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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: high purity of testmaterial (99,99%), sensitive species , low animal number used. Also assessed by OECD.

Data source

Reference
Reference Type:
publication
Title:
Does triphenyl phosphate produce delayed neurotoxic effects?
Author:
Wills JH, Barron K, Groblewski GE, Benitz KF, Johnson MK
Year:
1979
Bibliographic source:
Toxicology Letters 4(1), 21-24

Materials and methods

Principles of method if other than guideline:
neurotoxicity investigation in cats
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
zone-refined TPP (declared purity 99.99%)

Test animals

Species:
cat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
other: propylene glycol or corn oil
Doses:
400-700-1000 mg/kg
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
Five cats were given a single s.c dose of TPP dissolved in corn oil or propylene glycol and observed for signs of neurotoxicity for up to 3 months. One cat received 1000 mg/kg TPP in corn oil, and 2 received doses of 700 mg/kg TPP in corn oil and 2 received doses of 400 mg/kg TPP in propylene glycol. Control cats (2) received injections of corn oil or propylene glycol only. Parameters observed were mortality, necropsy.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
> 1 000 mg/kg bw
Body weight:
one cat in the 400 mg/kg dose group lost weight (about 31% of its original body weight). It returned to its normal body weight within 3 months. No signs of unusual weakness or ataxia during the 5 weeks after dosing.
2 cats receiving 700 mg/kg TPP became anorexic shortly after dosing and prostrate in 3-7 days after injection.
Cat in 1000 mg/kg group became anorexic after 1 week of dosing and by 3 weeks was prostrate having lost 48% of its body weight.
Gross pathology:
1/2 cats given 700 mg/kg TPP had Perforated ulcer in the stomach. 2/2 hyperemic intestines. Microscopic examination showed no evidence of neuropathology but did show generalised vascular damage with edema in many tissues, epecially the colon. Blood samples showed that cholinesterase levels were similar to the controls.
Sections of the brain and spinal cord did not reveal evidence of axon degeneration or demyelination of axons in any tract of the cat receiving 1000 mg/kg.

Any other information on results incl. tables

All cats dosed except one receiving 400 mg/kg lost weight.

The cat that lost weight after receiving 400 mg/kg (about 31% of its original body weight) showed no signs of unusual weakness or ataxia during the 5 weeks after dosing. It returned to about its original weight within 3 months and seemed to be normal in behavior and appearance.

The other cat receiving 400 mg/kg never showed any signs of toxicity.

The 2 cats given 700 mg/kg TPP became anorexic shortly after dosing and prostrate in 3-7 days after injection. One was found to have a perforated ulcer in the stomach, and both had hyperemic intestines. Microscopic examination showed no evidence of neuropathology, but did show generalized vascular damage with edema in many tissues,
especially the colon. Blood samples showed that
cholinesterase levels were similar to the controls.

The cat receiving 1000 mg/kg became anorexic 1 week after
injection and by 3 weeks was prostrate having lost 48% of
its body weight. Sections of the brain and spinal cord did
not reveal evidence of axon degeneration or demyelination of axons in any tract.

Applicant's summary and conclusion

Conclusions:
TPP is not neurotoxic to the cat when given s.c injections of 400, 700 or 1000 mg/kg TPP.
Executive summary:

Eight cats administered s.c. injections of 99.99% pure in corn oil or propylene glycol at dose levels of 400, 700 or 1000 mg/kg TPP did not exert neurotoxic effects in the cat. Body weight loss was noted in all but one animal in the low dose group. Histological examination of the brain and spinal cord did not show any adverse neurotoxic effects.