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Diss Factsheets

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Stearic anhydride
EC Number:
211-318-6
EC Name:
Stearic anhydride
Cas Number:
638-08-4
Molecular formula:
C36H70O3
IUPAC Name:
octadecanoic anhydride

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentrations of the test item in the exposure chamber were analyzed by collecting samples at 2,
4 and 6 hours after chamber equilibrium time during the exposure period. Samples in triplicate were taken for each time point for dose concentration analysis. The chamber concentration analysis was performed once a week (on days 1, 8, 15, 22).
Duration of treatment / exposure:
up to 28 days (4 Weeks)
Frequency of treatment:
6 hours exposure daily, 5 days a week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/L air
Remarks:
Control group
Dose / conc.:
0.6 mg/L air (nominal)
Dose / conc.:
1.2 mg/L air
Dose / conc.:
2.4 mg/L air
Remarks:
including recovery group
No. of animals per sex per dose:
5 males, 5 females for each group
Control animals:
yes, concurrent no treatment

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs of illness were observed in any of the male and female animals of main study treated concentration of 0.60, 1.20 and 2.40 mg/L.
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in any of the male and female animals of main study treated with test item concentration of 0.60, 1.20 and 2.40 mg/L throughout the experimental period.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No adverse effect on body weight and body weight gain (%) was observed for treated groups when
compared with vehicle control group. The changes observed were within the historical background
range with respect to age and sex of the animals.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No adverse effects on food consumption were observed in treated group animals when compared with control group animals.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Hematology parameters viz Erythrocyte count (RBC), Hemoglobin (Hb), Hematocrit (PCV), Mean
corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), White blood cell count (WBC), Differential Counts (Neutrophils, basophils and Lymphocytes), Reticulocyte, platelets, APTT and Prothrombin time (PT) did not show any
toxicologically relevant findings in both the sexes of treatment group and females of recovery group.
At week 6, reticulocyte count and basophils were found to be increased in high dose (G4R) when compared with control (G1R) in males.
The significant changes observed in the hematological parameters are marginal and could not be
attributed to the test item administration as these values were within clinical and biological variation.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Clinical biochemistry parameters viz Blood Urea Nitrogen, Creatinine, Cholesterol, Triglycerides,
Alkaline phosphatase (ALP), Bilirubin total, Sodium (Na), Chloride (CO, Calcium (Ca), Protein,
Albumin, Globulin and A/G Ratio did not show any toxicologically relevant findings in males of
treatment group. There is no toxicologically relevant findings except glucose (GLU) in males of
recovery group. There is no toxicologically relevant findings in females of recovery group
Week 4 analyses showed statistically increased glucose (GLU) levels in intermediate dose group (G3) and high dose group (G4) when compared with control group (G1) for males. Increased Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in intermediate dose group (G3) whereas increased Phosphorus (PHOS) and Potassium (K) levels in high dose group (G4) when compared with control group (G1) for males. In females, decreased glucose (GLU) and Increased Phosphorus (PHOS) levels were observed in intermediate dose group (G3) and high dose group (G4) when compared with control group (01). Increased Calcium (Ca) levels in low dose group (G2) and high dose group (G4) in females) when compared with control group (G1). Increased Globulin (GLB) levels in intermediate dose group (G3) when compared with control group (G1).
Even though there is statistical significance observed, these changes may not be biologically significant since all the values were well within the normal biological range.
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related changes in terminal fasting body weight and organ weights in any of
the treatment groups when compared to vehicle control.
In main group males, there was increase in absolute and relative weight of liver in group 3 when
compared to control. In recovery group male animals, increase in absolute and relative weight of
adrenal and decrease in absolute and relative weight of thymus was observed in group 4R when compared to the corresponding control group. These changes were considered incidental in the absence of similar weight changes in the main group high dose (Group 4) animals.
In females, increase in absolute weight of brain in group 3 and 4 when compared to control group was
considered incidental as there was no changes in the relative organ weights for these organs. In recovery group female animals, decrease in absolute and relative weight of spleen was observed in
group 4R when compared to the corresponding control group. These changes were considered
incidental as there were no weight changes observed at main group high dose animals when compared to control.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related gross findings in males and females.
Single incidence of unilateral small sized testes was observed in group 1 male animal (Animal No.
04). Microscopically, atrophy of seminiferous tubules in testes of moderate severity was observed and
was considered incidental. In animal No. 28 of group 3, dark red discoloration in liver, enlarged spleen and dilated heart was observed. Microscopically, congestion with moderate and minimal severity was observed in liver and spleen respectively and heart showed moderately dilated right auricle and ventricle. Congestion in liver and spleen may be attributed to right sided heart failure.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
There were no treatment related histopathological findings attributable to the test item in any tissues of
high dose (2.40 mg/L) group animals of both sexes.
One or two incidence of microscopic findings observed in liver, lungs, testes, epididymides and larynx were considered incidental as they were common background findings observed in the species.
Histopathological findings: neoplastic:
no effects observed

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
>= 2.4 mg/L air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no treatment-related effects were observed

Target system / organ toxicity

Key result
Critical effects observed:
no
Lowest effective dose / conc.:
2.4 mg/L air (nominal)
System:
other: no treatment-related effects were observed

Applicant's summary and conclusion

Conclusions:
Stearinsaureanhydrid was exposed daily to group of Wistar rats for a period of 22 days at doses of 0.6, 1.2 and 2.4 mg/L. No test item related changes in the body weights, feed consumption, haematology and organ weights were observed. Macroscopic and microscopic examination revealed no abnormality attributable to the treatment at the highest dose (2.4 mg/L). In the absence of gross and histopathological findings in the organs and due to negligible change in the profile of animals of high dose (G4) high dose is considered to have low observed effect. Hence, under the conditions of the experiment and based on the findings of the present study entitled "Acute Inhalation Toxicity Study in Rats with Stearinsaureanhydrid", the No Observed Adverse Effect Concentration (NOAEC) was found to be the highest dose level employed, i.e. 2.40 mg/L.