Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published in the peer-reviewed literature.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
The Excretion and Retention of Components of the Soil Fumigant D-D and their metabolites in the rat
Author:
Hutson, D.H. et al.
Year:
1971
Bibliographic source:
Food Cosmet. Toxicol. 9, 677 - 680

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The rates, routes of excretion and the retention of radioactivity were measured after seperate oral administration of 14C-labelled 1,2-Dichloropropane
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2-Dichloropropane
- Physical state: liquid
- Radiochemical purity (if radiolabelling): > 99% by preparative gas-liquid chromatography
- Specific activity (if radiolabelling): 1.09 mc/m-mole
- Other: synthesized at Woodstock Agricultural Research Center, Sittingbourne
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: Carworth Farm E
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: bred at testing facility (Shell Research Limited, Sittingbourne, Kent, England)
- Age at study initiation: no data
- Weight at study initiation: 200-250 g
- Fasting period before study: not specified
- Housing: housed in glass metabolism cages (Jencons "Metabowls") for urinary excetion studies, and Quickfir Industrial Pipe for respiratory studies
- Individual metabolism cages: yes (urine), no (exhaled metabolites)
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): not specified
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): under standard conditions
- Humidity (%): under standard conditions
- Air changes (per hr): under standard conditions
- Photoperiod (hrs dark / hrs light): under standard conditions
- Animals maintained under specific pathogen free conditions were used for the study

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Each animal (6 rats/sex) was dosed by stomach tube with 1,2-Dichloro(14C)propane (0.88 mg, 8.5 µC), administered as a solution in 0.5 ml arachis oil. In another experiment, each animal (5 female rats) was dosed orally with 10.3 µC (1.07 mg) 1,2-Dichloro(14C)propane

VEHICLE
- Justification for use and choice of vehicle (if other than water): recommended by regulatory agencies
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): 0.5 ml
- Lot/batch no. (if required): not specified
- Purity: not specified

HOMOGENEITY AND STABILITY OF TEST MATERIAL: no data
Duration and frequency of treatment / exposure:
single administrations
Doses / concentrations
Remarks:
Doses / Concentrations:
First experiment: 0.88 mg (8.5 µC) administered as a solution in 0.5 ml arachis oil.
Second experiment: 1.07 mg (10.3 µC).
No. of animals per sex per dose:
First experiment: 6 males, 6 females
Second experiment: 5 females
Control animals:
no
Positive control:
not applicable
Details on study design:
Experiment 1 - Six rats of each sex were dosed by stomach tube with 1,2-Dichloro(14C)propane (0.88 mg, 8.5 µC), administered as a solution in 0.5 ml arachis oil and housed in glass metabolism cages (Jencons Metabowls). After 4 days the animals were killed and the radioactivity in the skin, alimentary tract and remaining carcass were measured by a combustion technique.

Experiment 2 - In this experiment (14C) Carbon dioxide and other radioactive compounds exhaled after oral administration were determined, Five female were dosed orally with 10.3 µC (1.07 mg) 1,2-Dichloro(14C)propane and placed in an 18 inch length of 4 inch diameter Quickfit Industrial Pipe fitted with a stainless steel wire-mesh frame dividing the pipe into an individual section for each animal. Food and water were supplied. Air was drawn at 650 ml/min through the tube containing the animals and then through 5 traps, the first being a water-condensing trap at -20 °C, followed by two gas scrubbers containing toluene at -20 °C and two gas scrubbers containing 5N-sodium hydroxide solutions

Radioactivity in urine and in the toluene traps was measured directly by scintillation counting by adding an aliquot to the scintillator solution. Fecal and tissue samples were combusted to carbon dioxide, which was absorbed in the scintillator solution. Carbon dioxide was released from the sodium hydroxide traps by acidification and was absorbed in the basic scintillator solution for radioassay
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, gut, skin, carcass, exhaled air
- Time and frequency of sampling: 4 days
Statistics:
standard descriptive statistics were used

Results and discussion

Preliminary studies:
not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
not applicable
Details on distribution in tissues:
Ninety-six hours after the administration of 0.88 mg [14C]1,2-Dichloropropane/ animal, Carworth Farm rats (6 animals/sex) were dissected and 0.5 % of the radioactivity was still present in the intestinal tract, 1.7 %(male) and 1.4 % (female) in the skin and 4.1 % (male) and 3.2 % (female) in the remainder of the body.

Details on excretion:
Ninety-six hours after the administration of 0.88 mg [14C]1,2-dichloropropane/animal, Carworth Farm rats (6 animals/sex) were dissected and 51.1 % (male) and 54.4 % (female) of the radioactivity eliminated with urination, 6.8 % (male) and 4.9 % (female) was eliminated with faeces. After administering the above-mentioned dosage to females (n = 5), within 96 hours, the exhalation was 19.3 % of radioactivity in the form of CO2 and 23.1 % as non-identified evaporable substances.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
not applicable

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
Based on the results of the study, 1,2-Dichloropropane appears to have low potential for bioaccumulation
Executive summary:

In this study - Experiment 1 - Six rats of each sex were dosed by stomach tube with 1,2-Dichloro(14C)propane (0.88 mg, 8.5 µC), administered as a solution in 0.5 ml arachis oil and housed in glass metabolism cages (Jencons Metabowls). After 4 days the animals were killed and the radioactivity in the skin, alimentary tract and remaining carcass were measured by a combustion technique.

Experiment 2 - In this experiment (14C) Carbon dioxide and other radioactive compounds exhaled after oral administration were determined, Five female were dosed orally with 10.3 µC (1.07 mg) 1,2-Dichloro(14C)propane and placed in an 18 inch length of 4 inch diameter Quickfit Industrial Pipe fitted with a stainless steel wire-mesh frame dividing the pipe into an individual section for each animal. Food and water were supplied. Air was drawn at 650 ml/min through the tube containing the animals and then through 5 traps, the first being a water-condensing trap at -20 °C, followed by two gas scrubbers containing toluene at -20 °C and two gas scrubbers containing 5N-sodium hydroxide solutions

Radioactivity in urine and in the toluene traps was measured directly by scintillation counting by adding an aliquot to the scintillator solution. Fecal and tissue samples were combusted to carbon dioxide, which was absorbed in the scintillator solution. Carbon dioxide was released from the sodium hydroxide traps by acidification and was absorbed in the basic scintillator solution for radioassay

Ninety-six hours after the administration of 0.88 mg [14C]1,2-Dichloropropane/ animal, Carworth Farm rats (6 animals/sex) were dissected and 0.5 % of the radioactivity was still present in the intestinal tract, 1.7 %(male) and 1.4 % (female) in the skin and 4.1 % (male) and 3.2 % (female) in the remainder of the body.

Ninety-six hours after the administration of 0.88 mg [14C]1,2-dichloropropane/animal, Carworth Farm rats (6 animals/sex) were dissected and 51.1 % (male) and 54.4 % (female) of the radioactivity eliminated with urination, 6.8 % (male) and 4.9 % (female) was eliminated with faeces. After administering the above-mentioned dosage to females (n = 5), within 96 hours, the exhalation was 19.3 % of radioactivity in the form of CO2 and 23.1 % as non-identified evaporable substances.