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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Specific investigations: other studies

Currently viewing:

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

Constituent 1
Chemical structure
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.