3,4-dichloroaniline

Specific investigations: other studies

Administrative data

Endpoint:

hematoxicity

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:

Role of metabolites in propanil-induced hemolytic anemia

Author:

McMillan, DC et al.

Year:

1991

Bibliographic source:

Toxicology and applied Pharmacology 110: 70-78

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

the hemolytic response was measured in vivo by assessing the capacity of the test material to reduce the survival of 51Cr-labeled erythrocytes

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

not applicable

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dichloroaniline

EC Number:

202-448-4

EC Name:

3,4-dichloroaniline

Cas Number:

95-76-1

Molecular formula:

C6H5Cl2N

IUPAC Name:

3,4-dichloroaniline

Details on test material:

- Name of test material: 3,4-dichloroaniline
- purity: recrystallized twice from hexane/chloroform (3/1, v/v)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Camm Research, Inc. (Wayne, NJ)
- Weight at study initiation: 130-150 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS

- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

maize oil

Details on exposure:

groups of 7 rats are exposed to different doses of test-material (0.8 to 1.8 mmol/kg)

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

i.p. injection preceeded by one (control) and followed by several blood samplings (75 µL) for 14 days from the orbital sinus (day 2, 4, 7,9,11,14)

Frequency of treatment:

single treatment

Post exposure period:

14 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0.8, 1.0, 1.5, 1.8 mmol/kg
Basis:
nominal conc.
concentration taken from figure, not mentioned in the methods

No. of animals per sex per dose:

7 male rats per dose

Examinations

Examinations:

see any other information on materials and methods

Results and discussion

Any other information on results incl. tables

The ED₅₀ of hemolysis after vivo exposure to 3,4 -DCA resembels that of Propanil = 1.8 mmol/ kg; the hemolytic potency of the N-hydroxy-3,4 -DCA metabolite is 10 -times greater (0.2 mmol/kg). In vitro exposure to 3,4 -DCA did not cause hemolysis, indicating metabolism of the test material. The 6 -hydroxy-metabolite did not cause removal of radioactivity from blood that was significantly different from controls (in vitro).

Applicant's summary and conclusion

Executive summary:

McMillan et al., (1991), Toxicology and applied Pharmacology 110: 70-78

The present studies were undertaken to determine the hemolytic potential of the propanil metabolite 3,4 dichloroaniline in hemotoxicity.

51Cr-labeled erythrocytes were readministered to male Sprague Dawley rats then groups of seven rats received 0.8 to 1.8 mmol 3,4-dichloroaniline/ kg body weight by i.p. administration of 3,4-dichloroaniline. The survival of the previously administered 51Cr-labeled erythrocytes was counted in a gamma-scintillation counter. The calculated ED₅₀ was about. 1.8 mmol/kg for 3,4 -dichloroaniline

When labeled erythrocytes were exposed in vitro to 3,4-dichloroaniline and then readministered to rats, no decrease in erythrocyte survival was observed, which indicated that the compound was not a direct-acting hemolytic agent . In contrast, erythrocyte survival was markedly reduced by ip administration or in vitro exposure to N-hydroxy-3,4-dichloroaniline (7.9.3 RL2, rat, hematotoxicity, in vitro, McMillan, DC, 1991).

These data indicate that N-hydroxy-3,4-dichloroaniline mediates 3,4 -dichloroaniline-induced hemolytic anemia, and that occupational exposure to 3,4 -dichloroaniline may result in an increased risk of hemolytic episodes.