ml (trp), (1 mg/ml)	Positive with and without S9	(Dean et al., 1978), (Dean et al., 1985)
S. cerevisiaeD7 induction of gene	0, 0.01, 0.05, 0.10, 0.50, 1.00, 5.00 mg/ml for 1h	0.5 mg/ml (0.5 mg/ml)	Positive: Gene conversion increased	(Vleminckx et al., 1987)

Table 7.6.1/2 Mutagenicity tests with EPTAC in mammalian cells in vitro

Test system	Concentrations	Result	Reference
PRIMARY RAT HEPATOCYTE UDS	0, 2, 20, 200 μMOL/L, FOR 20H @ 37 °C	POSITIVE CELL COUNT VARIED FROM 15 TO 100 % IN THE TREATED CELLS. AT 20μMOL EPTAC WAS UDS POSITIVE (>50% POS. CELLS + NET GRAIN COUNT HIGHER THAN 2X SD OF CONTROL)	(von der Hude et al., 1990a)
CHINESE HAMSTER OVARY (CHO) CELLS	0, 5, 10, 20, 50 AND 100 μG/ML OF EPTAC FOR 18 HOURS	FREQUENCY OF ABERRATIONS, WITH OR WITHOUT GAPS, PER CELL AND THE PERCENTAGE OF CELLS WITH ALL ABERRATIONS INCREASED WITH THE DOSE	(Vleminckx et al., 1987)
SCE IN CHINESE HAMSTER V79	0, 0.125, 0.25, 0,5, 1.0, 2.0 MMOL/L	POSITIVE STARTING FROM 0.25 MMOL/L, DOSE DEPENDENT INCREASE, R=0.87, S=7.1	(von der Hude et al., 1991)
CHROMOSOME ASSAY IN RL1 CELL LINE	0, 10, 0, 40, 80 μG/ML	POSITIVE: DOSE RELATED INCREASE OF CHROMATID GAPS	(Dean et al., 1978), (Dean et al., 1985)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

Based on the several in vitro genotoxicity studies performed, it could be conclude that EPTAC is a mutagen according to the criteria of the Annex I
of the CLP Regulation (EC) N° 1272/2008.

Executive summary:

EPTAC causes mutations in E. coli WP2 and S. typhimurium 1535, 1537 and 100 but not in 1538 or 98. These mutations did not require metabolic activation to occur. The evidence from the bacterial mutagenicity tests suggests that EPTAC acts as a direct point mutagen by base pair substitution but not frame shift mutation. In addition, tests in two yeast strains have demonstrated that EPTAC can cause gene conversion in two different gene loci.

The positive response in the liver UDS test gives indications of increased DNA damage in mammalian cells as well.

In addition, a well-correlated dose-related increase of sister chromatid exchanges in the Chinese hamster V79 cells was seen.

Damage to chromosomes has been shown to occur in mammalian test systems in vitro. The results of the in vitro chromosome aberration tests in both rat liver cells and Hamster ovary cells showed that both the frequency of aberrations per cell, with or without gaps, and the percentage of cells with all aberrations increased with the dose.

Positive in vitro results show that in addition to causing point mutations in bacterial systems, EPTAC has clastogenic or aneugenic potential in mammalian cells as well.