1,2,4-trichlorobenzene

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented publication which meets basic scientific principles

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Repeated Topical Applications of 1,2,4-Trichlorobenzene

Author:

Powers MB, Coate WB, Lewis TR

Year:

1975

Bibliographic source:

Arch Environ Health 30: 165-167.

Materials and methods

Principles of method if other than guideline:

Increasing concentrations of 1,2,4-trichlorobenzene were applied topically to the ventral surface of the rabbit ear three times weekly for 13 weeks.
Additional groups of rabbits received similar treatment with petroleum ether (solvent controls), received no treatment (negative controls), and received four once-weekly treatments with hexachlorodiphenyloxide, a known chloracnegenic agent (positive controls)

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2,4-trichlorobenzene

EC Number:

204-428-0

EC Name:

1,2,4-trichlorobenzene

Cas Number:

120-82-1

Molecular formula:

C6H3Cl3

IUPAC Name:

1,2,4-trichlorobenzene

Details on test material:

-Name of test material (as cited in study report): 1,2,4-trichlorobenzene
-Analytical purity: no data

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Acclimation period: 2 weeks

Administration / exposure

Type of coverage:

other: see any other information on materials and methods incl. tables

Vehicle:

other: petroleum ether

Details on exposure:

TEST SITE
- Area of exposure: inner surface of one ear


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): test solutions were applied at the rate of 0.2 mL per exposure.


VEHICLE
- Amount(s) applied (volume or weight with unit): solvent was applied at the rate of 0.2 mL per exposure


POSITIVE CONTROL:
Amount(s) applied (volume or weight with unit): Hexachlorodiphenyloxide was applied as a 10% emulsion in olive oil

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

3 times per week

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 25 or 100 % test substance solution per application
Basis:
no data

No. of animals per sex per dose:

see any other information on materials and methods incl. tables

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

other: positive control

Positive control:

hexachlorodiphenyloxide

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Gross pathology

At necropsy, performed on all animals, all positive control rabbits showed gross hepatic changes: the livers appeared rough, granular, tough, yellowish-brown in color and in two rabbits, margins were much thickened and yellowish-areas were noted throughout the organ. The negative control, solvent control, and test animals did not show meaningful visceral changes at necropsy.

 

Microscopic pathology

 

With the regard to the effect on the skin see Endpoint 7.3.1, key, 2, Powers, rabbit, IUC4.

Sections of liver, kidney, spleen and bone marrow from hexachlorodiphenyloxide-exposed rabbits revealed hepatic damage in all animals characterized by focal hepatocyte hypertrophy, focal necrosis, fibrosis and bile stasis, toxic tubular degeneration of the kidney on one rabbit, lymphoid atrophy of the spleen in one animal, and hypocellularity (hypoplasia) of the bone marrow in all animals. Visceral lesions in the remaining animals were not remarkable and were consistent with spontaneous disease.