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Description of key information

The oral LD50 of 3-(dimethylamino)propylurea in rats was approximately 5125 mg/kg (5.0 ml/kg) of body weight.

The dermal LD50 of 3-(dimethylamino)propylurea in rats is greater than 2050 mg/kg of body weight.

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 these results are also deemed valid for 1,3-bis[3-(dimethylamino)propyl]urea (bisDMAPU).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1985
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, 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:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 96).
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Name: N-(3-(dimethylamino)-propy1)urea = HST 2844
Batch no.: Batch 12
Aggregate state: Liquid
External properties: Brownish clear liquid
Storage: At room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
We conducted the acute toxicity experiment with young adult SPF-bred Wistar rats (Bor strain: WISW (SPF Cpb), breeder: Winkelmann, Borchen) .
This rat is the species of choice for studying acute oral toxicity in mammal s.
The male and female rats were approximately 9 and 14 weeks old respectively at the start of the experiment.
The male animals had an average baseline weight of 162 g, the female animals 173 g.
The distribution of the animal weights was less than 20% from the mean.
The females were nullipara and not pregnant.
The health status of the animals was checked prior to the start of the experiment. Only symptom-free, healthy animals were used for the experiment.
Five rats were used per dose and sex.
Vehicle:
other: Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485)
Details on oral exposure:
The substance was formulated in Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485) at room temperature and administered once intragastrically to 5 maleand 5 female animals by using a rigid metal stomach probe at a constant application volume of 10 ml/kg of body weight.

The test substance was formulated immediately prior to the start of the experiment in the polyethylene glycol 400 (Lutrol) application medium, whereby each concentration was prepared separately. Because of the brief period of time between preparation and application, no analytical studies were performed with regard to stability in the application medium. A homogeneous mixture was obtained through mixing in a magnetic stirrer.

On the day of the application, the animals were inspected multiple times, twice daily during the 14-day observation period (once on weekends and holidays); as this was done, the type, start, duration and intensity of the clinical symptoms were logged, and dead animals were removed as necessary. The time of death of dead animals was logged.
Immediately before the application, one week after and at the end of the 14-day observation period, the surviving animals were weighed individually. The calculation of each animal's application volume was performed using the body weight recorded immediately before the application.
Doses:
10 ml/kg of body weight
No. of animals per sex per dose:
5 male and 5 female animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 5 126 mg/kg bw
Based on:
test mat.
Mortality:
The LD50 was approximately 5125 mg/kg of body weight.
Body weight:
Growth was influenced in one male rat from the 5125 mg/kg dosage
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of 3-(dimethylamino)propylurea (monoDMAPAu) in rats was approximately 5125 mg/kg (5.0 ml/kg) of body weight.
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:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 96).
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Name: N-(3-(dimethylamino)-propy1)urea = HST 2844
Batch no.: Batch 12
Aggregate state: Liquid
External properties: Brownish clear liquid
Storage: At room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
We conducted the acute toxicity experiment with young adult SPF-bred Wistar rats (Bor strain: WISW (SPF Cpb), breeder: Winkelmann, Borchen) .
This rat is the species of choice for studying acute oral toxicity in mammal s.
The male and female rats were approximately 9 and 14 weeks old respectively at the start of the experiment.
The male animals had an average baseline weight of 162 g, the female animals 173 g.
The distribution of the animal weights was less than 20% from the mean.
The females were nullipara and not pregnant.
The health status of the animals was checked prior to the start of the experiment. Only symptom-free, healthy animals were used for the experiment.
Five rats were used per dose and sex.
Vehicle:
other: Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485)
Details on oral exposure:
The substance was formulated in Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485) at room temperature and administered once intragastrically to 5 maleand 5 female animals by using a rigid metal stomach probe at a constant application volume of 10 ml/kg of body weight.

The test substance was formulated immediately prior to the start of the experiment in the polyethylene glycol 400 (Lutrol) application medium, whereby each concentration was prepared separately. Because of the brief period of time between preparation and application, no analytical studies were performed with regard to stability in the application medium. A homogeneous mixture was obtained through mixing in a magnetic stirrer.

On the day of the application, the animals were inspected multiple times, twice daily during the 14-day observation period (once on weekends and holidays); as this was done, the type, start, duration and intensity of the clinical symptoms were logged, and dead animals were removed as necessary. The time of death of dead animals was logged.
Immediately before the application, one week after and at the end of the 14-day observation period, the surviving animals were weighed individually. The calculation of each animal's application volume was performed using the body weight recorded immediately before the application.
Doses:
10 ml/kg of body weight
No. of animals per sex per dose:
5 male and 5 female animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 5 126 mg/kg bw
Based on:
test mat.
Mortality:
The LD50 was approximately 5125 mg/kg of body weight.
Body weight:
Growth was influenced in one male rat from the 5125 mg/kg dosage
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of 3-(dimethylamino)propylurea in rats was approximately 5125 mg/kg (5.0 ml/kg) of body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 125 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1985
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:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 103).
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Name: N-(3-(dimethylamino)-propy1)urea = HST 2844
Batch no.: Batch 12
Aggregate state: Liquid
External properties: Brownish clear liquid
Storage: At room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
other: Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485)
No. of animals per sex per dose:
5 male and 5 female animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 050 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
TThe dermal LD50 of 3-(dimethylamino)propylurea in rats is greater than 2050 mg/kg of bodv weight.
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:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
The studies were performed in accordance with EC Directives 84/449 (Official Journal of the European Communities 27, 1984, L 251, 103).
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Name: N-(3-(dimethylamino)-propy1)urea = HST 2844
Batch no.: Batch 12
Aggregate state: Liquid
External properties: Brownish clear liquid
Storage: At room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
other: Lutrol (manufacturer: Merck-Schuchard, Art. No.: 807485)
No. of animals per sex per dose:
5 male and 5 female animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 050 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
TThe dermal LD50 of 3-(dimethylamino)propylurea in rats is greater than 2050 mg/kg of bodv weight
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 050 mg/kg bw

Additional information

Justification for classification or non-classification