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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited characterisation of test substance, reduced documentation of test animal welfare)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(limited documentation on test substance and test animals)
Principles of method if other than guideline:
BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
Test groups consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.

GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetramethyl-propylendiamin
- Analytical purity: no data
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Mean weight at study initiation: 189 g (males); 164 g (females)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 8 %

MAXIMUM DOSE VOLUME APPLIED: ca. 15 mL/kg bw

Doses:
400, 500, 640, 800, 1000, 1250 µL/kg bw (312, 390, 500, 624, 780, 975 mg/kg bw - based on the density d=0.78 g/cm³)
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 observation: daily
- Frequency of weighing: days 0, 3, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
0.8 mL/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
624 mg/kg bw
Based on:
test mat.
95% CL:
> 500 - < 780
Remarks on result:
other: based on the density d=0.78 g/cm³
Mortality:
975 mg/kg: 9/10 (2 males and 4 females died within 6 h post application. 3 further males died within 24 h post application.)
780 mg/kg: 7/10 (1 male and 2 females died within 24 h post application. 3 further males and 1 further female died within 7 days post application.)
624 mg/kg: 4/10 (1 female died within 24 h. 2 further females and 1 male died within 7 days.)
500 mg/kg: 1/10 (1 male died within 48 h.)
390 mg/kg: 1/10 (1 female died within 14 days.)
312 mg/kg: 1/10 (1 female died within 48 h.)
Clinical signs:
- 975 and 780 mg/kg: immediately after application: accelerated respiration; 1 h post application: abdominal position, mouth discharge, chewing reflex, in some animals dyspnoea; 3 h post application: red smeared snouts and ruffled fur; 2 days post application: crouched position, irregular gasping, agglutinated eyes and snouts, ruffled fur
- 624 and 500 mg/kg: in the first hours after application: accelerated respiration; 3 h post application: crouched position and ruffled fur; 3 days post application: crouched position, gasping, agglutinated eyes and snouts, ruffled fur
- 390 and 312 mg/kg: on day 1 post application: accelerated respiration and crouched position; 3 days post application: gasping and crouched position
Body weight:
Animals lost weight in the first 3 days post treatment but regained weight until the end of the observation period.
Gross pathology:
Animals that died during observation period: acute passive hyperemia; acute dilatation of the heart; glandular stomach reddened diffusely; isolated ulcerations; diarrhetic contents of the intestines; acinar pattern of the liver

Sacrificed animals: 975 mg/kg: 1x thickened forestomach-epithelium

Any other information on results incl. tables

Mortality:

 Dose: (mg/kg)

 Gender

 1 h

 24 h

 48 h

 day 7

 day 14

 975

 male

 0/5

 5/5

 5/5

 5/5

 5/5

 975

 female

 0/5

 4/5

 4/5

 4/5

 4/5

 780

 male

 0/5

 1/5

 3/5

 4/5

 4/5

780 

 female

 0/5

 2/5

 2/5

 3/5

 3/5

 624

 male

 0/5

 0/5

 0/5

 1/5

 1/5

 624

 female

 0/5

 1/5

 1/5

 3/5

 3/5

 500

 male

 0/5

0/5 

 1/5

 1/5

 1/5

 500

 female

 0/5

 0/5

 0/5

 0/5

 0/5

 390

 male

 0/5

 0/5

 0/5

 0/5

 0/5

 390

 female

 0/5

 0/5

 0/5

 0/5

 1/5

 312

 male

 0/5

 0/5

 0/5

 0/5

0/5 

 312

 female

 0/5

 0/5

 1/5

 1/5

 1/5

 

Weight (g):

Dose (mg/kg)

 Gender

 day 0

 day 3

 day 7

 day 13

 975

 male

 168

 -

 -

 -

 780

 male

 192

 171

 206

 246

 624

 male

 186

 164

 184

 211

 500

 male

 194

 175

 211

 231

 390

male 

 180

 174

207 

 210

 312

 male

 193

 200

 229

 236

 

 

 

 

 

 

 975

female 

 163

 143

 158

 159

 780

 female

 163

 149

 157

 172

 624

 female

 165

 154

 149

 231

 500

 female

 164

 147

 173

 173

 390

 female

 165

 146

 150

170 

 312

 female

 166

 178

 168

 181

Harmful if swallowed. There is indication that the test substance causes local irritation to exposed tissue.

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

The Acute oral toxicity of Tetramethylpropylendiamine (TMPDA) was evaluated in rats according an internal BASF method, which in principle is comparable to the OECD Guideline 401.

A test group consisting of 5 Sprague-Dawley rat/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.

At 975 mg/kg, 2 males and 4 females died within 6 h after treatment. 3 further males died within 24 after treatment.

At 780 mg/kg, 1 male and 2 females died within 24 h after treatment. 4 males and 3 females died within 7 days after treatment.

At 624 mg/kg, 1 female died within 24 h. 3 females and 1 male died within 7 days.

At 500 mg/kg, 1 male died within 48 h.

At 390 mg/kg, 1 female died within 14 days. 312 mg/kg: 1 female died within 48 h.

Under these experimental conditions, the oral LD50 of TMPDA is 624 mg/kg in rats.