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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Only male rats tested, organ weights not determined, no recovery period.

Data source

Reference
Reference Type:
publication
Title:
Petroleum hydrocarbon toxicity studies XVII. Animal response to n-nonane vapor
Author:
Carpenter, C.P. et al.
Year:
1978
Bibliographic source:
Toxicology and Applied Pharmacology 44: 53-61

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
Only males tested, no recovery period, organ weights not determined
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nonane
EC Number:
203-913-4
EC Name:
Nonane
Cas Number:
111-84-2
Molecular formula:
C9H20
IUPAC Name:
nonane
Constituent 2
Reference substance name:
203-193-4
IUPAC Name:
203-193-4
Details on test material:
- Name of test material (as cited in study report): n-Nonane
- Analytical purity: technical grade n-nonane, 98.4 %

Test animals

Species:
rat
Strain:
other: Harlan-Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 216.1 ± 35.7 - 227.8 ± 37.7 g (mean values)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: not applicable, vapour
Details on inhalation exposure:
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber air samples, collected with airtight syringes, were injected within 30 seconds after capture into a gas chromatograph, samples were taken twice a day. Actual doses received: 1.9, 3.1, 8.4 mg/L (nominal exposure levels: 2.5, 5.0, 10 mg/L).
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
1.9, 3.1, 8.4 mg/L (corresponding to 360, 590, 1600 ppm)
Basis:
analytical conc.
No. of animals per sex per dose:
25 males
Control animals:
yes, sham-exposed
Details on study design:
- Post-exposure recovery period in satellite groups: no
Positive control:
not applicable

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: overall appearance, behaviour


DETAILED CLINICAL OBSERVATIONS: Yes: 3, 3, and 8-9 rats/group, respectively
- Time schedule: at 3, 8 and 13 weeks of exposure (19, 38 and 63 days actual exposure, respectively): prior to sacrifice

BODY WEIGHT: Yes
- Time schedule for examinations: weekly


HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 3, 8 and 13 weeks of exposure (19, 38 and 63 days actual exposure, respectively): prior to sacrifice
- Anaesthetic used for blood collection: No (tail vein)
- How many animals: 3, 3, and 8-9 rats/group, respectively (sacrificed)
- Parameters examined: hematocrit, total erythrocyte counts, reticulocyte counts, total and differential leukocyte counts


CLINICAL CHEMISTRY: Yes (from severed cervical vessels)
- Time schedule for collection of blood: at 3, 8 and 13 weeks of exposure (19, 38 and 63 days actual exposure, respectively)
- How many animals: 3, 3, and 8-9 rats/group, respectively (sacrificed)
- Parameters examined: serum alklaline phosphatase, SGOT, SGPT, blood urea nitrogen


URINALYSIS: Yes
- Time schedule for collection of urine: at 3, 8 and 13 weeks of exposure (19, 38 and 63 days actual exposure, respectively): prior to sacrifice
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, but organ weights not determined.
HISTOPATHOLOGY: Yes: brain, respiratory tract, heart, thyroid, liver, kidney, adrenal, spleen, pancreas, stomach and intestine, skeletal muscle, bone marrow and peripheral nerve. Reproductive organs were not examined
Statistics:
Results of quantitative continuous variables (e.g. body weight changes) were evaluated using Bartlett's homogeneity of variance, analysis of variance and rank sum. Duncan's multiple range test was used if F for ANOVA was significantly high. If Bartlett's test indicated heterogeneous variances, the F-test was used for each group vs controls. If these F-tests were not significant, Student's t-test was used; if significant, means were compared by Cochran's t-test or rank sum test. Frequency data (e.g. mortality, micropathological conditions) were compared between groups by Chi square with Yates correction for continuity. Critical level of significance was 0.05.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
1.9 mg/L: 2 animals died during the 13 week exposure period, one during the 46th exposure and the other after the 52nd exposure. These deaths were determined to be not dose or treatment related.
3.1 mg/L: All animals survived through study termination. There were no signs of distress throughout the 13-week study. 
8.4 mg/L: Two rats died during the first day of exposure.

BODY WEIGHT AND WEIGHT GAIN
1.9 mg/L: Both deceased animals showed weight gains during the week before they died. 
3.1 mg/L: No effects reported.
8.4 mg/L: The mean body weights or mean body weight changes of rats were statistically significantly lower than controls when compared at 3, 17, 32, 46 and 61 exposure days.


HAEMATOLOGY
No effects reported.


CLINICAL CHEMISTRY
8.4 mg/L: Serum glutamic pyruvic transaminase value for blood taken from rats after 4 weeks was statistically significantly greater than that of controls. However, the increases were not observed after 8 or 13 weeks suggesting a transient effect. 
Other dose groups: No effects reported.


URINALYSIS
No effects reported.


GROSS PATHOLOGY
1.9 mg/L: Gross and micropathological examination of the lung tissue of both deceased animals revealed suppurative bronchopneumonia. These deaths were determined to be not dose or treatment related.
3.1 mg/L: No effects reported.
8.4 mg/L: Two rats died during the first day of exposure. Lung congestion and hemorrhage were noted at necropsy and no other significant lesions were found upon histopathological examination.

 
HISTOPATHOLOGY: NON-NEOPLASTIC
8.4 mg/L: Micropathological evaluation of tissues after 4, 8, and 13 weeks revealed only common sporadic lesions that were not considered to be treatment related.
Other dose groups: No effects reported.

Effect levels

Dose descriptor:
NOAEC
Effect level:
8 400 mg/m³ air (analytical)
Sex:
male
Basis for effect level:
other: clinical signs and body weight

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Under the conditions of this inhalation study in rats, the NOAEC was 8.4 mg/L.

Applicant's summary and conclusion

Conclusions:
Under the conditions of this inhalation study in rats, the NOAEC was 8.4 mg/L.
Executive summary:

Under the conditions of this inhalation study in rats, the NOAEC was 8.4 mg/L.