1,2-dichloropropane

Basic toxicokinetics

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

1,2-dichloropropane

EC Number:

201-152-2

EC Name:

1,2-dichloropropane

Cas Number:

78-87-5

Molecular formula:

C3H6Cl2

IUPAC Name:

1,2-dichloropropane

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 or test system 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 / concentration:

First experiment: 6 males, 6 females
Second experiment: 5 females

Control animals:

no

Positive control reference chemical:

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.