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Toxicological information

Specific investigations: other studies

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.