Triisopropyl phosphite

Acute Toxicity: oral

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

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triisopropyl phosphite

EC Number:

204-130-0

EC Name:

Triisopropyl phosphite

Cas Number:

116-17-6

Molecular formula:

C9H21O3P

IUPAC Name:

tris(propan-2-yl) phosphite

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 or test system 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:

other: 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 letharg

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	N°	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