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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Excretion study which provides scientific valid information.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985

Materials and methods

Objective of study:
excretion
Principles of method if other than guideline:
A single po dose of trichloro[2-14C]acetic acid (75 mg/kg; 9 µCi) was given to a single male Osborne-Mendel rat as a solution in water (5 mL/kg). Urine, feces and expired air were collected for 24 hours and total radioactivity in excreta was measured.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trichloroacetic acid
- Analytical purity: > 99 %
Radiolabelling:
yes
Remarks:
Trichloro[2-14C]acetic acid, 9 mCi/mmol ( 99% purity)

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: All of the animals were bred at Imperial Chemical Industries PLC Breeding Unit at Alderley Park.
- Weight at study initiation: 180-200 g
- Fasting period before study: No
- Housing: The animals were housed in glass metabolism cages (Jencons, Hemel Hempstead, Herts, UK) designed for the separate collection of urine, feces, and expired air.
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Feed (PCD diet, Special Diet Services Ltd, Witham, Essex, UK) was provided ad ibitum before and during the experiments.
- Water (e.g. ad libitum): Water was provided ad ibitum before and during the experiments.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animals were housed in temperature-controlled rooms (22 ºC)
- Photoperiod (hrs dark / hrs light): 12-hr lighting cycle

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: A solution in water (5 mL/kg)
Duration and frequency of treatment / exposure:
A single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
A single dose of trichloro[2-14C]acetic acid (75 mg/kg; 9 µCi)
No. of animals per sex per dose:
1 male rat per dose
Control animals:
not specified
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces and expired air.
- Time and frequency of sampling: Urine and feces were collected at -70 ºC for 24 hr; expired air was coIlected for 24 hr.
- From how many animals: All animals
- Method type(s) for identification:
Expired air:
Air was drawn through the cages at a rate of 500 mL/min. Expired trichloroacetic acid and organic metabolites were collected in hexane traps (3 x 50 mL) at -70 ºC, exhaled CO2 in traps containing 2 N sodium hydroxide solution (2 x 500 mL). After CO2 had been removed the expired air was passed over a Hopcalite catalyst in order to convert expired carbon monoxide to CO2 which was collected in two further traps containing sodium hydroxide solution. The traps were not changed during the 24-hr period of collection.
The hexane traps used to collect expired air from treated animals were analyzed by gas chromatography in a Pye Series 104 instrument fitted with both flame ionization and radiochemical detectors (ESI Nuclear 504 Radiogas Detector). A 1.7-m x 2-mm glass column packed with 0.2% Carbowax 1500 on 80- to 100-mesh Carbopack C was operated at 120 ºC with an Argon/CO2 (95:5 v/v) carrier gas flow of 20 mL/min. The effluent from the column was split equally between the two detectors. RadioIabeled mass peaks in the chromatogram were identified by gas chromatography-mass spectrometry (GC-MS) in an LKB 2091 EI/CI instrument fitted with the same chromatography column and operated at the same temperature.
Urine:
For the qualitative analysis of urinary metabolites, 0- to 24-hr urine samples were acidified to pH 1 with 1 M sulfuric acid and extracted with two vol of
diethyl ether. The extracts were concentrated (1 mI), methylated with an ethereal solution of diazomethane, and analyzed by gas chromatography and GC-MS. In this case a 0.9-m x 2-mm glass column packed with 20% OV101/0.1% Carbowax 1500 on 100- to 120-mesh Supelcoport was used at 80°C.The residual urine was concentrated under reduced pressure at 30°C and chromatographed on a 20-cm X 8-mm high-pressure liquid chromatography column packed with 10 µm Lichrosorb RP8 silica. The eluting solvent consisted of a linear gradient from 1 % v/v acetic acid in water to 1% v/v acetic acid in methanoI over 30 min at a flow rate of 4 mL/min. Fractions of 4 mL were collected and the radioactivity in an aliquot of each fraction was
determined by liquid scintillation counting. Fractions containing radioactivity were evaporated to dryness under reduced pressure and the trimethylsilyl derivatives prepared with BSTFA in pyridine at 70 ºC for 18 hr. The derivatized fractions were analyzed by GC and GC-MS on a 0.9m X 2-mm glass column packed with 6.5% OV101 on 100- to 120-mesh Supelcoport and operated at 170 ºC.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
In this experiment, rats dosed po with trichloro[2-14C]acetic acid (75 mg/kg) were found to excrete 7.2% of the dose as 14-C02 in 24 hr. Over the same period, 58.7% of the dose was excreted in urine and 1 % in feces.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
14-C02

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: The urine was the main excretion route in rats.
In this experiment, rats dosed po with trichloro[2-14C]acetic acid (75 mg/kg) were found to excrete 7.2% of the dose as 14-C02 in 24 hr, 58.7% of the dose was excreted in urine and 1 % in feces.
Executive summary:

The excretion of trichloroacetic acid has been studied in rats. A single po dose of trichloro[2-14C]acetic acid (75 mg/kg; 9 µCi)

was given to a single male Osborne-Mendel rat as a solution in water (5 mL/kg). Urine, feces and expired air were collected for 24 hours and total radioactivity in excreta was measured. In this experiment, rats were found to excrete 7.2% of the dose as 14-C02 in 24 hr. Over the same period, 58.7% of the dose was excreted in urine and 1 % in feces.