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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Objective of study:
absorption
distribution
excretion
Test guideline
Qualifier:
according to
Guideline:
other: EPA Metabolism and Pharmacokinetic Test Guidelines (40 CFR 798)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Test compound: tri-n-butyl phosphate (TBP)
- Appearance: colorless, odorless liquid

non labeled TBP:
- Source: FMC corporation
- Received: 1990-12-06
- Purity: 99.7% pure
- Storage: room temperature

radiolabeled TBP:
- Source: American Radiolabeled Chemicals Inc. (ARC)
- Lot No.: 920505
- Received: 1992-05-27
- Purity: 98.7%
- Storage: ~20°C
- Specific activity: 55 mCi/mmol (ARC); 206.5 μCi/mg (MRI)
Radiolabelling:
yes

Test animals

Species:
guinea pig
Strain:
other: Yucatan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratory (Windham, Maine)
- Diet: ad libitum (Lab Mini-Pig Chow Starter)
- Water: ad libitum (Kansas City municipal water)
- Acclimation period: during the quarantine period, the pigs were acclimated to the dosing slings and individual steel cages 2 to 3 days for 1 to 5 h each day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-24
- Humidity (%): 30-60

Administration / exposure

Route of administration:
other: intravenous or dermal absorption

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
- Dermal treatment group:
The major part of all the dermal doses (> 90% of the dose recovered) in both high and low dose treatment groups was found in the dose wash, dose site and dose site wrappings.
Details on distribution in tissues:
- Intravenous dose group:
Little or no radioactivity was observed in the kidney and bladder tissue.
- Dermal treatment group:
Little or no radioactivity was observed in the kidney and bladder tissue.
Details on excretion:
- Intravenous dose group:
The primary route of excretion is via the urine and the portion of the administered dose excreted via the kidneys was about 80% and that found in the feces was only 2 to 3%. The majority of urinary excretion occurred during the first 6 h after dosing.
- Dermal treatment group:
< 1% of dose was found in the urine and feces of the high dermal dose group and that expected in the urine and feces in the low dermal dose group ranged from about 2.5% to 6.6% of dose.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
When administered by intravenous injection radiolabelled tributyl phosphate (TBP) is rapidly eliminated from the body of Yucatan minipigs via the urine. Dermal applications of radiolabelled TBP are poorly absorbed in the minipig in both high and low dose levels. On average, about 3 to 4% of the low dose appeared in the urine and feces whereas less than 1% of the high dose appeared in the excreta. Radiolabelled TBP did not appear to bioaccumulate in the bladder or kidney tissue of Yucatan minipigs.
Executive summary:

Radiolabeled 14C-Tributyl phosphate was administered to Yucatan minipigs by intravenous and dermal dose routes in order to investigate its absorption, distribution, and excretion in this species. Measurements of radioactivity were made in samples of feces, urine, bladder and kidney following intravenous and dermal application. Radioactive material was recovered at more than 80% for all dose groups except the low dose dermal groups where about 60% was recovered. 14C-TBP was rapidely eliminated via the urine and within the first 6 hr of intravenous exposure. The dermal doses were very poorly absorbed (maximum amount absorbed was about 5% of dose) and it was again eliminated mostly via the urine. There were no apparent sex differences in this study.