Registration Dossier

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
repeated dose 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

Referenceopen allclose all

Title:
No information
Author:
Horstman, M.G. et al.: The Toxicologist 11, 87 (1991) |(abstr.)
Title:
No information
Author:
NTP, Technical Report Series No. 33, NIH Publication|93-3382, July/1993
Title:
No information
Author:
Travlos G.S. et al., Fundam. Appl. Toxicol. 30, 75-92 (1996)

Materials and methods

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-chloro-2-nitrobenzene
- Analytical purity: 99 %

Test animals

Species:
rat
Strain:
other: F344/N
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Duration of treatment / exposure:
13 w
Frequency of treatment:
6 h/d, 5 d/w
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1.1, 2.3, 4.5, 9 or 18 ppm (approx. 0, 7, 14.7, 28.8, 57.6, 115.2 mg/m³)
Basis:

Control animals:
yes
Details on study design:
Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:
LOAEC
Effect level:
ca. 1.1 ppm
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

clinical signs:
no clear signs of toxicity (no other information), 
no deaths, no differences in body weight gain or terminal
body weight compared to controls;
haematology, male and female: 
concentration-related increase in methaemoglobinaemia (m
sign: from 1.1 ppm at d23; from 2.3 ppm at all time points
with max of 1.14 g/dl at 18 ppm; f sign.: from 1.1 ppm at
week 13 and from 2.3 ppm at all time points with max of 1.04
g/dl at 18 ppm), reticulocyte count (sign. at all dose
groups at week 13), nucleated erythrocytes, leucocyte count
(predominantly at the highest dose groups of male and
females);   concentration-related decrease in haematocrit,
haemoglobin, RBC (m. sign.: 1.1 ppm(d23), 4.4 ppm
(week13), 9 ppm (d4,week13),18 ppm (at all time points); f.
sign.: at every dose group at week13), MCH and MCHC (only in
females)
clinical chemistry, male and female:
increase in serum activities of sorbitol dehydrogenase and
alanine aminotransferase in different male and female
exposure groups at various time points, decrease in alkaline
phosphatase 
pathology: dark spleen (1 female, 2 males, 18 ppm) 
concentration-related increases in liver, spleen and right
kidney weight
Histopathologic changes:
liver: basophilia of centrilobular hepatocytes, kidney:
pigmentation and regeneration of the proximal convoluted
tubules, spleenic congestion was observed in all exposed and
control rats: in males with dose-dependent increase in
severity and in females with dose-dependent increase in
incidences; nose: hyperplasia of the nasal cavity
respiratory epithelium

Applicant's summary and conclusion