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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study, available as unpublished report, no restrictions, adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
Other: Monsanto Company internal method.
Study conducted in general accordance with GLP Standards with the following exceptions:
- The stability of the test substance, neat and after mixing with carrier, was not determined; however stability can be inferred from Benzene, mono-C10-13-alkyl derivs., distn. residues studies.
- Characterization of the test substance was not conducted according to the standards.
- Characterization and stability data for reference substances were not developed according to the standards.
These deviations should not impact the interpretation of the study.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: approximately seven to ten weeks of age
- Weight at study initiation: 200-350 gm
- Housing: one per cage
- Diet (e.g. ad libitum): ad libitum (Purina Certified (#5002) Laboratory Rodent Chow )
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least ten days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72+2 °F
- Humidity (%): 35-60%
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Rats were gavaged using a 2 mL syringe fitted with a straight Perfectum 16 or 18 gauge, 2-inch animal feeding needle (Popper and Sons, inc., New Hyde Park, NY). The dose was contained in approximately 1.1-1.6 mL of solution.

VEHICLE
- Concentration in vehicle: 65.2 mg/g



Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Dose / conc.:
300 mg/kg bw/day
No. of animals per sex per dose:
Nine male rats per dose level
Control animals:
not specified
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, liver, kidney, intestinal contents and carcasses

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption was not determined in this study. However, the minimum amount absorbed, calculated as the amount of radioactivity excreted in the urine plus the amount of radioactivity in the organs and carcass, was approximately 31.9% (normalized data) of the administered dose 8 hours after gavage.
Details on distribution in tissues:
The gut contents, followed by the carcass and liver, contained the majority of hydrogenated terphenyl derived radioactivity 8 hours after administration. Within 48 hours the radioactivity in the gut contents had declined by a factor of 10, while the radioactivity in the feces had increased, suggesting that most of the material in the feces was composed of unabsorbed parent compound.
Based on a per gram concentration basis, greater than 1% of the dose/per gram of gastrointestinal contents was detected in the gut 8 hours after gavage. Although almost ten times more material was observed in the carcass compared to the liver there was little difference when the % dose was expressed as per gram of tissue (0.22 and 0.37% administered dose/gram, respectively, liver and carcass). The large proportion of dose in the carcass was due to its larger mass compared to the liver.
Details on excretion:
The greatest amount of radioactivity was found in the intestinal contents 8 hours after an oral dose of hydrogenated terphenyl at 300 mg/kg, with the faces representing the major route of elimination. After 48 hours the amount detected in the feces had increased to approximately 75% of the administered dose and at 168 hours greater than 85% of the dose had been excreted by fecal elimination. Approximately 11 % of the administered dose was excreted in the urine over the 168 hour observation period.
Elimination of hydrogenated terphenyl derived radioactivity best fit a 1 compartment model. The half-lives for elimination via the urine and feces were estimated to be 23.0 and 13.0 hours, respectively. The whole body elimination reflected that of the feces and the half-life was estimated to be 14.0 hours.

Any other information on results incl. tables

Liver and kidney weights liver weights were significantly increased above control liver weights only in animals administered 300 mg/kg of hydrogenated terphenyl.

The test material was not readily absorbed and did not appear to accumulate in rat body tissues following a single gavage dose of 300 mg/kg.  Very little radiolabel was evident in the kidney and liver 48 hours after gavage. Generally the test material appeared to have little effect on AHH or ECOD activity following single exposure, although some statistically significant changes in enzymatic activity were noted.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: no bioaccumulation potential based on study results
Hydrogenated terphenyl was not readily absorbed and did not appear to accumulate in body tissues following a single gavage of 300 mglkg. The fecal half-life was about 13 hours and the urinary half-life was about 23 hours. The whole body half-life was estimated to be about 14 hours and the primary route of elimination was via the feces. Very little radiolabel was evident in the kidney and liver 48 hours after gavage and little enzyrne induction was noted in these tissues.

Executive summary:

Hydrogenated terphenyl was not readily absorbed and did not appear to accumulate in body tissues following a single gavage of 300 mg/kg in male rats. The fecal half-life was about 13 hours and the urinary half-life was about 23 hours. The whole body half-life was estimated to be about 14 hours and the primary route of elimination was via the feces. Very little radiolabel was evident in the kidney and liver 48 hours after gavage and little enzyrne induction was noted in these tissues.