Registration Dossier

Administrative data

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: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Triphenyl phosphite
- Commercial purity: > 97% (Phosphorus content = 10.0 %)
- Lot/batch No.: TPPx-Z18-04080A
- Supplier: Borg Warner Company, Parkersburg, WV

Test animals

Species:
rat
Strain:
other: Sherman-Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 and 300 grams
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR, Part 3.
- Fasting period before study: Animals were fasted overnight, but were not deprived of water.
- Diet: Following administration the animals were allowed food ad libitum
- Water: Following administration the animals were allowed water ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The sample was dosed as supplied (described as a colorless to straw-colored liquid).
Doses:
1.00, 1.26, 1.41, 1.58, 2.00, 2.51, 3.16, and 3.98 g/kg (males)
1.00, 1.26, 1.58, 1.78, 2.00, 2.51, 3.16, and 3.98 g/kg (females)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: rats were observed daily for signs of toxicity and mortality.
Statistics:
The LD50 was calculated using the method described by Finney, D.J. 1971. ‘Statistical Methods in Biological Assay', 2nd Edition, London Griffen Press.

Results and discussion

Preliminary study:
In the initial limit dose experiment with 5 g/kg, within 1 hour the animals were depressed and ruffled, after 2-3 hours the animals were comatose. All animals died within 18 hours. Gross pathological examination revealed no remarkable findings. Because the LD50 was < 5 g/kg, a definitive LD50 study was performed.
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1.59 other: g/kg
95% CL:
1.45 - 2.13
Mortality:
At the highest four doses in both males and females (2.00 to 3.98 g/kg) the animals died within 1-18 hours.
Clinical signs:
At the highest four doses in both males and females (2.00 to 3.98 g/kg), signs of toxicity (severe depression, ruffled appearance, drooling, ataxia) appeared within 1-2 hours, the animals became comatose within 2-3 hours. At the lower doses in males (1.26 to 1.58) and females (1.26 to 1.78), signs of toxicity were not as severe (slight or moderate depression, ruffled appearance, drooling) after 1-2 hours. Those that died became severely lethargic and comatose after 3-4 hours and were found dead within 18 hours. Those that survived at these doses appeared recovered and normal within 24-48 hours. At a dose of 1.00 g/kg in males and females, animals were slightly depressed and ruffled after a few hours and appeared normal by 24 hours.
Gross pathology:
Gross pathological examination revealed nothing remarkable.

Any other information on results incl. tables

The doses and number animals at each dose that died are presented below:

   Males    Females
 Dose  Study days  Dose  Study days
   1  2  3 - 21    1  2  3 -21
 1.00  0  0  0  1.00  0
 1.26  0  0  0  1.26 1  0
 1.41  1  0  0  1.41 1
 1.58  2  0 -  1.58  0  0
 2.00  5 - -  2.00 5
 2.51  5 -  2.51  -
 3.16  5 - -  3.16  -
 3.98  5 - -  3.98  -

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 (rat) of 1.59 g/kg bw, results in TPP being classified as a Category 4 Acute Toxicity based on teh GHS/CLP criteria.
Executive summary:

LD50 (rat) -1.59 g/kg bw - Category 4 Acute Toxicity.