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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Remarks:
statement
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
N-(2-[2-(dimethylamine)ethoxy]ethyl)-N-methyl-1,3-propanediamine
Batch 19902-1
Purity >92%
Expiry date 31 October 2006

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered
to be approximately 15 air changes per hour, a temperature of 21.0 + 3.0•‹C (actual range: 19.7 -
21.7"C), a relative humidity of 30-70% (actual range: 43 - 69%) and 12 hours art'rficial
fluorescent light and 12 hours darkness per day.
Accommodation
Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18
cm.) containing sterilised sawdust as bedding material (Woody-Clean type 314; Tecnilab-BMI
BV, Someren, The Netherlands) and paper as cage-enrichment (Envirodri, BMI, Helmond, The
Netherlands).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet
Free access to standard pelleted laboratory animal diet (from Altromin (code VRF l), Lage,
Germany).
Water
Free access to tap water.
Certificates of analysis for ingredients and/or contaminants of diet, sawdust, paper and water
were examined and then retained in the NOTOX archives.
Results of analysis for ingredients and/or contaminants of diet, sawdust, paper, and water were
assessed and did not reveal any findings that were considered to have affected study integrity.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The vehicle (water) was selected based on trial formulations performed at NOTOX.
The formulations (wlw) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for the density of the test substance. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.
Doses:
300 mg/kg body weight, 2000 mg/kg body weight
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 300 mglkg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelinesThe onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD9 value).

Results and discussion

Preliminary study:
No preliminary study was performed.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Mortality:
Two females dosed at 2000 mg/kg were found dead on days 2 or 4. No further mortality occurred.
Clinical signs:
2000 mglkg - Lethargy, hunched posture, uncoordinated movements, ptosis, piloerection, chromodacryorrhoea
300 mglkg - Hunched posture and uncoordinated movements
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Other findings:
Macroscopic Finding
Macroscopic examination revealed abnormalities in the stomach (dark red discoloration, thickening of the glandular mucosa, irregular surface of the glandular mucosa) among the animals that died (2000 mg/kg). No abnormalities were found at macroscopic post mortem examination of the
surviving animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information LD50 > 300 and < 2000mg/kg b.w. Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of N-{2-[2-(Dimethylamine)Ethoxy]Ethyl)-N-Methyl-1,3-Propanediamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. The LD50 cutoff point is 1000 mg/kg b.w.
Executive summary:

The oral LD50 value of N-{2-[2-(Dimethylamine)Ethoxy]Ethyl)-N-Methyl-1,3-Propanediamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Initially, N- (2-[2-(Dimethylamine)Ethoxy]Ethyl ) -N-Methyl- l,3-Propanediamine was administered by oral

gavage to three female Wistar rats at 300 mgkg body weight. In a stepwise procedure additional groups of

females were dosed at 300 and 2000 m a g body weight. All animals were subjected to daily observations

and weekly determination of body weight. Macroscopic examination was performed on the day of death or

after terminal sacrifice (day 15 j.

Two females dosed at 2000 mgkg were found dead on days 2 or 4. No further mortality occurred.

The surviving animals had recovered from the symptoms between days 3 and 7.

Clinical signs : Lethargy, hunched posture, uncoordinated movements, ptosis, piloerection,

chromodacrvorrhoea

The body weight gain shown by the surviving animals over the study period was considered to be normal.

Macroscopic examination revealed abnormalities in the stomach (dark red discoloration, thickening of the

glandular mucosa, irregular surface of the glandular mucosa) among the animals that died (2000 mgkgj. No

abnormalities were found at macroscopic post mortem examination of the surviving animals.

The oral LD50 value of N32-[2-(D1METHYLAMINE)ETHOXflETHYL)-N-METHYL- ,3-PROPANEDIAMINE in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. The LD 50 cuoff point is 1000 mg/kg b.w.