1,3-bis[3-(dimethylamino)propyl]urea

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

bisDMAPAU and monoDMAPU were tested in the Ames bacterial reverse mutation assay. Both materials were found to be non-mutagenic under the conditions of this test.

monoDMAPAU was shown to be non-clastogenic to CHL cells in vitro. In Silico Studies (Derek KB 2020 1.0) predicted the registered substance to be negative for gene mutation in vitro in mammalian cells

Based on the presence of approximately 15% of 1,3-bis[3-(dimethylamino)propyl]urea.(bisDMAPAU) in the test item, and according to the attached read-across justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2022-06-22

Reliability:

2 (reliable with restrictions)

Qualifier:

no guideline available

Principles of method if other than guideline:

- Software tool(s) used including version: Derek Nexus: 6.1.0, Nexus: 2.3.0Sarah Nexus, 1.8
- Model(s) used: Derek Nexus, and Sarah Nexus
- Model description: see field 'Justification for non-standard information', 'Attached justification' and/or 'Cross-reference'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'Cross-reference'

GLP compliance:

no

Type of assay:

in vitro mammalian cell gene mutation tests using the thymidine kinase gene

Specific details on test material used for the study:

Smiles: CN(C)CCCNC(=O)NCCCN(C)C

Exact Mol Mass 230.2107
Average Mol Mass 230.35 (Source: Lhasa Limited, version 1.0)
Log Kp -3.43 (Source: Potts & Guy, version 1.0)
Log P 0.98 (Source: BioByte Corp., version 5.9)

Key result

Species / strain:

other: in silico

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: in silico

Vehicle controls validity:

not applicable

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

For the Mutagenicity in vitro endpoint with the Sarah Model - 2020.1 model, the compound is predicted to be Negative with 44% confidence in the prediction   

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

The standard test method for this study type ("General Study Plan" in OECD terminology) was reviewed for compliance once only on initial production.
Inspection of the routine and repetitive procedures that constitute the study is carried out as a continuous process designed to encompass the major phases at or about the time this study was in progress.

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Sponsor's identification: 3-DMAPAU
Description: Extremely pale straw coloured viscous liquid
Chemical name: 3-(Dimethylamino) propylurea
Purity: 83.8%
Batch number: 16602-102RW
Label : YBI-AB4-013-//MONO-DWAU 3-(dimethylamine) propylurea
Date received: 22 August 2002
Storage conditions: Room temperature in the dark under nitrogen

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Test concentrations with justification for top dose:

0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 μg/plate

Vehicle / solvent:

sterile distilled water

Untreated negative controls:

no

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

Nutrient Broth: Fluka, 4825911 52400
Period of pre-culture: 10 hr
Culture flask (form, size): Costar 75 cm' tissue culture flasks
Amount of culture medium: 5 ml
Amount of strain inoculated: 20 μl

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Conclusions:

The test material was considered to be non-mutagenic under the conditions of this test.

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

This study was conducted according to a method which was designed to assess the potential chromosomal mutagenicity of a test material on the metaphase chromosomes of the Chnese Hamster Lung (CHL) cell line according to the requirements of the Japanese New Chemical Substance Law (METI), OECD 473 and the updated Annex V B10 Method.

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

The Chnese Hamster Lung (CHL) cell line, isolated by Koyama et a1 (1970) and cloned by Ishidate and Sofuni (1985), was used. The CHL cell line has an average generation time of approximately 17 hours when growing under normal experimental conditions.

Species / strain / cell type:

other: Chnese Hamster Lung (CHL)

Details on mammalian cell type (if applicable):

The Chnese Hamster Lung (CHL) cell line, isolated by Koyama et a1 (1970) and cloned by Ishidate and Sofuni (1985), was used. The CHL cell line has an average generation time of approximately 17 hours when growing under normal experimental conditions.

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The maximum recommended dose level of 10 mM was used in all cases.

Vehicle / solvent:

DMSO was selected as the solvent because the test material was soluble at the maximum required concentration.

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

Details on test system and experimental conditions:

Duplicate cultures of Chinese Hamster Lung (CHL) cells were treated with the test material at several dose levels, together with vehicle and positive controls. Five exposure groups were used: Experiment 1 included a 6(18)-hour exposure, both with and without the addition of an induced rat liver homogenate metabolising system; Experiment 2 included a 24-hour continuous exposure, a 48-hour continuous exposure and a repeat of the 6(18)-hours exposure with metabolic
activation.
The dose levels evaluated in the main experiments were selected from a range of dose levels based on the results of a preliminary toxicity test and were in the range of 18 1.5 to 1452 pglml for all of the exposure groups.

Evaluation criteria:

In all circumstances where increases in the frequency of cells with aberrations are seen, statistical comparisons will be made with the vehicle. A positive response was recorded for a particular treatment if the % cells with aberrations, excluding gaps, markedly exceeded that seen in the concurrent control, either with or without a clear dose-relationship.
For modest increases in aberration frequency a dose response relationship is generally required and appropriate statistical tests may be applied in order to record a positive response.

Key result

Species / strain:

other: Chnese Hamster Lung (CHL)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks:

All the positive control chemicals induced highly significant increases in the frequency of cells with aberrations indicating the satisfactory performance of the test and of the activity of the metabolizing system.

Additional information on results:

The test material did not induce any toxicologically significant, dose-related increases in the frequency of cells with chromosome aberrations, either in the presence or absence of a liver enzyme metabolising system, or after various exposure times. The test material was therefore considered to be non-clastogenic to CHL cells in vitro.

Remarks on result:

other:

Remarks:

The test material did not induce any significant increases in the frequency of cells with aberrations in any of the exposure groups. The test material was shown to be non-toxic to CHL cells in vitro and the maximum recommended dose level of 10 rnM was used in all cases.

Conclusions:

3-DMAPAU was shown to be non-clastogenic to CHL cells in vitro.

Executive summary:

Duplicate cultures of Chnese Hamster Lung (CHL) cells were treated with the test material at several doselevels, together with vehicle and positive controls. Five exposure groups were used: Experiment 1 includeda 6(18)-hour exposure, both with and without the addition of an induced rat liver homogenate metabolizingsystem; Experiment 2 included a 24-hour continuous exposure, a 48-hour continuous exposure and a repeatof the 6(18)-exposure with metabolic activation.The dose levels evaluated in the main experiments were selected from a range of dose levels based on theresults of a preliminary toxicity test and were in the range of 181.5 to 1562 pglml for all of the exposuregroups.The vehcle (solvent) controls gave frequencies of cells with aberrations within the range expected for theCHL cell line. All the positive control chemicals induced highly significant increases in the frequency ofcells with aberrations indicating the satisfactory performance of the test and of the activity of themetabolizing system. The test material did not induce any significant increases in the frequency of cellswith aberrations in any of the exposure groups. The test material was shown to be non-toxic to CHL cells invitro and the maximum recommended dose level of 10rnMwas used in all cases.

Reference 4

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The test item was a mixture of the reaction products (1-(3-(Dimethylamino)propyl)urea (CAS 31506-43-1, EC 401-950-2, monoDMAPAU) )and 1,3-bis[3-(dimethylamino)propyl]urea (CAS 52338-87-1, EC 257-861-2, bisDMAPAU)

Both source (1-(3-(Dimethylamino)propyl)urea (CAS 31506-43-1, EC 401-950-2) )and target 1,3-bis[3-(dimethylamino)propyl]urea (CAS 52338-87-1, EC 257-861-2) substances are based on the reaction product of dimethylaminopropylamine (DMAPA) and urea.
The main product of this reaction is the singly-substituted urea product, (3-(dimethylamino)propyl) urea (or mono-DMAPAU)
However, an unavoidable side-reaction is the formation of the doubly-substituted product, 1,3-bis[3-(dimethylamino)propyl]urea, which is formed by the disproportionation of mono-DMAPAU.
The test item will contain approximately 13% of 1,3-bis[3-(dimethylamino)propyl]urea.
Read-across is also claimed based on structural similarity and properties of both reaction products. Justification attached.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

This study was conducted according to a method which was designed to assess the potential chromosomal mutagenicity of a test material on the metaphase chromosomes of the Chnese Hamster Lung (CHL) cell line according to the requirements of the Japanese New Chemical Substance Law (METI), OECD 473 and the updated Annex V B10 Method.

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

The Chnese Hamster Lung (CHL) cell line, isolated by Koyama et a1 (1970) and cloned by Ishidate and Sofuni (1985), was used. The CHL cell line has an average generation time of approximately 17 hours when growing under normal experimental conditions.

Species / strain / cell type:

other: Chnese Hamster Lung (CHL)

Details on mammalian cell type (if applicable):

The Chnese Hamster Lung (CHL) cell line, isolated by Koyama et a1 (1970) and cloned by Ishidate and Sofuni (1985), was used. The CHL cell line has an average generation time of approximately 17 hours when growing under normal experimental conditions.

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The maximum recommended dose level of 10 mM was used in all cases.

Vehicle / solvent:

DMSO was selected as the solvent because the test material was soluble at the maximum required concentration.

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

Details on test system and experimental conditions:

Duplicate cultures of Chinese Hamster Lung (CHL) cells were treated with the test material at several dose levels, together with vehicle and positive controls. Five exposure groups were used: Experiment 1 included a 6(18)-hour exposure, both with and without the addition of an induced rat liver homogenate metabolising system; Experiment 2 included a 24-hour continuous exposure, a 48-hour continuous exposure and a repeat of the 6(18)-hours exposure with metabolic
activation.
The dose levels evaluated in the main experiments were selected from a range of dose levels based on the results of a preliminary toxicity test and were in the range of 18 1.5 to 1452 pglml for all of the exposure groups.

Evaluation criteria:

In all circumstances where increases in the frequency of cells with aberrations are seen, statistical comparisons will be made with the vehicle. A positive response was recorded for a particular treatment if the % cells with aberrations, excluding gaps, markedly exceeded that seen in the concurrent control, either with or without a clear dose-relationship.
For modest increases in aberration frequency a dose response relationship is generally required and appropriate statistical tests may be applied in order to record a positive response.

Key result

Species / strain:

other: Chnese Hamster Lung (CHL)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks:

All the positive control chemicals induced highly significant increases in the frequency of cells with aberrations indicating the satisfactory performance of the test and of the activity of the metabolizing system.

Additional information on results:

The test material did not induce any toxicologically significant, dose-related increases in the frequency of cells with chromosome aberrations, either in the presence or absence of a liver enzyme metabolising system, or after various exposure times. The test material was therefore considered to be non-clastogenic to CHL cells in vitro.

Remarks on result:

other:

Remarks:

The test material did not induce any significant increases in the frequency of cells with aberrations in any of the exposure groups. The test material was shown to be non-toxic to CHL cells in vitro and the maximum recommended dose level of 10 rnM was used in all cases.

Conclusions:

monoDMAPAU was shown to be non-clastogenic to CHL cells in vitro.
Based on the presence of approximately 13% of 1,3-bis[3-(dimethylamino)propyl]urea.(bisDMAPAU) in the test item, and according to the attached read-across justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU).

Executive summary:

Duplicate cultures of Chnese Hamster Lung (CHL) cells were treated with the test material at several doselevels, together with vehicle and positive controls. Five exposure groups were used: Experiment 1 includeda 6(18)-hour exposure, both with and without the addition of an induced rat liver homogenate metabolizingsystem; Experiment 2 included a 24-hour continuous exposure, a 48-hour continuous exposure and a repeatof the 6(18)-exposure with metabolic activation.The dose levels evaluated in the main experiments were selected from a range of dose levels based on theresults of a preliminary toxicity test and were in the range of 181.5 to 1562 pglml for all of the exposuregroups.The vehcle (solvent) controls gave frequencies of cells with aberrations within the range expected for theCHL cell line. All the positive control chemicals induced highly significant increases in the frequency ofcells with aberrations indicating the satisfactory performance of the test and of the activity of themetabolizing system. The test material did not induce any significant increases in the frequency of cellswith aberrations in any of the exposure groups. The test material was shown to be non-toxic to CHL cells invitro and the maximum recommended dose level of 10rnMwas used in all cases.

Reference 5

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016 - 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Identification: Dabco NE1080
Physical state/Appearance: Clear colourless slightly viscous liquid
Batch: 2153125
Purity: Mono-constituent
Expiry Date: 16 April 2018
Storage Conditions: Room temperature in the dark

Test concentrations with justification for top dose:

The dose range for Experiment 1 was predetermined and was 1.5 to 5000 µg/plate.
The dose range was amended following the results of Experiment 1 and was 15 to 5000 µg/plate.

Vehicle / solvent:

sterile distilled water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA were treated with the test item using both the Ames plate incorporation and pre-incubation methods at up to eight dose levels, in triplicate, both with and without the addition of a rat liver homogenate metabolizing system (10% liver S9 in standard co-factors).
The dose range for Experiment 1 was predetermined and was 1.5 to 5000 µg/plate. The experiment was repeated on a separate day (pre-incubation method) using fresh cultures of the bacterial strains and fresh test item formulations. The dose range was amended following the results of Experiment 1 and was 15 to 5000 µg/plate. Six test item concentrations were selected in Experiment 2 in order to achieve both four non-toxic dose levels and the potential toxic limit of the test item following the change in test methodology.

Evaluation criteria:

The reverse mutation assay may be considered valid if the following criteria are met:
- All bacterial strains must have demonstrated the required characteristics as determined by their respective strain checks according to Ames et al., (1975), Maron and Ames (1983), Mortelmans and Zeiger (2000), Green and Muriel (1976) and Mortelmans and Riccio (2000).
- All tester strain cultures should exhibit a characteristic number of spontaneous revertants per plate in the vehicle and untreated controls (negative controls) within acceptable ranges.
- All tester strain cultures should be in the range of 0.9 to 9 x 109 bacteria per mL
- There should be a minimum of four non-toxic test item dose levels.
- There should be no evidence of excessive contamination.

Statistics:

Statistical significance was confirmed by using Dunnetts Regression Analysis (* = p < 0.05) for those values that indicate statistically significant increases in the frequency of revertant colonies compared to the concurrent solvent control.

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

Dabco NE1080 was considered to be non-mutagenic under the conditions of this test.

Executive summary:

Salmonella typhimuriumstrains TA1535, TA1537, TA98 and TA100 andEscherichia colistrain WP2uvrAwere treated with the test item using both the Ames plate incorporation andpre-incubation methods at up to eight dose levels, in triplicate, both with and without theaddition of a rat liver homogenate metabolizing system (10% liver S9 in standard co-factors).

The maximum dose level of the test item in the first experiment was selected as the maximumrecommended dose level of 5000 µg/plate. There was no visible reduction in the growth ofthe bacterial background lawn at any dose level, either in the presence or absence ofmetabolic activation (S9-mix), in the first mutation test (plate incorporation method) andconsequently the same maximum dose level was used in the second mutation test. However,after employing pre-incubation methodology in the second mutation test, a visible reductionin the growth of the bacterial background lawns of all of theSalmonellastrains was noted at5000 µg/plate in both the presence and absence of metabolic activation (S9-mix). No toxicitywas noted toEscherichia colistrain WP2uvrAin the second mutation test at any test itemdose level in either the presence or absence of S9-mix. No test item precipitate was observedon the plates at any of the doses tested in either the presence or absence of S9-mix

There were no toxicologically significant increases in the frequency of revertant colonies recorded for any of the bacterial strains, with any dose of the test item, either with or withoutmetabolic activation (S9-mix) in Experiment 1 (plate incorporation method) or Experiment 2 (pre-incubation method).

A small, statistically significant increase in TA1535 revertant colony frequency was observed in the presence of S9-mix at5000 µg/plate in the first mutation test. This increase was considered to be of no biologicalrelevance because there was no evidence of a dose-response relationship or reproducibility

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Based on the presence of approximately 15% of 1,3-bis[3-(dimethylamino)propyl]urea.(bisDMAPAU) in the test item, and according to the attached read-across justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Species:

mouse

Sex:

male/female

Control animals:

yes

Positive control(s):

The known clastogen and cytostatic agent cyclophosphamide served as a positive controll - cyclophosphamide.

Key result

Sex:

male/female

Genotoxicity:

negative

Remarks:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Toxicity:

no effects

Remarks:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Vehicle controls validity:

not specified

Negative controls validity:

valid

Remarks:

Negative and positive controls were sacrificed after 24 hours only.

Positive controls validity:

valid

Remarks:

Cyclophosphamide, the positive control, had a clear clastogenic effect, as can be seen fiom the biologically relevant increase in polychromatic erythrocytes with micronuclei. An inhibition of erythropoiesis was not found here.

Conclusions:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Reference 2

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

The test item was a mixture of the reaction products (1-(3-(Dimethylamino)propyl)urea (CAS 31506-43-1, EC 401-950-2, mono-DMAPAU) and 1,3-bis[3-(dimethylamino)propyl]urea (CAS 52338-87-1, EC 257-861-2, bis-DMAPAU)
Both source (1-(3-(Dimethylamino)propyl)urea (CAS 31506-43-1, EC 401-950-2) )and target 1,3-bis[3-(dimethylamino)propyl]urea (CAS 52338-87-1, EC 257-861-2) substances are based on the reaction product of dimethylaminopropylamine (DMAPA) and urea.
The main product of this reaction is the singly-substituted urea product, (3-(dimethylamino)propyl) urea (or mono-DMAPAU)
However, an unavoidable side-reaction is the formation of the doubly-substituted product, 1,3-bis[3-(dimethylamino)propyl]urea, which is formed by the disproportionation of mono-DMAPAU.
The test item will contain approximately 15% of 1,3-bis[3-(dimethylamino)propyl]urea.
Read-across is also claimed based on structural similarity and properties of both reaction products. Justification attached.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Species:

mouse

Sex:

male/female

Control animals:

yes

Positive control(s):

The known clastogen and cytostatic agent cyclophosphamide served as a positive controll - cyclophosphamide.

Key result

Sex:

male/female

Genotoxicity:

negative

Remarks:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Toxicity:

no effects

Remarks:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.

Vehicle controls validity:

not specified

Negative controls validity:

valid

Remarks:

Negative and positive controls were sacrificed after 24 hours only.

Positive controls validity:

valid

Remarks:

Cyclophosphamide, the positive control, had a clear clastogenic effect, as can be seen fiom the biologically relevant increase in polychromatic erythrocytes with micronuclei. An inhibition of erythropoiesis was not found here.

Conclusions:

No indications of a clastogenic effect of 3-(dimethylamino)propylurea were found after a sinde oral treatment of 5000 mg/kg.
Based on the presence of approximately 15% of 1,3-bis[3-(dimethylamino)propyl]urea.(bisDMAPAU) in the test item, and according to the attached read-across justification this result is also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)