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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
Study period:
Initiation date: 24 August 1988, Termination date: 10 October 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Objective of study:
other: assessment of radioactive residues in ruminant tissues, organs and milk following daily dosing of 14C-CGA154281 to dairy goats
Test guideline
Qualifier:
according to
Guideline:
other: EPA Pesticide Assessment Guidelines, Subdivision O: series 171-4
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
other: goat
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: At least 2 years
- Weight at study initiation: 34-44 kg
- Fasting period before study: No
- Housing: Individually
- Individual metabolism cages: yes
- Diet: Daily ration of 1.0 kg hay and 1.0 kg of Sweet Goat Feed "B" divided into two and half given at each milking (am and pm)
- Water: Water ad libitum
- Acclimation period: 6 days (acclimatised to metabolism cages and the balling gun 2 days prior to dosing)

ENVIRONMENTAL CONDITIONS
- Temperature: 60-80°F
- Humidity: 54-100%
- Air changes (per hr): Not reported
- Photoperiod: Natural light/dark cycles

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:
oral: capsule
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING CAPSULES: The phenyl 14C-CGA154281 was already contained within the gelatin capsules when supplied

HOMOGENEITY AND STABILITY OF TEST MATERIAL: Characterisation and stability of the test material was the responsibility of the sponsor and is not reported.
Duration and frequency of treatment / exposure:
up to 28 days (+ 3 day recovery)
Doses / concentrations
Remarks:
Doses / Concentrations:
0.09 mg (equivalent to 0.045 ppm in the feed (2 kg/day).
No. of animals per sex per dose:
1
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Milk, tissues (tenderloin, round muscle, peripheral fat, omental fat, liver, kidneys), blood.
- Time and frequency of sampling: Milk twice daily (am and pm), blood and tissues at sacrifice
- Limits of detection and quantification: <0.0001 ppm (milk), <0.002 ppm (tissues)
Statistics:
Not applicable

Results and discussion

Main ADME results
Type:
other: radiocarbon residues
Results:
Residue levels in milk were below detection limit of <0.0001 ppm except day 5 and 7 samples from the goat dosed for 7 days. No radiocarbon residues were measured in any of the tissues sampled post mortem.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Radiocarbon residue levels in milk were all below the detection limit of <0.0001 ppm except day 5 and 7 samples from the goat dosed for 7 days (0.0002 ppm each). These very low residue levels represented an average of 19 dpm/mL. No radiocarbon residues were measured in any of the tissue or organ samples collected post mortem, as measured at <0.002 ppm detection limit.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Residue levels in milk were below detection limit of <0.0001 ppm except day 5 and 7 samples from the goat dosed for 7 days (where residues of 0.0002 ppm were detected). No radiocarbon residues were measured in any of the tissues sampled post mortem.
Executive summary:

This study was performed to assess the radiocarbon residues in ruminant tissues organs, and milk resulting from the daily administration of 14C-CGA154281 to dairy goats.

Five lactating goats received a daily radiocarbon dose of 0.09 mg 14C-CGA154218 (equivalent to 0.045 ppm in feed) for up to 28 days. The 14C-CGA154281 dose corresponded to 2.33 µg/kg body weight. The animals were killed approximately 20 h after the final dose. One animal each was dosed for 7, 14, 21, and 28 days, and one animal was dosed for 28 days followed by a 3 day withdrawal from dosing. At necropsy, representative samples of round muscle, tenderloin muscle, liver, kidneys, omental fat, peripheral fat, and blood were collected and frozen.

Milk was collected twice daily (am and pm) and measured. Milk samples were taken pre-dose and on days 1, 3, 5, 7, 14, 21, and 28 and on days 1 and 3 of withdrawal from 28 days dosing. The pm milk was mixed with the following am milk for each sample period.

All tissue samples were homogenized with dry ice, combusted and quantitated by liquid scintillation counting. Milk samples were homogenized by shaking and were quantitated directly in liquid scintillation cocktail. The blood was homogenized by repetitive hand inversion of the bottle, combusted and quantitated.

Residue levels in milk were below detection limit of <0.0001 ppm except day 5 and 7 samples from the goat dosed for 7 days (where residues of 0.0002 ppm were detected). No radiocarbon residues were measured in any of the tissues sampled post mortem.