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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:
05.10.1985 - 05.09.1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Restrictions: sesame oil instead of water; large differences in dose volume (0. to 3.2 mL/kg depending on dose).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Cited as Directive 84/449/EEC, B.1
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
. Dose volume varied from 0.8 to 3.2 ml/kg bw, depending on dose level.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): N,N-dimethylbutylamin
- Substance type: aliphatic amine
- Physical state: liquid
- Analytical purity: 99%
- Lot/batch No.: RM 13 2972; date: 07.06.1985
- Test material received: 26.06.1985
- Radiochemical purity (if radiolabelling):
- Storage condition of test material: at 22°C in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: males 6 weeks; females 9 weeks
- Weight at study initiation: males 168.2 +/- 6.7 g; females 188.7 +/- 9.7 g;
- Fasting period before study: 16 hours
- Housing: in groups of 5
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: min 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): no data
- Photoperiod: (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5% at low dose; 25% at dose levels 200, 250, and 313 mg/kg bw
- Amount of vehicle (if gavage): 3.2 / 0.8 / 1.0 / 1.26 mL/kg bw at 160 / 200 /250 / 315 mg/kg bw
- Justification for choice of vehicle: not reported
- Purity: pharmaceutical grade

MAXIMUM DOSE VOLUME APPLIED: 3.2 mL/kg bw

DOSAGE PREPARATION: test substance was suspended in vehicle using a magnetical stirrer
Doses:
160, 200, 250, and 315 mg/kg bw (5 - 25 % in oil)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
-- observations: at 0.1, 0.5, 1, 2, 4, and 6 hours after dosing, then at least once a day during the 14-day observation period
-- weighing: day 0 (before dosing), days 7, 14, and 21 (females only) after dosing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Probitanalysis

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
258 mg/kg bw
Based on:
test mat.
95% CL:
208 - 330
Remarks on result:
other: Free base. A combined male/female LD50 could not be generated
Sex:
female
Dose descriptor:
LD50
Effect level:
184 mg/kg bw
Based on:
test mat.
95% CL:
139 - 224
Remarks on result:
other: Free base
Mortality:
All deaths occurred within 0.5 to 2 hours after dosing. The LD50 was 258 mg/kg bw (95% CI 208 - 330) for males and 184 mg/kg bw (95% CI 139 - 224) for females.
Clinical signs:
Hunched posture, piloerection, bloody lacrimation, hypoactivity, rattling and forced respiration, at the higher doses (250 and 315 mg/kg bw), and convulsions and trembling in all female groups.
Body weight:
Surviing animals gained approx. 50% weight compared to body weight at study initiation.
Gross pathology:
In deceased animals, dark to black discoloration of the liver, petechial hemorrhage in the gastro-intestinal tract with bloody mucous in the stomach. No changes were noted in surviving animals.

Any other information on results incl. tables

MORTALITY

Dose

mg/kg bw

male

female

160

 

2/5

200

0/5

2/5

250

3/5

5/5

315

4/5

5/5

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
N,N-dimethylbutylamine is acutly toxic. Under the conditions of the study the oral LD50 was 258 (males) and 184 (females) mg/kg (gavage, Wistar rats).
Executive summary:

The acute oral toxicity of N,N-dimethylbutylamine (160, 200, 250, 315 mg/kg bw; suspended in sesame oil) was examined in a guideline study (OECD 401) under GLP conditions. Young Wistar rats (5 per dose and sex) were treated and reactions were observed during the 14-day observation period.

Deaths occurred within 2 hours after dosing. The LD50 was 258 mg/kg bw in males and 184 mg/kg bw in females. A combined LD50 value could not be calculated. Signs of corrosion were seen in the gastro-intestinal tract of victims but not in animals that were sacrificed at the end of the observation period (Markert and Weigand, 1985)

 

Deviations from the test guideline include the use of a vehicle (sesame oil) instead of water. The dose volume varied largely across groups (0.8 to 3.2 mL/kg bw) and exceeded the recommended volume (1.0 mL/kg bw; OECD 401) in the low dose groups. The study is, however, considered to be valid and suitable for assessment, taking into consideration the lower LD50 value (184 mg/kg bw) for both male and female rats.