Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented and scientifically acceptable study.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Principles of method if other than guideline:
Tubular necrosis was determined according to Calder et al (1979) and Soderlund et al (1980).
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tris-CP
- Obtained from Chem.Service, West Chester, PA
- Analytical purity not stated

Test animals

Species:
rat
Strain:
Wistar
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mollegaard Breeding Centre, Ejby, Denmark
- Weight at study initiation: 180-250 g
- Diet (e.g. ad libitum): standard pellet diet (Ewos R 3, Astra Ewos, Sodertalje, Sweden) at libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
DMSO
Details on exposure:
Wistar rats, 10 per group, received a single intraperitoneal dose of 500 mg of the test substance per kg bodyweight in DMSO (<0.25 ml/100 g bodyweight). The control group received vehicle alone.
Doses:
0 and 500mg/kg bw.
No. of animals per sex per dose:
10 animals per dose group.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 48 hours
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: kidneys only
- Other observations: plasma urea, creatinine and glutamic oxalacetic transaminase were determined using convetional reagent kits.
Statistics:
All statistical comparisons were carried out using Student's t-test.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 500 mg/kg bw
Mortality:
one rat in the Tris-CP treatment group died.
Body weight:
- Kidney/body weight ratios were significantly increased over the controls
Gross pathology:
- TDCP did not cause any signs of nephrotoxicity (no histopathological changes)
- No histopathologcal changes indicative of cell necrosis were found in the kidneys.
- No histological evidence of liver necrosis
Other findings:
- No changes in plasma urea and creatinine were observed.

Applicant's summary and conclusion

Conclusions:
500mg Tris-CP injected intraperitoneally in Wistar rats does not cause significant histopathological changes in kidney, but does show increased kidney / body weight ratios.