Triphenyl phosphate

Endpoint summary

Description of key information

Acute toxicity after oral and dermal administration of triphenyl phosphate is very low. Acute oral administration in rats, mice, rabbits and guinea pigs produced LD50 values in a range of 3000 mg/kg body weight to above 20000 mg/kg body weight. After dermal application an LD50 >7900 mg/kg body weight was established in rabbits. No valid studies are available regarding inhalation exposure to TPP. A number of studies are available using other routes of exposure such as subcutaneous, intraperitoneal and intramuscular injections which confirm the low level acute toxicity of triphenyl phosphate.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Short report. Main features of study design given. Also assessed by OECD.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Similar to limit test but higher dose is used.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar derived
- Weight at study initiation: 200-300 grams
- Fasting period before study: 24hours
- Housing: mesh bottom cages
- Diet (e.g. ad libitum): Available after dosage
Water (e.g. ad libitum): Available after dosage

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% in aqueous solution

Doses:

Single dose of 20,000 mg/kg of the test material.

No. of animals per sex per dose:

5 males, 5 females (10).

Control animals:

no

Details on study design:

Ten young adult albino rats weighing between 200-300 grams equally distributed into five males and five females were housed in mesh-bottom cages and fasted 24 hours prior to administrating a single dose of 20,000 mg/kg of the test material. Food and water were available ad libitum after dosage. The animals were observed daily for 14 days following adminsitration of the test material and deaths were recorded.

Preliminary study:

No mortality was observed at the dosage level of 20,000 mg/kg of body weight. Gross examination at autopsy revealed sporadic visceral hemorrhage.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Mortality:

None

Clinical signs:

other: No information on clinical signs.

Gross pathology:

Gross examination at autopsy revleaed sporadic visceral hemorrhage.

Interpretation of results:

not classified

Conclusions:

The approximate acute oral LD50 for TPP in rats is >20,000 mg/kg of body weight.

Executive summary:

In an acute oral toxicity test in rats, ten young adult albino rats weighing between 200-300 grams equally distributed into five males and five females were housed in mesh-bottom cages and fasted 24 hours prior to administrating a single dose of 20,000 mg/kg of the test material TPP (in 25% aqueous solution). The dose was administered via intragastric intubation. Food and water were available ad libitum after dosage. The animals were observed daily for 14 days following administration of the test material and deaths were recorded. No mortality was observed at the administered dose. Gross examination at autopsy revealed sporadic visceral hemorrhage. The approximate acute oral LD50 obtained for the test material TPP is >20,000 mg/kg of body weight.

Endpoint conclusion

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

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: Short report, few details. Also assessed by OECD

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Method: other: as described in 16 CFR 1500.40

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: Albino

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

This study was conducted according to US Federal Hazardous Substances Act Regulations study guideline 16 CFR 1500.40. 5 rabbits were tested with intact skin and 5 with abraded skin. Observation period of 14 days.

Doses:

10000 mg/kg

No. of animals per sex per dose:

10

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Mortality:

None

Clinical signs:

other: No data

Gross pathology:

No data

MORTALITY: none

Interpretation of results:

not classified

Conclusions:

Dermal LD50 is > 10,000 mg/kg body weight.

Executive summary:

2 groups of 5 albino rabbits were treated each with a dose of 10 000 mg/kg body weight on either intact or abraded skin. No adverse effects nor mortality were observed during 14 -days post-exposure. The LD50 is >10,000 mg/kg body weight.

Endpoint conclusion

Dose descriptor:

LD50

Value:

7 900 mg/kg bw

Additional information

Non-guideline toxicity studies were performed mainly in rats and hens, but mice, rabbits, cats and guinea pigs were also used. Nevertheless, the acute toxicity could be evaluated from the available evidence.

There are also a number of studies using subcutaneous, intraperitoneal and intramuscular injections. The studies considered valid confirm the low level of toxicity. These routes of administration are not considered relevant for triphenyl phosphate exposure in man and are therefore not included in the overall chemical assessment. The data available on toxicity via oral dermal routes is sufficient (rated 2) and is listed in table.

Study Type	Species	Endpoint	Exposure	Result	Reference
Acute oral	Rat	LD50	single; dose level 20000 mg/kg bw	>20000 mg/kg bw	Mackellar DG, 1976
Acute oral	Rat	LD50	single; maximum dose level 15800 mg/kg bw	10800 mg/kg bw	Johannsen FR et al., 1977
Acute oral	Rat	LD50	single; dose levels 2500 - 5000 mg/kg bw	>5000 mg/kg bw	Ciba-Geigy, 1954
Acute oral	Mouse	LD50	single; dose levels 2500 - 5000 mg/kg bw	>5000 mg/kg bw	Ciba-Geigy, 1954
Acute oral	Guinea pig	LD0	single; dose levels 3000 -4000 mg/kg bw	>4000 mg/kg bw	Sutton WL et al., 1960
Acute oral	Hen	Neurotoxicity	single; undiluted, dose level 1000 mg/kg bw	No signs of neurotoxicity; >1000 mg/kg bw	Hine CH et al., 1956
Acute oral	Hen	Neurotoxicity	single; dose level 500 mg/kg bw in arachis oil	No signs of neurotoxicity; >500 mg/kg bw	Aldridge WN et al., 1961
Acute oral	Hen	Neurotoxicity	single; dose level 30g/kg in olive oil as gelatine capsules	No signs of neurotoxicity; >10000 mg/kg bw	Henschler D et al., 1958
Acute oral	Hen	LD0	single; dose level 5000 mg/kg bw in gelatine capsules	>5000 mg/kg bw	Johannsen FR et al., 1977
Acute oral	Hen	NOEL	single; dose level 2, 3, 5, 8, 12.5 g/kg in arachis oil	> 12500 mg/kg bw	Ciba-Geigy, 1980
Acute oral	Hen	NOEL	single; dose level 12000 mg/kg bw	> 12000 mg/kg bw	Ciba-Geigy, 1981
Dermal	Rabbit	LD50	single; dose level 10000 mg/kg bw	>10000 mg/kg bw	Mackellar DG, 1976
Dermal	Rabbit	LD50	sinlge; dose level 7900 mg/kg bw	>7900 mg/kg bw	Johannsen FR et al., 1977

Justification for classification or non-classification

The level of acute toxicity after oral and dermal administration is low and the LD50 values suggest that no classification is required for these routes of exposure.