1-chloro-4-nitrobenzene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

No information

Author:

Chou BJ, Leach CL, Miller RA, Horstman MG, Ragan HA, Bucher JR, Roycroft JH (1991) 13-week subchronic inhalation|toxicity of 4-chloronitrobenzene (4-DCB) in rodents. The Toxicologist 11: 87 Abstr. 262

Reference 2

Reference Type:

publication

Title:

No information

Author:

NTP (1993) 2-Chloronitrobenene and 4-Chloronitrobenzene: Administered by inhalation to F344/N rats and B6C3F1 mice. Toxicity Report Series No. 33, NIH Publication, 93-3382, July/1993

Reference 3

Reference Type:

publication

Title:

No information

Author:

Travlos GS, Mahler J, Ragan HA, Chou BJ, Bucher JR (1996) Thirteen-Week Inhalation Toxicity of 2- and 4-Chloronitrobenzene in F344/N Rats and B6C3F1 Mice. Fundam Appl Toxicol 30: 75-92

Materials and methods

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): 1-chloro-4-nitrobenzene
- Analytical purity: approx. 99 %

Test animals

Species:

rat

Strain:

other: F344/N

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Duration of treatment / exposure:

13 w

Frequency of treatment:

6 h/d, 5 d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1.5, 3, 6, 12 or 24 ppm (= ca. 0.0, 9.81, 19.62, 39.24, 78.48 or 156.96 mg/m³ air)
Basis:

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Post-exposure period: no

Examinations

Statistics:

Parametric multiple comparisons procedures of Williams or Dunnett, nonparametric multiple comparisons methods of Shirley or Dunn, Jonckheere's test or trend-sensitive test, outlier test of Dixon and Massey

Results and discussion

Effect levels

Dose descriptor:

LOAEC

Effect level:

ca. 9.81 mg/m³ air

Sex:

male/female

Basis for effect level:

other: haematology (MetHb formation, Heinz bodies)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

no clear clinical signs of toxicity,
no rat died, 3 ppm-gr.: 1 female killed moribund due to
malocclusion,
mean body weight gain similar to those of the respective
controls. 
haematology, male(m) and female(f):
concentration-related increase in methaemoglobinaemia (m:
significant (sign.) from 1.5 ppm at day(d)3 at all time
points with max. of 4.13 g/dl at d3 in 24 ppm-gr; f: sign.
from 1.5 ppm at d3 at all time points with max. of 5.90 g/dl
at d3 in 24 ppm-gr), reticulocyte count (m: sign. d3: 1.5
and 24 ppm, d23 >= 6 ppm, week(w)13 >= 1.5 ppm; f: sign. d3
24 ppm, d23 >= 3 ppm, w13 >= 3 ppm), nucleated erythrocytes
and leucocyte count (predominantly at the highest dose
groups in males and females);
concentration-related decrease in haematocrit, haemoglobin
and RBC at all time points; concentration and time-dependent
alterations of  RBC morphology, severity decreased with
decreasing concentration. RBC indices (MCV, MCH, MCHC) were
increased in males and females exposed to 12 ppm and above
at d23  and exposed to 6 ppm and above at w13. MCV and MCHc
were increased  in females exposed to 1.5 ppm and above at
w13, MCHC in males and females exposed to 24 ppm at d3
clinical chemistry, males and females:
Changes in alanine aminotransferase (decrease), sorbitol
dehydrogenase (increase) and alkaline phospatase activities
(decrease)
bile acid levels increase (m: >=3 ppm, all almost every time
points, f:>=6 ppm d3, d23 >=12 ppm). Increase in serum
activities of sorbitol dehydrogenase in various exposure
groups at different time points
pathology:
increase in abs. and rel. spleen weight (m >=3 ppm, f >=6
ppm), liver weight (m: 24 ppm, f >=6 ppm), kidney (m and f:
24 ppm), decrease in abs. and rel. testes weight (24 ppm); 
incidence of enlarged and darkened spleens in male and
female rats increased with increasing concentrations; 12, 24
ppm: kidneys darkened (female only), mediastinal lymph nodes
enlarged (males and females)
histopathology:
Increasing in severity (average severity is based on the
number of animals with lesions: 1=minimal, 2=mild,
3=moderate, 4=marked) and incidences with increasing
concentration (contr., low to high dose): bone marrow:
haematopoietic cell proliferation (m: = 0/10,
0/3/10/10/10(2.8), f: 0/10, 0/9/10/10/10(3.8)) hadrian
gland: chronic inflammation (m: 2(1), 1/1/3/1/8(2.2), f:
1/10(1.0), 2/4/5/8/10(3.0)), kidney: hyaline droplet
nephropathy (m: 0/10, 8/9/10/10/10(3.0)) and tubule pigment
(m: 0/10, 0/0/0/8/10(1.0), f: 0/10, 0/0/10/10/10(3.0))
liver: haemosiderin (m: 0/10, 0/0/0/9/10(1.0), f: 0/10,
0/7/10/10/10(2.4)), mediastinal lymph nodes: histiocytic
hyperplasia (m: 0/10, 0/0/0/4/9(2.3), f: 0/10,
0/0/0/6/10(2.7)), spleen: congestion (m:0,
10/10/10/10/10(3.0), f: 0/10, 10/10/10/10/10(3.0)),
haemosiderin (m:0/10, 10/10/10/10/10(1.0), f: 3/10(1.0),
10/9/10/10/10(1.0)) haematopoietic cell proliferation m:
0/10,0/10/9/10/10(1.0)), f: 0/10, 0/9/10/9/10(2.0)) capsular
fibrosis (m: 0/10, 0/4/8/10/10(2.1), f: 0/10,
0/2/10/10/10(2.3)), testis atrophy (m: 1/10(4.0),
2/1/0/1/10(1.6))