Registration Dossier

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: sufficiently documented literature data which is comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
only one dose level per route tested
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chlorobenzaldehyde
EC Number:
201-956-3
EC Name:
2-chlorobenzaldehyde
Cas Number:
89-98-5
Molecular formula:
C7H5ClO
IUPAC Name:
2-chlorobenzaldehyde
Details on test material:
- Name of test material (as cited in study report): 2-chlorobenzaldehyde
- Radiochemical purity (if radiolabelling): at least 98%
- Specific activity (if radiolabelling): 20 mCi/mmol; reduced to 0.275 mCi/mmol by addition of pure unlabelled material
- Locations of the label (if radiolabelling): carbonyl-group
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TNO, Zeist (The Netherlands)
- Age at study initiation: about 6 weeks
- Individual metabolism cages: yes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least three days prior to experiments rats were housed in individual glass metabolism cages

ENVIRONMENTAL CONDITIONS
- Air changes: Air was drawn through the metabolism cage (volume 24 l) at a rate of 400 ml/min; pressure inside the cage was somewhat lower than outside.


OTHER INFORMATION
- polyethylene catheters (I.D. 0.4 mm; O.D. 0.8 mm) were placed into the femoral artery and the jugular vein and led subcutaneously to the nuchal area where they went out of the body

Administration / exposure

Route of administration:
other: intravenous or intraperitoneal
Vehicle:
water
Details on exposure:
25 µl/kg bw of the radiolabelled test substance (specific radioactivity 1.83 mCi/ml dissolved in 1 ml of 2% aqueous solution of Tween-60) were injected into the jugular vein catheter, duration about 4 minutes; 37.5 µl/kg were applied intraperitoneally
Duration and frequency of treatment / exposure:
single application
Doses / concentrations
Remarks:
Doses / Concentrations:
intravenous application: 25 µl/kg

intraperitoneal application: 37.5 µl/kg
No. of animals per sex per dose / concentration:
intravenous application: 6

intraperitoneal application: 2
Control animals:
no
Details on dosing and sampling:
Urine, faeces and gas-washing bottle samples containing expired 14CO2 were collected over a 24 hour experimental period.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
After intravenous or intraperitoneal application of the test substance, the radioactivity in plasma declined in a bi-exponential fashion over a period of 24 hours. Plasma radioactivity time profiles were very similar afterintravenous or intraperitonea dosing. The first elimination phase with a 14C-half life of 15.6 minutes was followed by a slower second one. No radioactivity was retained in the red blood cells.

The test item was mainly excreted via urine, only small amounts were found in the faeces and in the exhaled air. Excretion was complete (> 99%) within 24 hours, the majority of the radioactivity (about 90%) was recovered in the 0-6 h urine.
Toxicokinetic parameters
Toxicokinetic parameters:
half-life 1st: 15.6 minutes

Any other information on results incl. tables

Percent of administered radioactivity after intravenous or intraperitoneal administration in rats (means +/- SD)

   intravenous (n=6)  intraperitoneal (n=2)
 Dose (µl/kg)  25  37.5
 Urine    
   0 -6 h  88.7 +/- 4.59  95.8 +/- 0.71
  6 -24 h  8.8 +/- 2.33  6.0 +/- 0.28
 Total Urine  97.5 +/- 3.57  101.8 +/- 0.99
 Faeces Total  2.2 +/- 0.91  2.4 +/- 0.14
 14CO2 Total (Exhaled)  0.4 +/- 0.32  0.3 +/- 0.0
 Recovery  100.1 +/- 3.56  104.5 +/- 0.85

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Regarding the results of the study, the test substance 2-chlorobenzaldehyde is rapidly and completely eliminated within 24 hours after intravenous or intraperitoneal application to rats. Excretion is mainly via urine.

Categories Display