Registration Dossier

Administrative data

Description of key information

Acute oral toxicity, GLP, OECD 401, male and female rats, substance solved in tap water, LD50 for both sexes 641 mg / kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 1994 - February 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Umweltministerium Baden-Württemberg, Stuttgart, Germany
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
Batch 3078183
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna Süddeutsche Versuchstierfarm, Oberer Bann 37, D-78532 Tuttlingen
- Veterinary preliminary examination: without morbid signs, females are nulliparous and non-pregnant
- Weight at study initiation: 181 - 241 g
- Fasting period before study: overnight
- Housing: individually in Macrolon cages (area 800 cm2, height 17 cm
- Diet (e.g. ad libitum): ALMA 0801 H 1003 (ALMA-Futter Friedrich Botzenhardt KG, D-87437 Kempten/Allgäu), twice 8 g daily
- Water (e.g. ad libitum): free access by daily changing of the watering bottles
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 : 12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Sample was diluted in the statet doses per kg body weight with 1.5 ml tap water and was administered to the rats by means of a stomach tube. Food was withheld for further 4 hours.
Doses:
Group I: 125 mg / kg bw
Group II: 500 mg / kg bw
Group III: 2000 mg / kg bw
No. of animals per sex per dose:
each group consists of 5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily weighing, observations on first day 5 min, 30 min, 4 h after administration, then daily
- Necropsy of survivors performed: yes
- Other examinations performed: behavior pattern and toxicological symptoms (changes of hair, skin, nose and mouth with muscous membrane, eye, anal region, excrements, urine (macroscopic), respiration, circulation, nervous system and behavoir
Statistics:
The LD50 calculation was performed according to "Moving Averages" (Shayne C. G.; Weil C. S.; in Hayes, Principles and Methods of Toxicology, Raven Press, New York 1984, Student Edition, 273).
Sex:
male
Dose descriptor:
other: mortality 20%
Effect level:
125
Based on:
test mat.
Remarks on result:
other: 1 out of 5 died
Sex:
female
Dose descriptor:
LD0
Effect level:
125
Based on:
test mat.
Remarks on result:
other: 0 out of 5 died
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
500
Based on:
test mat.
Remarks on result:
other: 1 out of 5 died
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
500
Based on:
test mat.
Remarks on result:
other: 2 out of 5 died
Sex:
male
Dose descriptor:
LD100
Effect level:
2 000
Based on:
test mat.
Remarks on result:
other: 5 out of 5 died
Sex:
female
Dose descriptor:
LD100
Effect level:
2 000
Based on:
test mat.
Remarks on result:
other: 5 out of 5 died
Mortality:
In group I one male animal was found dead in the morning of the eleventh day. In group II a male and a female animal died in the first hour after administration. One female animal was found dead in the morning of the second day. In group III two male and two female animal died during the first two hours after administration. All other animals were found dead in the morning of the first day.
Clinical signs:
Acute toxicological symptoms attributed to the exposure to the test substance could be observed in four rats of group I (125 mg / kg bw) and in all rats of group II (500 mg / kg bw) and of group III (2000 mg / kg bw).
Body weight:
see table below.
Gross pathology:
No macroscopical findings in group I and II. Macroscopical organ changes (dark-red coloured gut) in two male animals of group III.
Other findings:
no other findings reported

Body weight (statements in g):

female male
animal no. 620 621 622 623 624 625 626 627 628 629
group I, day 0 204 198 205 207 215 212 241 212 219 204
1 199 212 222 224 226 227 260 230 223 224
2 - - - - - - - - - -
3 217 218 238 227 241 231 271 243 233 220
4 224 216 229 230 237 232 272 243 229 214
5 223 218 224 235 234 230 268 244 224 214
6 226 228 226 232 238 228 275 243 216 225
7 221 227 233 234 242 230 276 247 195 220
8 223 231 235 230 246 235 283 251 177 222
9 - - - - - - - - - -
10 242 250 233 247 255 265 305 272 151 247
11 240 247 236 244 253 260 299 267 + 244
12 237 241 236 244 252 258 296 261 240
13 238 247 235 243 253 256 295 267 242
14 238 248 248 247 255 259 306 274 252
female male
animal no. 610 611 612 613 614 615 616 617 618 619
group II, day 0 206 194 193 190+ 208 197+ 207 198 211 200
1 212 185 200 210 219 215 222 219
2 215 + 202 223 221 214 236 224
3 212 202 219 224 225 235 218
4 - - - - - - -
5 215 205 221 230 223 239 222
6 211 209 220 227 225 238 221
7 212 207 222 226 220 232 219
8 216 209 225 229 225 236 225
9 216 204 223 233 223 240 230
10 223 209 225 234 230 241 228
11 - - - - - - -
12 235 227 244 265 261 274 262
13 227 227 241 267 257 271 263

14

236

231

243

261

251

267

259

female male
animal no. 560 561 562 563 564 565 566 567 568 569
group III, day 0 194 188+ 181+ 188 179 197 221+ 208 215+ 230
1 + + + + + +
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Harmful if swallowed Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material did induce mortality in the dose groups of 2000 mg/kg bw (100 % mortality), 500 mg/kg bw (30 % mortality) and 125 mg/kg bw (10 % mortality) and treatment-related clinical signs in all dose groups. According to OECD guideline 401 the LD50 of the test item is 641 mg/kg bw. The test material was considered to be harmful if swallowed after oral application under the conditions of the test and has to be classified as GHS Category 4.
Executive summary:

The test substance was administered orally in a single dose to three groups of Sprague-Dawley rats:

Group I (5 male and 5 female rats), 125 mg / kg bw applied

Group II (5 male and 5 female rats), 500 mg / kg bw applied

Group III (5 male and 5 female rats), 2000 mg / kg bw applied

Acute toxicological symptoms attributed to the exposure to Lekutherm Beschleuniger KU 6519 could be observed in four rats of group I and in all rats of group II and of group III. The post-mortem-findings of all 30 rats of the test show macroscopical organ changes of the gut of two rats out of 10 of the dosage group of 2000 mg / kg bw. The other rats show no macroscopical organ changes in the pathological examinatioon. The LD50 value of Lekutherm Beschleuniger KU 6519 was estimated to be 707 mk/kg bw for male rats and 574 mg / kg bw for female rats addording to the calculation by moving averages interpolation.

The LD50 value for both sexes is 641 mg / kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
641 mg/kg bw

Additional information

The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material did induce mortality in the dose groups of 2000 mg/kg bw (100 % mortality), 500 mg/kg bw (30 % mortality) and 250 mg/kg bw (10 % mortality) and treatment-related clinical signs in all dose groups. According to OECD guideline 401 the LD50 of the test item is 641 mg/kg bw. The test material was considered to be harmful if swallowed after oral application under the conditions of the test and has to be classified as GHS Category 4.


Justification for selection of acute toxicity – oral endpoint
well documented GLP-guideline Study, which used a vehicle without concern.

Justification for classification or non-classification

According to OECD guideline 401 the LD50 of the test item is 641 mg/kg bw. The test material was considered to be harmful if swallowed after oral application under the conditions of the test and has to be classified as GHS Category 4.