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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:
No information on clinical signs.
Body weight:
No information on body weights.
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:
No data
Body weight:
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.