4-chlorotoluene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: short description but provides sufficient information to be taken into account

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Effects of p-chlorotoluene on rat lung and liver benzo(a)pyrene metabolism and microsomal membrane structure and function

Author:

Zewdie T, Silverman DM, Schatz RA

Year:

1997

Bibliographic source:

J Toxicol Environm Health 50, 159-172

Reference 2

Reference Type:

publication

Title:

The influence of time and dose on the development of p-chlorotoluene (PCT) induced changes in rat liver and lung cytochrome P450 system and Benzo(a)pyrene(BaP) metablolism

Author:

Zewdie T, Silverman D, Schatz R

Year:

1991

Bibliographic source:

The Toxicologist 11(1), 319 (abstr.)

Materials and methods

Objective of study:

distribution

Principles of method if other than guideline:

Male Sprague-Dawley rats weighing 200-225 g (Charles River Breeding Labs, Willmington, MA) were maintained on tap water and standard lab feed ad libitum in a 12-h light-dark cycle for 3 d prior to treatment. PCT, 0.5, 1, or 1.5 g/kg, was administered to rats in preservative-free soybean oil (4 ml/kg, ip). Controls were given preservative- free soybean oil only (4 ml/kg, ip). Animals were killed by cervical dislocation 1, 4, or 12 h after solvent injection. Lungs and livers were perfused in situ with 0.9% saline (25°C) until lungs were pink to white in color. All tissues were stored at -80°C for a maximum of 2 wk.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorotoluene

EC Number:

203-397-0

EC Name:

4-chlorotoluene

Cas Number:

106-43-4

Molecular formula:

C7H7Cl

IUPAC Name:

4-chlorotoluene

Details on test material:

p-chlorotoluene, purity: 98 %

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

soya oil

Duration and frequency of treatment / exposure:

single application

Doses / concentrations

Remarks:

Doses / Concentrations:
Males: 0, 500, 1000, 1500 mg/kg bw in soybean oil

No. of animals per sex per dose / concentration:

no data

Control animals:

not specified

Results and discussion

Preliminary studies:

no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:

no data

Details on distribution in tissues:

no data

Details on excretion:

no data

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

no data

Any other information on results incl. tables

When PCT (1 g/kg, ip) was given to rats, blood and lung levels rose rapidly 
at 1 h and, for the time points tested, reached near maximal values at 4 h. 
Liver levels reached maximum levels at 1 h and started to  decline at 4 h. 
Lowest solvent tissue levels were observed at 12 h.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results

Executive summary:

Male Sprague-Dawley rats weighing 200-225 g were maintained on tap water and standard lab feed ad libitum in a 12-h light-dark cycle for 3 d prior to treatment. PCT, 0.5, 1, or 1.5 g/kg, was administered to rats in preservative-free soybean oil (4 ml/kg, ip). Animals were killed by cervical dislocation 1, 4, or 12 h after solvent injection. Lungs and livers were perfused in situ with 0.9% saline (25°C) until lungs were pink to white in colorand, PCT concentrationsin lungs and livers were measured.

When PCT (1 g/kg, ip) was given to rats, blood and lung levels rose rapidly at 1 h and, for the time points tested, reached near maximal values at 4 h.Liver levels reached maximum levels at 1 h and started to  decline at 4 h.Lowest solvent tissue levels were observed at 12 h.