Tributyl phosphate

Endpoint summary

Description of key information

Several acute toxicity studies were performed with tributyl phosphate. Here only the reliable studies are reported: 
In the key study for acute oral toxicity an LD50 of 1553 mg/kg bw was found in rats. This value was supported by another study in rats were an LD50 of 1400 mg/kg bw was determined.
In the key study for acute dermal toxicity an LD50 > 3100 mg/kg bw (highest applied dose) was observed in rats.
Acute inhalation toxicity was determined with tributyl phosphate in male and female Wistar rats (key-study). The doses tested for 4 hours were 0, 511, 801, 2140 mg/m³, and the highest technically achievable concentration of 4242 mg/m³ air. At 4242 mg/m³ air 2 of 5 male rats died, whereas the female rats in this dose group showed no mortalities. Acute inhalation exposure to tributyl phosphate exerted clinical signs that were indicative of distinct irritation to the respiratory tract. The LD 50 was approx. 4242 mg/m³ air in the more sensitive male rat.

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No OECD guideline or GLP defined.

Qualifier:

according to guideline

Guideline:

other: EG-Richtlinie 84/449 (Amtsblatt der Europäischen Gemeinschaften 27, 1984, L 251, 96)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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: 9 (males) to 14 (females) weeks
- Weight at study initiation: 165 g for males and 163 g for females
- Fasting period before study: 16 h
- Housing: 5 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

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

IN-LIFE DATES: From: 1986-14-01 To: 1986-02-24

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1.3; 1.5; 1.8; 2,.0; 3.1 mL/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

body weight was determined before application, one week later and at the end of the 14-day observation period

Statistics:

after Rosiello et al., J. Tox. Environ. Health 3, 797, 1977

Dose descriptor:

LD50

Effect level:

1 552 mg/kg bw

Mortality:

1,5 ml/kg bw: 2 male/ 2 female
1,8 ml/kg bw: 3 male/ 4 female
2,0 ml/kg bw: 4 male/ 4 female
3,1 ml/kg bw: 5 male/ 5 female

Clinical signs:

other: Clinical signs were observed in dose groups: 1,5; 1,8; 2,0; 3,1 ml/kg bw.

Gross pathology:

No findings in dose group 1,3 ml/kg.
In dose group 1,5 ml/kg 4 rats (2 male/2 female) showed effects on gastric mucosa.
In the 1,8 ml/kg dose group 3 male animals showed effects on gastric mucosa and 4 female animals had effects on gastric mucosa, inflated intestine and reddened stomach.
In the 2,0 ml/kg dose group 4 male and 4 female animals showed effects on gastric mucosa, inflated intestines and a reddened lung. In the dose group of 3,1 ml/kg all animals (5male/ 5 female) showed effects on gastric mucosa, inflated intestines and a reddened lung.

After a single oral dose of 1,5 up to 3,1 ml/kg bw following symptoms could be observed in the test animals:

Diminished general condition; narcosis, bloody eye margins, face down position or lateral position, ruffled fur.

Executive summary:

Tributyl phosphate was tested in a single dose experiment in male and female Wistar rats.

The doses tested were: 1,3; 1,5; 1,8; 2,0; 3,1 ml/kg bw.

Signs of intoxication were: diminuated general condition; narcose, bloody eye margins, face down position or lateral position, ruffled fur.

The LD50 was: 1,6 ml/kg bw for male and female rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 553 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

other: TSCA-Guideline §798.1150

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 242 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: few experimental details - but sufficient for assessment

Principles of method if other than guideline:

undiluted test material was applied to intact, clipped skin (dorsal) of New Zealand albino male and female rabbits to determine the minimum lethal dose by the dermal route. Following application, treated areas were covered with plastic to preclude evaporation of the ester. Test material was washed off after the 24-hr exposure perid. animals were held for a 14-day observation period, after which they were sacrificed and subjected to gross autopsy.

GLP compliance:

not specified

Test type:

other: no data

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

no data

No. of animals per sex per dose:

no data

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 100 mg/kg bw

Remarks on result:

other: exposure: 24 hours

bo data

Executive summary:

Undiluted test material was applied to intact, clipped skin (dorsal) of New Zealand albino male and female rabbits to determine the minimum lethal dose by the dermal route. Following application, treated areas were covered with plastic to preclude evaporation of the ester. Test material was washed off after the 24-hr exposure perid. animals were held for a 14-day observation period, after which they were sacrificed and subjected to gross autopsy.

LD50 > 3100 mg/kg bw (rabbit)

reference: Johannsen (1977)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 100 mg/kg bw

Additional information

Tributyl phoshate was harmful by inhalation and if swallowed. In the key study for acute oral toxicity a LD50 = 1553 mg/kg bw was found. In the key study for acute inhalation toxicity a LC50 = 4242 mg/m³ (mortality 2/5) for male rats and LC50 > 4242 mg/m³ (mortality 0/0) for female rats was determined. By dermal application tributyl phosphate was only slightly toxic.

Justification for classification or non-classification

An LD50 of 1530 (oral, rat, male) was found in a valid study, therefore a classification with Acute Tox 4 (H302) is justified.
For inhalation an LC50 of 4242 mg/m³ (inhalation, rat, male) and LC50 > 4242 mg/m³ (inhalation, rat, female) was determined. 2/10 male rats died at this concentration (highest applied dose). A classification for acute inhalation toxicity is not warranted.
A classification for acute dermal toxicity is not justified based on an LD50 of > 2000 mg/kg bw.