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EC number: 203-481-7 | CAS number: 107-31-3
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2010
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- Acute and Subchronic Inhalation Toxicity Evaluation of
Methyl Formate in Rats - Author:
- Hyeon-Yeong Kim
- Year:
- 2 010
- Bibliographic source:
- ENVIRONMENTAL HEALTH & TOXICOLOGY, Vol. 25, No. 2, 13 1- 143 (20 10)
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (90-Day (Subchronic) Inhalation Toxicity Study
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Methyl formate
- EC Number:
- 203-481-7
- EC Name:
- Methyl formate
- Cas Number:
- 107-31-3
- Molecular formula:
- C₂H₄O₂
- IUPAC Name:
- methyl formate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- TEST ANIMALS:
-Source: SLC Japan - Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- not specified
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 5 days/week, 6 hours/day
Doses / concentrations
- Remarks:
- Doses/concentrations: 0, 100, 400, 1600 ppm (0, 0,25, 0,98, 3,92 mg/L)
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- BODY WEIGHT: YES
- Time schedule for examinations: recorded on a weekly base
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination in week 13
- Parameters checked in table No. B1 (report, Appendix B) were examined
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination in week 13
- Parameters checked in table No. B1 (report, Appendix B) were examined.
- Histopathology: Yes
Organs were weighted: brain, spleen, liver, thymus, kidney (right/left), lung (right/left), heart, adrenal grand (right/left), ovary (right/left)
Results and discussion
Results of examinations
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced terminal body weight after exposure to 400 ppm (0.98 mg/L) and 1600 ppm (3.92 mg/L).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced food intake after exposure to 400 ppm (0.98 mg/L) and 1600 ppm (3.92 mg/L).
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased level of neutrophils (male/female), monocytes (female), eosinophils (male) and decreased level of reticulocytes (male), lymphocytes (male/female) after exposure of 1600 ppm.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Serum values: decreased level in Calcium (male/female) and increased A/G ratio (male/female).
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased weights of left ovary and brain in female rats after exposure to 400 ppm. After exposure to 1600 ppm increased adrenal grand, kidney, heart, lung, brain in both sexes and increased thymus in female, increased testis in male rats.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Atrophy of nasal respiratory epithelium, degradation, regeneration and contraction of olfactory cells after exposure to 1600 ppm.
Effect levels
open allclose all
- Dose descriptor:
- LOAEC
- Remarks:
- systemic
- Effect level:
- 400 ppm
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- organ weights and organ / body weight ratios
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 100 ppm
- Basis for effect level:
- haematology
- Remarks on result:
- other: at the next higher dose level changes in body weight and organ weights were observed
- Dose descriptor:
- LOAEC
- Remarks:
- local
- Effect level:
- 1 600 ppm
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 400 ppm
- Basis for effect level:
- food consumption and compound intake
- haematology
- organ weights and organ / body weight ratios
- Remarks on result:
- other: at the next higher dose level nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells was observed
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 600 ppm
- System:
- respiratory system: upper respiratory tract
- Organ:
- lungs
- Treatment related:
- yes
Applicant's summary and conclusion
- Conclusions:
- Based on significantly decreased body and organ weights at 400 ppm a NOAEC of 100 ppm for systemic effects was derived. At 1600 ppm significantly decreased body and organ weights, non-neoplastic findings of repiratory epithelium and hematological findings were observed and a NOAEC of 400 ppm for local effects was derived.
- Executive summary:
In a 90-d repeated dose inhalation toxicity study Sprague-Dawley rats were exposed to methyl formate vapor at 0, 100, 400, 1600 ppm (0, 0,25, 0,98, 3,92 mg/L) 6 hours/day, 5 days/week for 13 weeks. No mortality was recorded throughout the study. A statistically significant reduced body weight development during the whole study period and reduced food consumption of male and female rats was observed after exposure to 400 and 1600 ppm compared to the control group. Reduction of body weight of 25% (male) and 20% (female) at the end of the study in the 1600 ppm group was observed. After exposure to 1600 ppm the organ weight of almost every examined organ was significantly increased (male/female) and hematologic and blood serum parameters indicate significant changes (reduced neutrophils and lymphocytes and increased albumin/globulin ratio) to the control group. At 1600 ppm atrophy of nasal respiratory epithelium, degeneration, regeneration and contraction of olfactory cells was found.
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