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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from repeat dose study equivalent to guideline OECD408 used for assessment of toxicokinetic behaviour.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Subchronic toxicity study of tributoxyethyl phosphate in Wistar rats
Author:
Saitoh M, Umemura T, Kawasaki Y et al
Year:
1994
Bibliographic source:
Eiser Shikensko Hokoku 112: 27-39

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour from repeat dose toxicity study
Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 408
Principles of method if other than guideline:
Data from guideline repeat dose study used for toxicokinetic behaviour assessment.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
5 or 14 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
03, 0.3 or 3.0% in diet
No. of animals per sex per dose:
15

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
TBEP was absorbed from the digestive system into the hepatic portal circulation
Details on distribution in tissues:
Not measured
Details on excretion:
Not measured

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

The only significant toxicological findings were on the liver, indicating significant absorption of the test substance:

Serum cholinesterase activity was significantly decreased in both sexes in the 0.3 and 3.0% groups and serum gamma glutamyl transferase was significantly increased in both sexes in the top dose group after both 5 and 14-weeks of exposure. Serum amylase levels were also increased in males (0.3 and 3.0 % groups) and in females (3%).

Absolute and relative liver weights in both sexes were significantly increased in the top dose group (3.0%) after both 5 and 14-weeks of treatment.

Histopathological examination showed only male rats in the top dose group (3.0%) to exhibit moderate periportal hepatocyte swelling after 14-weeks.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
TBEP was absorbed from the diet into the hepatic portal circulation. The site of metabolism is likely to be the liver, which was the only target organ for toxicity in this study.
Executive summary:

In a study to evaluate the toxicity of TBEP to Wistar rats on repeated exposure,15 rats per sex per group aged 5-weeks were fed a diet containing 0.03, 0.3 or 3.0% TBEP for 5 weeks (7 rats per group) or 14 weeks (8 rats per group). The experimental details of this study are fully reported in section 7.5.1, repeat dose toxicity.

Serum cholinesterase activity was significantly decreased in both sexes in the 0.3 and 3.0% groups and serum gamma glutamyl transferase was significantly increased in both sexes in the top dose group after both 5 and 14-weeks of exposure. Serum amylase levels were also increased in males (0.3 and 3.0 % groups) and in females (3%).

Absolute and relative liver weights in both sexes were significantly increased in the top dose group (3.0%) after both 5 and 14-weeks of treatment.

Histopathological examination showed only male rats in the top dose group (3.0%) to exhibit moderate periportal hepatocyte swelling after 14-weeks.

It can be concluded that TBEP was absorbed from the digestive system. The only target organ was the liver, which is likely to be the site of metabolism of TBEP.