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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:
1994-03-05 to 1994-07-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with international standard guidelines under GLP conditions. The study report was conclusive and well enough documented with all relevant information included.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: clear liquid
Details on test material:
Lot #0-314-3033DR
Clear Liquid with density 0.93

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace animal
- Age at study initiation: 6 to 11 week
- Weight at study initiation: 201 to 293 g
- Fasting period before study: yes 16 to 20h prior dosing
- Housing: 5 per sex per cage (suspended wire mesh) Bedding was placed beneath the cagesand changed et least three time per week
- Diet (e.g. ad libitum): Fresh Purina Rodent Chow (Diet #5012)
- Water (e.g. ad libitum): Yes
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controlled but no data on the range
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hour light darh cycle

IN-LIFE DATES: From:1994-05-11 to To: 1994-006-09

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- No vehicle were used. Used as received and the dose was based on the sample weight as calculated from the specific gravity
Doses:
1000 and 2000 mg/kg
No. of animals per sex per dose:
5 per sex and dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observation at 1h, 2h, 4h post dose and once weekly for toxicity and phramacological effects. Animals were observed twice weekly for mortality.
Weighing: Once pretest, weekly and at termination
- Necropsy of survivors performed: yes
Statistics:
The LD 50 and 95% confidence limits were calculated if possible by the method Litchfield J.T Jr & F Wilcoxon JPET 96:99 1948 or Horn H. J. Biometrics 12:311 1956

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Mortality:
No mortality at 1000 mg/kg
2 males death at 2000 mg/kg
Clinical signs:
At 1000 mg/kg: Instances of theragy and ataxia ptosis and wetness of the anogenital area were noted on the day of dosing. All animals appeared normal from day 1 though day 14.

At 2000 mg/kg: Two males died by day 4 with predeath physical signs of lethargy, flaccid muscle tone, protration, negative righting reflex, coma, ataxia, and wetness of the anogenital area. Necropsy of the dead animals revealed abnormalities of the lungs, liver, testes, kidneys and gastrointestinal tract, as well as wetness of the anogenital area and red staining of the nose/mouth area. Physical signs noted in survivors included lethargy, flaccid muscle ton, ataxia and wetness of the anogenital area. All survivors appeared normal from day 2 through day 14.
Body weight:
No body weight change at the 2 doses tested on survival animals
Gross pathology:
Necropsy results were normal on the survivals animals.
Abnormalities of the lungs, liver, testes, kidneys and gastrointestinal tract for the 2 death animals
Other findings:
Wetness of the anogenital area and red staining of the nose and mouth area for the death anmals

Any other information on results incl. tables

Mortality table

Dose (mg/kg

Treated

Dead

 

Male

Female

Male

Female

1000

5

5

0

0

2000

5

5

2

0

 

Body weight and dose volume

Dose

Sex

Dosing volume (mL)

Body weight (g)

D0

D7

D14

1000

Male

1

0.28

262

317

350

2

0.31

283

355

402

3

0.29

272

347

386

4

0.30

281

348

394

5

0.32

293

373

410

Mean

278

348

388

S.D.

11.7

20.2

23.3

N

5

5

5

Female

6

0.24

220

267

282

7

0.24

222

256

266

8

0.26

239

281

308

9

0.22

207

244

265

10

0.23

211

251

259

Mean

220

260

276

S.D.

12.4

14.5

19.8

N

5

5

5

2000

Male

11

0.45

211 (dead hour 4 (207g))

12

0.46

214

298

342

13

0.43

201

258

283

14

0.48

223

313

364

15

0.49

227 (Dead day 4 (193 g))

Mean

215

290

330

S.D.

10.3

28.4

41.9

N

5

3

3

Female

16

0.48

224

262

285

17

0.46

215

251

272

18

0.46

212

248

277

19

0.44

206

234

260

20

0.44

205

241

262

Mean

212

247

271

S.D.

7.7

10.6

10.4

N

5

5

5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD 50 is greater than 2000 mg/kg
Executive summary:

The acute oral toxicity of Triisopropyl phosphite (TIPP) was assessed in a study on the rats according to the OECD Guideline 401 and in accordance with GLP.

The rats were given a single oral dose of test material at 1000 and 2000 mg/kg (5 animals per sex). The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

No mortality was observed at 1000 mg/kg. Clinical signs were observed up to 4 hours after treatment. No further signs were observed until sacrifice at day 14. Nothing was noted during the gross pathological examination.

At 2000 mg/kg, 2 males died: One 4 hours after dosing and one on day 4. For the survival animals, only some clinical signs were observed just after dosing. Nothing was noted during the gross pathology examination.

Under these experimental conditions, the LD50 was determinated to be greater than 2000 mg/kg for the Triisopropyl phosphite (TIPP).

Therefore, no classification is required according to the regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC criteria

This acute oral study is classified as acceptable. It satisfies the guideline requirement for an acute oral study in the rats