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Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 weeks
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Petroleum hydrocarbon toxicity studies. III. Animal and human response to vapors of Stoddard solvent.
Author:
Carpenter CP, Kinkead ER, Geary Jr, Sullivan LJ, & King JM
Year:
1975
Bibliographic source:
Toxicol Appl Pharmacol, 32: 282-297.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Principles of method if other than guideline:
25 male Harlan-Wistar rats to white spirit (Stoddard solvent) vapour at levels of 0 mg/m3, 480 mg/m3 (84 ppm), 1100 mg/m3 (190 ppm) and 1900 mg/m3 (330 ppm) (boiling range, 152-194°C; 47.7% aliphatics, 37.6% cyclic aliphatics, 14.7% aromatics) for a period of 13 weeks(6 h/day, 5 days/week).
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Stoddard solvent
EC Number:
232-489-3
EC Name:
Stoddard solvent
Cas Number:
8052-41-3
Molecular formula:
C10H22
IUPAC Name:
stoddard solvent
Test material form:
liquid
Specific details on test material used for the study:
Stoddard solvent;boiling range, 152-194°C; 47.7% aliphatics, 37.6% cyclic aliphatics, 14.7% aromatics

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
25 male Harlan-Wistar rats
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Harlan-Wistar rats
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 8-9 weeks
- Weight at study initiation (mean): 211-213 g;
- Housing: 5 per cage
- Acclimation period: 26 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks on MMAD:
no data
Details on inhalation exposure:
25 male Harlan-Wistar rats to white spirit (Stoddard solvent) vapour at levels of 0 mg/m3, 480 mg/m3 (84 ppm), 1100 mg/m3 (190 ppm) and 1900 mg/m3 (330 ppm) (boiling range, 152-194°C; 47.7% aliphatics, 37.6% cyclic aliphatics, 14.7% aromatics) for a period of 13 weeks(6 h/day, 5 days/week).
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Nominal concentrations were determined daily, and calculations of concentration in ppm were made by using weight loss data and assuming an average molecular weight of 142 g/mol for the Stoddard solvent. Analytical concentrations were determined by drawing samples from the chambers into a gas chromatograph equipped with a flame ionization detector.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 h/day, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air
Dose / conc.:
480 mg/m³ air
Remarks:
84 ppm=480 mg/m3
Dose / conc.:
1 100 mg/m³ air
Remarks:
190 ppm=1100 mg/m3
Dose / conc.:
1 900 mg/m³ air
Remarks:
330 ppm=1900 mg/m3
No. of animals per sex per dose:
25 male Harlan-Wistar rats
Control animals:
yes
Details on study design:
25 male Harlan-Wistar rats to white spirit (Stoddard solvent) vapour at levels of 0 mg/m3, 480 mg/m3 (84 ppm), 1100 mg/m3 (190 ppm) and 1900 mg/m3 (330 ppm) (boiling range, 152-194°C; 47.7% aliphatics, 37.6% cyclic aliphatics, 14.7% aromatics) for a period of 13 weeks(6 h/day, 5 days/week).

Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes, all animals
- Time schedule: twice daily

BODY WEIGHT: Yes, all animals
- Time schedule for examinations: weighed initially and 1 x week thereafter

CLINICAL PATHOLOGY: Yes
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Histopathological lesions of the kidneys and dilated tubules were found in 6 out of 9 and 3 out of 9 rats exposed to 1900 and 1100 mg/m3, respectively
Mortality:
no mortality observed
Description (incidence):
No treatment-related deaths were observed.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No differences were found in weight gain.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No differences were found in weight gain.
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
Histopathological lesions of the kidneys and dilated tubules were found in 6 out of 9 and 3 out of 9 rats exposed to 1900 and 1100 mg/m3, respectively.
These lesions were also noted in rats killed after only 8 weeks of exposure.
Significant, although not dose-related, changes in haematological values were thought to be mainly a consequence of the deviant values found in the control group. No differences were found in weight gain.


Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
1 100 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
Remarks on result:
other:
Remarks:
Based on histopathological lesions of the kidneys and dilated tubules found in 3 out of 9 rats exposed to 1100 mg/m3,
Dose descriptor:
LOAEC
Effect level:
1 900 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
organ weights and organ / body weight ratios
Remarks on result:
other:
Remarks:
Based on histopathological lesions of the kidneys and dilated tubules found in 6 out of 9 rats exposed to 1900 mg/m3,

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Based on histopathological lesions of the kidneys and dilated tubules found in 3 out of 9 rats exposed to 1100 mg/m3,

The no-observed-adverse-effect concentration (NOAEC) was considered to be 1100 mg/m³.

Applicant's summary and conclusion

Conclusions:
Sub-chronic exposure to male rats for of 13 weeks(6 h/day, 5 days/week) periods produced no significant finding.
The only significant finding was slight to moderate tubular regeneration in male rats which is consistent with alpha-2u-globulin induced nephropathy.
The no-observed-adverse-effect concentration (NOAEC) was considered to be 1100 mg/m³.
Executive summary:

Based on the results of this study, repeated inhalation exposure of male rats to Stoddard solvent at mean analytical concentrations of 1100 mg/m³ (190 ppm) and 1900 mg/m³ (330 ppm) was well-tolerated with no adverse effects .

The no-observed-adverse-effect concentration (NOAEC) was considered to be 1100 mg/m³.