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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-12-16 To: 1989-01-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted in methods comparable to OECD guideline 417 " Toxicokinetics" and under GLP. However, only one dose level was tested.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Objective of study:
absorption
distribution
excretion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
See rationale for reliability above.
Principles of method if other than guideline:
N/A
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N-Tridecyl-N, N-Dimethylhydroxyethyleneammonium chloride
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: Active
- Physical state: liquid
Radiolabelling:
yes
Remarks:
Carbon 14

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
- Source: Charles River Ltd.
- Age at study initiation: 7 weeks
- Weight at study initiation: ca. 200 g
- Fasting period before study: overnight and 4 hours after dosing
- Housing: individual metabolism cages
- Individual metabolism cages: yes
- Diet: ad libitum except for during dosing, LAD 1, Labsuro, Manea, UK)
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): N/A
- Humidity (%):N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): N/A


IN-LIFE DATES: From: 1989-12-18 To: 1989-12-21

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The test material was dissolved in distilled water (ca. 4.5 ml). The specific activity of the dose solution was measured, and the dose solution was diluted with distilled water to a concentration of 41651222 dpm/g (ca. 1.0 mg/g; 18.8 µCi/g).


DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A


VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Concentration in vehicle: N/A
- Amount of vehicle (if gavage): 4.5 ml
- Lot/batch no. (if required): N/A
- Purity: N/A
Duration and frequency of treatment / exposure:
72 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/kg bw
No. of animals per sex per dose:
4 male rats used for experiment
Control animals:
not specified
Positive control:
N/A
Details on study design:
- Dose selection rationale: N/A
- Rationale for animal assignment (if not random): N/A
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, feces, blood, expired air, tissues, and cage washes
- Time and frequency of sampling: feces were collected during 24-hr intervals after dosing up to 72 hours. Urine was collected in solid CO2-cooled containers during 24-hr intervals after dosing upto 72 hours. Expired air was passed through CO2-traps (two per animal). Cage washing were collected at 24 and 48 hours after dosing. The final cage wash was made at 72 hours.
- Other: the following tissues were examined for radioactivity: liver, gastro-intestinal tract, pancreas, adipose tissue, kidneys, muscle, heart, spleen, testes, bone marrow, bone (femurs), muscle (hind-limb , right), and lungs, and remaining carcass. Organs with internal cavities were cut open to remove contents and washed. Bladder washings were aded to the urine, and blood from the heart was discarded. The bone marrow was removed from both femurs. The femurs were washed with distilled water and the washings discarded.
Samples of tissues (finely minced, homogenized) prior to cumbustion . Smaller organs (heart, lungs,spleen, pancreas) were combusted in toto. Tisses, fecal residues, and whole blood were combusted and the products absorbed into Optisorb 1 and mixed with Optisorb S scintillator system. Samples of expired air, fecal extracts, urine, cage washings, and carcass digest were mixed with a psuedo-cumene based scintillation system. Radioactivity was measured with a liquid scintillation counter with automatic standard quench correction. Radioactivity in the amounts of less than twice background was considered to be below the level of accurate measurement.

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): N/A
- Time and frequency of sampling: N/A
- From how many animals: (samples pooled or not) N/A
- Method type(s) for identification: N/A
- Limits of detection and quantification: N/A
- Other: N/A

TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): N/A
Statistics:
N/A

Results and discussion

Preliminary studies:
N/A

Toxicokinetic / pharmacokinetic studies

Details on absorption:
N/A
Details on distribution in tissues:
The greatest mean concentrations of radioactivity were detected in the liver (0.935 µg/g), and gastro-intestinal tract (0.527 µg/g). Concentrations of radioactivity were 0.166, 0.203, and 0.254 µg/g in the pancreas, fat and kidneys, respectively. Concentrations in the muscle, heart, spleen, and lungs were between 0.083 and 0.092 µg/g. The lowest detectable concentrations were in the testes (0.033 µg/g) and the whole blood (0.024 µg/g). Concentrations of radioactivity in the bone, bone marrow and brain were below the limits of accurate measurement (<0.064, <0.299 and < 0.027 µg/g, respectively).
Transfer into organs
Transfer type:
other: N/A
Observation:
not determined
Details on excretion:
85.94% of the dose was excreted in the feces, the majority (83.84% dose) being excreted in the first 48 hours after dosing.
Excretion of radioactivity in the urine and expired air (13.28%) and retention of radioactivity in tissues (0.30% dose, excluding gastro-intestinal tract and contents) indicated that the compound was poorly absorbed when administered by the oral route. The concentration of radioactivity in the tissues (maximum 0.94 µg/g in the liver) at 72 hours also were indicative of a low proportion of the dose being absorbed.
Toxicokinetic parameters
Toxicokinetic parameters:
other: N/A

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
N/A

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
During the 0-72 hours after dosing of 50 mg/kg of the test substance by gavage, urine, feces, expired air, and cage washings accounted for means of 12.77, 85.94, 0.42, and 0.515% dose, respectively. Tissues contained a mean of 1.17% at 72 hours. This low concentration of radioactivity in the tissues (maximum 0.94 µg/g in the liver) at 72 hours is indicative of the low proportion of the dose being absorbed.
Executive summary:

The absorption, distribution and excretion of the test material have been studied in male CD rats after oral administration of the carbon-14 compound at a dose level of 50 mg/kg. During the study, rats were housed individually in metabolism cages. Faeces were collected during 24 hour intervals, up to 72 hours. Urine was collected in CO2 cooled containers during 24 hour intervals, up to 72 hours. Expired air was passed through CO2 traps. The traps were changed every 24 hours up to 72 hours. Cage washings were collected at 24, 48 and 72 hours. On sacrifice, and bladder urine was added to the 72 hour urine sample. The rats were sacrificed at 72 hours. A blood sample was taken prior to sacrifice. After sacrifice, tissues were taken from the carcass, and processed to determine radioactive activity.

Radioactivity was measured in all fluid samples and combusted tissue homogenates using a liquid scintillation counter. Radioactivity in amounts of less than twice background was considered to be below the level of accurate measurement.

During 0 -72 hours after dosing, urine, feces, expired air and cage washings accounted for means of 12.77, 85.94, 0.42 and 0.51% dose, respectively. Tissues contained a mean of 1.17% dose at 72 hours, with the highest dose being identified in the liver (0.935 ug/g). The radioactive activity was below the relative limits of detection in the bone, bone marrow and brain.

The highest mean concentrations of radioactivity were detected in liver (0.254 µg/g), fat (0.203 µg/g), and the pancreas (0.166 µg/g). The lowest concentrations were detected in testes (0.033 µg/g) and Whole blood (0.024 µg/g), and concentrations in bone marrow, bone, and brain were below their relative limits of detection. Other tissues (heart, lungs, muscle, and spleen) obtained between 0.083 and 0.092 µg/g.

During the 0-72 hours after dosing of 50 mg/kg of the test substance by gavage, urine, feces, expired air, and cage washings accounted for means of 12.77, 85.94, 0.42, and 0.515% dose, respectively. Tissues contained a mean of 1.17% at 72 hours. This low concentration of radioactivity in the tissues (maximum 0.94 µg/g in the liver) at 72 hours is indicative of the low proportion of the dose being absorbed.