Tributyl phosphate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EG-Richtlinie 84/449/EWG B.2.

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: TSCA-Guideline §798.1150

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tributyl phosphate

EC Number:

204-800-2

EC Name:

Tributyl phosphate

Cas Number:

126-73-8

Molecular formula:

C12H27O4P

IUPAC Name:

tributyl phosphate

Details on test material:

Purity: 99,62 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 2-3 months
- Weight at study initiation: 166 to 210 g
- Fasting period before study: none
- Housing: 5 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2
- Humidity (%): 40-50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 1989

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0, 511, 801, 2140, and 4242 mg/m³ air

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

LC50

Effect level:

> 4.242 mg/L air

Exp. duration:

4 h

Mortality:

2 male rats in dose group 4242 mg/L air died.

Clinical signs:

other: Group 3 ( 801 mg/L air) showed piloerection, diminuated motility, difficulties in breathing, bloody snout. Group 4 (2140 mg/L air) showed piloerection, untended fur, diminuated motility, nose secretion, sniffing sounds, bradypnoe, complications in breath

Body weight:

3 days after experiment in the male rats of group 2 (511 mg/L air) a retardation in weight gain and in groups 3 to 5 (801; 2140; 4242 mg/m³ air) a loss of weight could be observed.

Gross pathology:

died intercurrently: inflated, liver-like lung; red-crusted nose; anemic spleen and kidneys; changed liver signing; gastrointestinal trakt filled with yellow mucus.
Animals killed after observation period: inflated lung; effects in spleen (anemic, reduced in volume, enlarged, dark coloured); changed liver signing; inflated intestine.

Any other information on results incl. tables

Acute toxicity: inhalation: aerosol

N	Concentration nomin. analyt.    mg/m³ air		Toxicological result			Duration of symptoms	Timepoint od death	Particle < 5 µm (%)
Male rat
1	air-control		0*	0**	5***	-	-	-
2	2425	511	0	0	5	-	-	100
3	9700	801	0	5	5	4h-6h	-	100
4	13400	2140	0	5	5	4h-7h	-	100
5	48500	4242	2	5	5	4h-28d	2d	100
Female rat
1	air-control		0	0	5	-	-	-
2	2425	511	0	0	5	-	-	100
3	9700	801	0	5	5	4h-6h	-	100
4	19400	2140	0	5	5	4h-4d	-	100
5	48500	4242	0	5	5	4h-7d	-	100

LC50 male: approx. 4242 mg/m ³ air.

N= Group number

4h= direktly after exposition

*= Number of mortalities

**= Number of animals with symptoms

***= Number of animals used

Applicant's summary and conclusion

Executive summary:

Acute inhalative toxicity was tested with the test substance in male and female Wistar rats.

The doses tested for 4 hours were: 0; 511; 801; 2140; 4242 mg/m³ air.

Observed symptoms: diminuated motility, ataxie, adynamia in hindpaw, prostration, piloerection, untended fur, nose secretion, sniffing sounds, difficulties in breathing, bradypnoe, breathing sounds, chromodacryorrhoe, red-coloured urine, inflated abdomen, bloddy snout, loss of myotactic reflex, reduction of body weight. These symptoms point to a strong adverse effect to the respiratory tract.

After 4242 mg/m³ air 2 of 5 male rats died; the female rats in this dose group showed no mortalities.

The LD 50 was approx. 4242 mg/m³ air in the the more sensitive male rat.