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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other: GLP-compliant study, available as unpublished report, no restrictions, adequate for assessment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:
other: liver and kidney enzyme analysis
Principles of method if other than guideline:
Other: Monsanto Company internal method.
Study conducted in general accordance with GLP Standards with the following exceptions:
- Concentration and homogeneity in carrier were not determined for total test substance for Group 1.
- 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
Details on test material:
- Physical state: clear yellow oily liquid
- Purity: 98.5%
- Expiration date of the lot/batch: 10/89
- Storage condition of test material: room temperature
Radiolabelling:
no

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
- Amount of vehicle (if gavage): dosing volume of 5 mL/kg




Duration and frequency of treatment / exposure:
single dose, sacrificed 48 hours after dosing
Doses / concentrations
Remarks:
Doses / Concentrations:
0,100, or 300 mg/kg body weight
No. of animals per sex per dose:
Five male rats per dose level
Control animals:
yes
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

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.

Aryl Hydrocarbon Hydroxylase Analysis: Hydrogenated terphenyl had little effect on hepatic AHH activity when administered to male rats by gavage. Although a slight increase in induction was observed in animals administered 300 mg/kg, this was not found to be statistically significant from animals administered either 0 or 100 mg/kg.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Liver weights were significantly increased above control liver weights only in animals administered 300 mg/kg of hydrogenated terphenyl. Hydrogenated terphenyl had little effect on hepatic Aryl Hydrocarbon Hydroxylase activity when administered to male rats by gavage. Although a slight increase in induction was observed in animals administered 300 mg/kg, this was not found to be statistically significant in animals administered either 0 or 100 mg/kg.
Executive summary:

The effects of on liver and kidney microsomal drug-metabolizing enzymes were studied following oral administration. Hydrogenated terphenyl was administered to male Sprague Dawley rats a single oral dose at 0,100 and 300 mg/kg body weight. Ethoxycoumarin-o-deethylase (ECOD) and aryl hydrocarbon hydroxylase (AHH) activities were determined in liver and kidney S-9 preparations. Hydrogenated terphenyl did not appear to be extensively absorbed after a single oral dose of 300 mg/kg (30%). Liver weights were significantly increased above control liver weights only in animals administered 300 mg/kg of hydrogenated terphenyl. Hydrogenated terphenyl had little effect on hepatic Aryl Hydrocarbon Hydroxylase activity when administered to male rats by gavage. Although a slight increase in induction was observed in animals administered 300 mg/kg, this was not found to be statistically significant from animals administered either 0 or 100 mg/kg.