2,3-epoxypropyltrimethylammonium chloride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-10-15 to 1990-10-18

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to the appropriate OECD test guideline, with acceptable limitations, which were that only one dose was administered and only 1000 erythrocytes examined to determine the PCE/NCE ratio It was conducted in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1984

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

Quab 151, 88 %

Test animals

Species:

mouse

Strain:

other: BOR: NMRI (SPF Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Versuchtstierzucht GmbH &Co.KG., D-4799 Borchen
- Age at study initiation: 5 weeks
- Weight at study initiation: males 29-35 g, females 23-31 g
- Assigned to test groups randomly: yes
- Fasting period before study: 16 hours
- Housing: Macrolon cages, type II, 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: none given in report
- Concentration of test material in vehicle: not stated

Duration of treatment / exposure:

Single treatment

Frequency of treatment:

Single treatment

Post exposure period:

sampling at 24, 48 and 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
82.5 mg/kg
Basis:

No. of animals per sex per dose:

6 (control group) 7 (test group)

Control animals:

other: physiological saline

Positive control(s):

- cyclophosphamide
- Justification for choice of positive control(s): none given in report
- Route of administration: oral by gavage
- Doses / concentrations: 51.1 mg/kg bw

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: based po toxicity study

DETAILS OF SLIDE PREPARATION:
air dried, stained with panoptic stain method developed by Pappenheim

METHOD OF ANALYSIS: 1000 PCE s scored under microscope (magnification 650-1000 x) for incidence of PCEs with micronuclei. Ratio of PCE to NCE was calculated based on 1000 erythrocytes.

Evaluation criteria:

A substance producing clear statistically significant positive response at all three test points is considered mutagenic.

Statistics:

Poisson test was applied

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

positive

Toxicity:

yes

Remarks:

slight to moderate clonic convulsions (all animals)

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

No statistically significant increase in micronucleated PCEs observed in males and females at 48 hours.

No statistically significant increase in micronucleated PCEs observed in males at 24 hour or in females at 72 hours.

No statistically significant increase in micronucleated PCEs observed in females at 72 hours.

Statistically significant increase in micronucleated PCEs observed in males at 72 hours due to exceptionally low negative control value.

At 24 hours a clear statistically significant increase in micronucleated PCEs was observed in females (p=0.000)

At 24 hours a statistically significant increase in micronucleated PCEs was observed in females (p=0.076)

When these values are combined the positive result is clearly statistically significant (p=0.000)

The test was not repeated to confirm this result because of the nature of the test material, and other positive results (not described in report).

Table 1 Results of in vivo micronucleus test (5 animals/sex, 1000 cells evaluated per animal) 24 hour sampling time

Sampling time	Treatment	Male/female	PCE with MN	Ratio PCE/NCE*
24 hours	Negative Control	male	1.6 ± 1.14	1.71-2.45
		female	1.4 ± 0.55	1.67-1.97
	Test substance	male	3.2 ± 3.35	0.98-2.40
		female	7.2 ± 2.28	1.08-2.10
	Positive control	male	30.8 ± 13.66	1.70-2.24
		female	27.6 ± 4.45	0.90-1.82

 

Table 2 Results of in vivo micronucleus test (5 animals/sex, 1000 cells evaluated per animal) 48 hour sampling time

Sampling time	Treatment	Male/female	PCE with MN	Ratio PCE/NCE*
48 hours	Negative Control	male	0.6 ± 0.89	1.20-2.09
		female	1.6 ± 0.55	1.42-2.13
	Test substance	male	1.6 ± 1.52	0.96-1.82
		female	1.6 ± 0.89	1.06-2.01
	Positive control	male	18.8 ± 3.77	0.32-0.62
		female	5.8 ± 2.77	0.75-1.19

 

Table 3 Results of in vivo micronucleus test (5 animals/sex, 1000 cells evaluated per animal) 72 hour sampling time

Sampling time	Treatment	Male/female	PCE with MN	Ratio PCE/NCE*
72 hours	Negative Control	male	0.4 ± 0.55	2.55-4.05
		female	0.6 ±0.55	1.78-3.47
	Test substance	male	2.2 ± 1.48	1.22-2.97
		female	0.4 ± 0.89	1.78-2.91
	Positive control	male	7.0 ± 1.73	0.16-0.46
		female	3.8 ± 1.3	0.34-1.31

 

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
2,3-epoxypropyltrimethylammonium chloride has been tested in a valid study according to OECD 474 and under GLP. A statistically significant increase (p=0.000) in micronucleated PCEs was observed relative to the control at 24 hours (female, and both sexes combined). It is concluded that the test substance is positive for the induction of micronuclei under the conditions of the test.