Registration Dossier

Toxicological information

Acute Toxicity: other routes

Currently viewing:

Administrative data

Endpoint:
acute toxicity: other routes
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

Data source

Reference
Reference Type:
publication
Title:
Acute effects of 3,4-dichloroaniline on blood of male wistar rats
Author:
Guilhermino, L et al.
Year:
1998
Bibliographic source:
chemosphere 37(4): 619-632

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Changes of biochemical and cellular blood parameters in male wistar rats after intraperitoneal injection of five different doses of 3,4-dichloroaniline.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,4-dichloroaniline
- Analytical purity: 98 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute Gulbenkian of science, Portugal
- Weight at study initiation: 120-190 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- °C
- Humidity (%): air-conditioned
- Air changes (per hr): air-conditioned
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: sesame oil
Doses:
0, 81, 162, 324, 486 and 568 mg / kg bw
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
examinations performed: body weight, organ weights (liver, kidneys, spleen, thymus), hematological and biochemical parameters (red blood cell counts, hemoglobin content, hematocrit, MCHC, platelets, leukocytes, methemoglobin, alanine transferase, urea, creatinine), histological examination of spleen tissue samples
Statistics:
ANOVA and Turkey test

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
other: LOEL
Effect level:
324 mg/kg bw
Remarks on result:
other: observed
Sex:
male
Dose descriptor:
other: ED50
Effect level:
224 mg/kg bw
Remarks on result:
other: calculated for methemoglobin formation
Mortality:
until 324 mg/ kg no deaths
486 mg/ kg group mortality: 1/8
568 mg/ kg group mortality: 3/8
Clinical signs:
no differences in blood cell parameters between non-treated and vehicle-treated rats;
differences among treatments statistically significant at doses higher than 324 mg/ kg;
dose-dependent increase in methemoglobin formation (ED50=224 mg/ kg bw);
decrease in blood platelet and leukocyte numbers;
giant platelets, red blood cell polychromasia;
reversal of lymphocyte/ neutrophil ratio due to deacrease of lymphocytes and increase of neutrophils;
no treatment related changes on red blood cells, hemoglobin, hematocrit and MCHC found;
increase in plasmatic urea and creatinine, no significant differences in ALT activity at all doses
Body weight:
no data
Gross pathology:
no data
Other findings:
- Organ weights: significant increase of "organ weight/ body weight ratio" for spleen, thymus and kidney
- Histopathology of the spleen: reduced hematopoiesis, megakaryocytes with dysplasia, hyperplasia of the white pulp, trabecular and vascular wall fibrosis and hyperaemia ad doses equal or higher than 324 mg/ kg even though no change in organ weight observed at 324 mg/kg dose
- Potential target organs: spleen and thymus

Applicant's summary and conclusion

Executive summary:

Guilhermino, L. et al. 1998

The aim of this study was the evaluation of the acute effects of 3,4-dichloroaniline injection (i.p.) in male Wistar rats on blood parameters.

Therefore groups of 8 male Wistar rats were injected 1 mL sesame oil with either 0, 81, 162, 324, 486 and 568 mg

3,4-dichloroaniline/ kg bw. The mortality within 24 h, blood parameters, relative organ weights and morphology were determinded. The observed LOEL was 324 mg/ kg bw. Higher doses caused hyperthrophy of spleen, thymus and kidney, as well as an increase of neutrophils and a reduction of leukocytes and lymphocytes. Furthermore the dose-dependent induction of methemoglobin formation indicated hematotoxicity. Histopathological changes of the blood were the formation of giant platelets and red blood cell polychromasia indicating accelerated trombopoiesis caused by spleenic lesions. Nephrotoxicity is indicated by the increase of urea and creatinine as well as the kidney-hypertrophy. Methemoglobin formation is the most sensitive parameter resulting from 3,4-dichloroaniline exposure.