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EC number: 203-721-0 | CAS number: 109-94-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Repeated dose oral
NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with test substance for 17 week by oral feed.
Repeated dose inhalation toxicity:
In a Repeated dose inhalation toxicity study, Sprague-Dawley male and female rats were inhaled with test substance in the concentration of 0, 0.2, 1 and 4 mg/L for 6 hr/day, 5 days by Whole body exposure for 90 days. Decrease in locomotor activity of the male and female rats were observed as compared to control, but recovered after the exposure ended at 4 mg/L. No mortality was observed during the study in treated rats as compared to control. Body weight gain significantly decreased in male and female rats from week 1 were observed as compared to control rats. Increased body weight gain on week 4 were observed in male rat as compared to control at 4 mg/L and increased body weight gain on week 4 in male rats were observed as compared to control at 1 mg/L. The increased body weight of the male rats exposed to 330 ppm at week 4 was not considered to be ethyl formate-related change because they were isolated changes. Significantly decreased in male and female rat were observed from week 1 and week 3, respectively as compared to control at 4 mg/L. Similarly, increased HGB and HCT level in male and decreased in Reti level n female rat were observed as compared to control and Ca and TG levels decreased in male and female rats respectively at 4 mg/L. Increase in Ketone body in male and female rat and Urobilinogen level in female rat were observed as compared to control. Increase in Ketone body in female rat were observed as compared to control at 1 mg/L. Reduced body weight and food consumption are occasionally accompanied by increase in urinary ketone levels, because energy metabolism under those conditions shifts from gluconeogenesis to incomplete oxidation of fatty acids. In addition, absolute and relative adrenal weight increased in male and female rats and relative brain, kidney, and lung in male and female rat as compared to control and Absolute or relative thymus weight or both decreased in male and female rats and absolute heart, kidney, liver, lung, and spleen weights decreased as compared to control at 4 mg/L. Degeneration, Squamous metaplasia and Lesions were mainly noted in the dorsal meatus and occasionally in the septum and turbinate in male and female rats as compared to control at 4 mg/L. Therefore, NOAEC was considered to 1 mg/L when Sprague-Dawley male and female rats were inhaled with ethyl formate for 90 days.
Repeated dose dermal toxicity:
10 weeks repeated dermal study was conducted on male “s” strain mice with the dose concentration of 2760 mg/kg bw/day (0.3ml in acetone applied) and the histopathologic analysis is done to determine the toxic effects. No significant activity was observed In terms of epidermal hyperplasia. Therefore, NOAEL was considered to be 2760 mg/kg bw/day when male “s” strain mice were treated for 10 weeks.
Key value for chemical safety assessment
- Toxic effect type:
- concentration-driven
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Data is from peer-reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: as below
- Principles of method if other than guideline:
- Subacute repeated toxicity study of test substance orally in rats
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Osborne-Mendel
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Housed individually in wire cages.
- Diet (e.g. ad libitum): food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period:No data available
ENVIRONMENTAL CONDITIONS
No data available - Route of administration:
- oral: feed
- Vehicle:
- other: Diet
- Details on oral exposure:
- Details on oral exposure
PREPARATION OF DOSING SOLUTIONS: Fresh diets were made by mixing test substance.
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Rat diet were used
- Concentration in vehicle: 0, 1000, 2500 and 10,000 ppm
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 17 weeks
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 other: mg/kg-bw/day
- Remarks:
- 0 ppm
- Dose / conc.:
- 50 other: mg/kg-bw/day
- Remarks:
- 1000 ppm
- Dose / conc.:
- 125 other: mg/kg-bw/day
- Remarks:
- 2500 ppm
- Dose / conc.:
- 500 other: mg/kg-bw/day
- Remarks:
- 10000 ppm
- No. of animals per sex per dose:
- Total: 80
0 ppm: 10 male and 10 female
50 ppm: 10 male and 10 female
125 ppm: 10 male and 10 female
500 ppm: 10 male and 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Details on study design
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Animals were randomized by weight (every level having animals of equal weight).
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available - Observations and examinations performed and frequency:
- Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included: Mortality was observed.
DETAILED CLINICAL OBSERVATIONS: Yes
–Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available.
FOOD EFFICIENCY:
No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination.
- Anaesthetic used for blood collection: No data available.
- Animals fasted: No data available.
- How many animals: No data available.
- Parameters checked in table [No.?] were examined: White cell counts, red cell counts, hemoglobin and haematocrits were examined.
CLINICAL CHEMISTRY: No data available
URINALYSIS: No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
OTHER:
Organ weight: Yes
Organs weighted:
Liver, kidneys, spleen, heart and testes were weighed. - Sacrifice and pathology:
- Sacrifice and pathology
GROSS PATHOLOGY: Yes, Necropsied with the process of exsanguinean.
Abnormalities, gross changes and the suspected reason for death were noted.
HISTOPATHOLOGY: Yes,
Organs were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.
A detailed microscopic examination in the study was done on 6 or 8 rats, evenly divided by sex, from the high dose group and the control group. If changes attributable to the test compound were found in the high dose group, additional animals on lower dosage levels were examined as indicated. So microscopic examination was not performed for 1000 and 2500 ppm dose level.
Organs examined: Liver, kidneys, spleen, heart, testes, and thoracic viscera, one hind leg, for bone, bone marrow and muscle were examined. - Other examinations:
- No data available
- Statistics:
- No data available
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effect were observed on growth of treated rat as compared to control.
- Mortality:
- no mortality observed
- Description (incidence):
- No effect on survival were observed in treated rat as compared to control.
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No effect were observed on hematological parameters of treated rat as compared to control.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross pathological abnormalities were observed in treated rat as compared to control.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No microscopic changes in the tissues were observed in treated rat as compared to control.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Pathological changes attributable to disease or age have not been included.
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- Conclusions:
- NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with tes substance for 17 week by oral feed.
- Executive summary:
In a Chronic repeated dose oral toxicity study, Osborne-Mendel male and female rats treated with test substance in the concentrations of50, 125 and 500mg/kg bw orally in diet. The animals were observed for clinical sign, body weight, food consumption, Hematology, gross and Histopathology. Results show that no effect was observed on survival and growth of all the treated rats. Similarly, no effect was observed on hematological parameters of treated rat as compared to control. In addition, No gross pathological abnormalities and microscopic changes in the tissues were observed in all treated rat as compared to control. Therefore, NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with test substance for 17 weeks by oral feed.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is Klimisch 2 and from publication
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from publication
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Principles of method if other than guideline:
- Repeated dose inhalation toxicity study of Ethyl Formate in Rats
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Japan SLC., Inc. (Hamamatsu, Japan) via Joongang Experimental Animal Co., Ltd. (Seoul, Korea)
- Age at study initiation: 7 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: Animals were housed individually in wire-bottomed stainless-steel mesh cages placed in exposure
Chambers.
- Diet (e.g. ad libitum): Commercial
rodent chow (PicoLab Rodent Diet 5053, LabDiet, USA) ad libitum, ad libitum
- Water (e.g. ad libitum): sterilized tap water, ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20%
- Air changes (per hr): 12-15 air changes/hr
- Photoperiod (hrs dark / hrs light): artificial lighting from 08:00 to 20:00 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole-body
exposure chambers (WITC-00-M, HCT Co., Korea)
- Method of holding animals in test chamber: Whole-body
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols: LVg-04-A
- Temperature, humidity, pressure in air chamber:23 °C
- Air flow rate:
- Air change rate:
- Method of particle size determination:
- Treatment of exhaust air:
TEST ATMOSPHERE
- Brief description of analytical method used: The ethyl formate levels were detected using gas chromatography (TRACE1310,
Thermo Scientific, China) with the following apparatus: detector, flame ionization detector; column, TraceGold TG- 5MS 5% diphenyl-95% dimethyl polysiloxane capillary column (30 m length, 0.25 mm i.d., 0.25 mm film thickness).
- Samples taken from breathing zone: yes
VEHICLE (if applicable)
- Justification for use and choice of vehicle: fresh air
- Composition of vehicle:
- Type and concentration of dispersant aid (if powder):
- Concentration of test material in vehicle: 0, 66, 330, and 1,320 ppm
- Lot/batch no. of vehicle (if required):
- Purity of vehicle: - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- using gas chromatography
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 6 hr/day, 5 days
- Dose / conc.:
- 0 mg/L air (analytical)
- Dose / conc.:
- 0.2 mg/L air (analytical)
- Dose / conc.:
- 1 mg/L air (analytical)
- Dose / conc.:
- 4 mg/L air (analytical)
- No. of animals per sex per dose:
- Total: 80
0 mg/L : 10 male, 10 female
0.2 mg/L : 10 male, 10 female
1 mg/L : 10 male, 10 female
4 mg/L : 10 male, 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Concentrations of 0, 0.2, 1 and 4 mg/L was selected based on a prior study and the OEL.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Before, during, and after the exposure period
- Cage side observations checked in table [No.?] were included.: Mortality were observed.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Before, during, and after the exposure period
BODY WEIGHT: Yes
- Time schedule for examinations: All the rats were weighed individually on the first exposure day and once a week after that.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: On week 12.
- Dose groups that were examined: All doses were examined.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: On day 90 of treatment.
- Anaesthetic used for blood collection: Yes, isoflurane
- Animals fasted: Yes, overnight
- How many animals: All 80 animals were examined.
- Parameters checked in table [No.?] were examined.: Prothrombin time (PT)
and activated partial thromboplastin time (APTT), total red blood cell (RBC) count, hemoglobin (HGB) concentration, hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), platelet (PLT) count, total white blood cell (WBC) count, differential WBC count (neutrophil, lymphocyte, monocyte, eosinophil, and basophil), reticulocyte (Reti) count, PT, and APTT were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On day 90 of treatment.
- Animals fasted: Yes, overnight
- How many animals: All 80 animals were examined.
- Parameters checked in table [No.?] were examined.: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen
(BUN), creatinine (Crea), total bilirubin (T-Bili), total protein (TP), albumin (Alb), A/G ratio, total cholesterol (TChol), triglyceride (TG), glucose (Glu), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphorus (P), and sodium (Na) were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: on week 13
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.: pH, protein, glucose, ketone body, bilirubin, occult blood, leukocyte, nitrite, urobilinogen, and specific gravity were examined.
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:
OTHER:
Organ weight:
Absolute and relative adrenals, brain, heart, kidneys, liver, spleen, testes, thymus, epididymides, lung, thyroids, ovaries, and uterus weight were examined. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
External body surfaces and all orifices were examined.
HISTOPATHOLOGY: Yes
Organ/tissues were preserved in 10% neutral buffered formalin:
Organ examined: adrenals, aorta, bone
marrow, brain, cecum, colon, duodenum, epididymides, esophagus, eyes, femur, Harderian glands, heart, ileum, jejunum, kidneys, larynx, liver, lung, lymph nodes (hilar and mesenteric), mammary gland, nasopharyngeal tissue, nerves (optic and sciatic), pancreas, parathyroids, pituitary, prostate, rectum, salivary glands (submandibular, sublingual,
and parotid), seminal vesicles, skeletal muscle, skin, spinal cord (cervical, lumbar, and thoracic), spleen, sternum, stifle joint, stomach, testes, teeth, thymus, thyroids, trachea, urinary bladder, ovaries, and uterus. The eyes/optic nerve and testes were preserved in Davidson’s solution
- Statistics:
- Statistical analysis was performed for body weight, food consumption, hematology and serum biochemistry parameters, organ weights, and organ/body weight. For the control and ethyl formate-exposed groups, the homogeneity of the variance of numerical data was determined using Levene’s test. Groups with homogenous and heterogeneous data were compared using one-way analysis of variance (ANOVA) and non-parametric Kruskal- Wallis test, respectively. If statistical significance was observed (p < 0.05), Dunnett’s test (for ANOVA) or the Steel test (for Kruskal-Wallis) was used for multiple comparisons of the control group with each dose group.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- when treated with 4 mg/L, decrease in locomotor activity of the male and female rats were observed as compared to control, but recovered after the exposure ended.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality were observed during the study in treated rats as compared to control.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, Body weight gain significantly decreased in male and female rats from week 1 were observed as compared to control rats. Increased body weight gain on week 4 were observed in male rat as compared to control.
When treated with 1 mg/L, increased body weight gain on week 4 in male rats were observed as compared to control.
The increased body weight of the male rats exposed to 330 ppm at week 4 was
not considered to be ethyl formate-related change because they were isolated changes. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, significantly decreased in male and female rat were observed from week 1 and week 3, respectively as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, increased HGB and HCT level in male and decreased in Reti level n female rat were observed as compared to control.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, Ca and TG levels decreased in male and female rats respectively.
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, incerase in Ketone body in male and femlae rat and Urobilinogen level in female rat were observed as compared to control.
When treated with 1 mg/L, incerase in Ketone body in femlae rat were observed as compared to control.
Reduced body weight and food consumption are occasionally accompanied by increase in urinary ketone levels, because energy metabolism under those conditions shifts from gluconeogenesis to incomplete oxidation of fatty acids. - Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, absolute and relative adrenal weight increased in male and female rats and relative brain, kidney, and lung in male and female rat as compered to control.
Absolute or relative thymus weight or both decreased in male and female rats and absolute heart, kidney, liver, lung, and spleen weights decreased as compered to control. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- All the macroscopic findings of the eye, liver, and ovaries were considered to be incidental and of no toxicological significance.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- When treated with 4 mg/L, Degeneration, Squamous metaplasia and Lesions were mainly noted in the dorsal meatus and occasionally in the septum and turbinate in male and female rats as compared to control.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEC
- Effect level:
- 1 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- organ weights and organ / body weight ratios
- urinalysis
- Remarks on result:
- other: No effect observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Conclusions:
- NOAEC was considered to 1 mg/L when Sprague-Dawley male and female rats were inhaled with test substance for 90 days.
- Executive summary:
In a Repeated dose inhalation toxicity study, Sprague-Dawley male and female rats were inhaled with test substance in the concentration of 0, 0.2, 1 and 4 mg/L for 6 hr/day, 5 days by Whole body exposure for 90 days. Decrease in locomotor activity of the male and female rats were observed as compared to control, but recovered after the exposure ended at 4 mg/L. No mortality was observed during the study in treated rats as compared to control. Body weight gain significantly decreased in male and female rats from week 1 were observed as compared to control rats. Increased body weight gain on week 4 were observed in male rat as compared to control at 4 mg/L and increased body weight gain on week 4 in male rats were observed as compared to control at 1 mg/L. The increased body weight of the male rats exposed to 330 ppm at week 4 was not considered to be ethyl formate-related change because they were isolated changes. Significantly decreased in male and female rat were observed from week 1 and week 3, respectively as compared to control at 4 mg/L. Similarly, increased HGB and HCT level in male and decreased in Reti level n female rat were observed as compared to control and Ca and TG levels decreased in male and female rats respectively at 4 mg/L. Increase in Ketone body in male and female rat and Urobilinogen level in female rat were observed as compared to control. Increase in Ketone body in female rat were observed as compared to control at 1 mg/L. Reduced body weight and food consumption are occasionally accompanied by increase in urinary ketone levels, because energy metabolism under those conditions shifts from gluconeogenesis to incomplete oxidation of fatty acids. In addition, absolute and relative adrenal weight increased in male and female rats and relative brain, kidney, and lung in male and female rat as compared to control and Absolute or relative thymus weight or both decreased in male and female rats and absolute heart, kidney, liver, lung, and spleen weights decreased as compared to control at 4 mg/L. Degeneration, Squamous metaplasia and Lesions were mainly noted in the dorsal meatus and occasionally in the septum and turbinate in male and female rats as compared to control at 4 mg/L. Therefore, NOAEC was considered to 1 mg/L when Sprague-Dawley male and female rats were inhaled with test substance for 90 days.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 1 000 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The data is K2 level and from publication
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer-reviewed journal
- Justification for type of information:
- Data is from peer-reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: as below mentioned
- Principles of method if other than guideline:
- Subchronic repeated dermal toxicity study was conducted to determine the toxicity of test substance in male mice.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: Stock albino of the " S " strain
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Details on test animal
- Age at study initiation: 7-9 weeks old.
- Diet :fed on cubes prepared according to the Rowett Institute plus fresh greenstuff twice a week formula
- Water : ad libitum
- Acclimation period: - Type of coverage:
- not specified
- Vehicle:
- other: Acetone
- Details on exposure:
- Details on dermal exposure
PREPARATION OF DOSING SOLUTIONS:
All solutions were prepared weight per total volume in the solvent. The preparation of glycine ethyl ester from the hydrochloride is described in the experimental section. The podophyllin extract used was prepared from the crude resin by extraction with acetone. Dosage was calculated on the dry weight of the extract after filtration and evaporation.
positive control: croton oil
TEST SITE
- Area of exposure: whole back, from forelimbs to tail.
The hair was clipped from the whole back, from forelimbs to tail, before treatment and at intervals when necessary. Solutions were delivered from calibrated pipettes, care being taken that they spread as evenly as possible over the whole
clipped area. A glass spreader was used for solutions which did not otherwise spread easily. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10 weeks
- Frequency of treatment:
- 10 weekly applications of 0.3ml neat agent
- Dose / conc.:
- 2 760 mg/kg bw/day
- No. of animals per sex per dose:
- No data
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- HISTOPATHOLOGY: Yes
- Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- not specified
- Dermal irritation:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Specimens of skin from mice additional to each group were removed under ether anaesthesia three days after one and/or two applications of the test substance. Mice which died during or were killed at the end of the tests were examined post mortem for lung adenomata and other abnormalities. Specimens for histological examination were fixed in Zenker's fluid, embedded in paraffin wax, and stained with haematoxylin and eosin-Biebrich scarlet.
- Histopathological findings: neoplastic:
- not specified
- Dose descriptor:
- NOEL
- Effect level:
- 2 760 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- histopathology: non-neoplastic
- Remarks on result:
- other: No Epidermal hyperplasia observed.
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Conclusions:
- NOAEL was considered to be 2760 mg/kg bw/day when male “s” strain mice were treated by test substance for 10 weeks dermally.
- Executive summary:
10 weeks repeated dermal study was conducted for test substance on male “s” strain mice with the dose concentration of 2760 mg/kg bw/day (0.3ml in acetone applied) and the histopathologic analysis is done to determine the toxic effects. No significant activity was observed In terms of epidermal hyperplasia. Therefore, NOAEL was considered to be 2760 mg/kg bw/day for test substance when male “s” strain mice were treated for 10 weeks
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 2 760 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- mouse
- Quality of whole database:
- Data is from peer-reviewed journal
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose oral toxicity:
Data available for the test chemicals was reviewed to determine the repeated dose oral toxicity of the test chemical Ethyl formate (109-94-4). The studies are as mentioned below:
In a Chronic repeated dose oral toxicity study, Osborne-Mendel male and female rats treated with test substance in the concentrations of50, 125 and 500mg/kg bw orally in diet. The animals were observed for clinical sign, body weight, food consumption, Hematology, gross and Histopathology. Results show that no effect was observed on survival and growth of all the treated rats. Similarly, no effect was observed on hematological parameters of treated rat as compared to control. In addition, No gross pathological abnormalities and microscopic changes in the tissues were observed in all treated rat as compared to control. Therefore, NOAEL was considered to be 500 mg/kg body weight/day when Osborne-Mendel male and female rats treated with test substance for 17 weeks by oral feed.
Based on the data available from the test chemical, Ethyl formate does not exhibit repeated dose oral toxicity. Hence the test chemical is not likely to classify as a repeated dose oral toxicity as per the criteria mentioned in CLP regulation.
Repeated dose inhalation toxicity:
Data available for the test chemicals was reviewed to determine the repeated dose oral toxicity of the test chemical and read across. The studies are as mentioned below:
In a Repeated dose inhalation toxicity study, Sprague-Dawley male and female rats were inhaled with test substance in the concentration of 0, 0.2, 1 and 4 mg/L for 6 hr/day, 5 days by Whole body exposure for 90 days. Decrease in locomotor activity of the male and female rats were observed as compared to control, but recovered after the exposure ended at 4 mg/L. No mortality was observed during the study in treated rats as compared to control. Body weight gain significantly decreased in male and female rats from week 1 were observed as compared to control rats. Increased body weight gain on week 4 were observed in male rat as compared to control at 4 mg/L and increased body weight gain on week 4 in male rats were observed as compared to control at 1 mg/L. The increased body weight of the male rats exposed to 330 ppm at week 4 was not considered to be ethyl formate-related change because they were isolated changes. Significantly decreased in male and female rat were observed from week 1 and week 3, respectively as compared to control at 4 mg/L. Similarly, increased HGB and HCT level in male and decreased in Reti level n female rat were observed as compared to control and Ca and TG levels decreased in male and female rats respectively at 4 mg/L. Increase in Ketone body in male and female rat and Urobilinogen level in female rat were observed as compared to control. Increase in Ketone body in female rat were observed as compared to control at 1 mg/L. Reduced body weight and food consumption are occasionally accompanied by increase in urinary ketone levels, because energy metabolism under those conditions shifts from gluconeogenesis to incomplete oxidation of fatty acids. In addition, absolute and relative adrenal weight increased in male and female rats and relative brain, kidney, and lung in male and female rat as compared to control and Absolute or relative thymus weight or both decreased in male and female rats and absolute heart, kidney, liver, lung, and spleen weights decreased as compared to control at 4 mg/L. Degeneration, Squamous metaplasia and Lesions were mainly noted in the dorsal meatus and occasionally in the septum and turbinate in male and female rats as compared to control at 4 mg/L. Therefore, NOAEC was considered to 1 mg/L when Sprague-Dawley male and female rats were inhaled with ethyl formate for 90 days.
Mainstream smoke from blended research cigarettes with (test) and without (control) the addition of ingredients to the tobacco was assayed for inhalation toxicity. Male and female Sprague Dawley rats were nose-only exposed either to fresh air (sham) or to diluted mainstream smoke from the test, the control, or the Reference Cigarette 1R4F at a concentration of 150 pg total particulate matter/I for 90-days, 6 h/day, 7 days/week. A 42-day post-inhalation period was included to evaluate reversibility of possible findings. There were no remarkable differences in in-life observations or gross pathology between test and control groups. An increase in activity of liver enzymes, known to be due to the high smoke dose, revealed no toxicologically relevant differences between the test and control groups. No toxicological differences were seen between the test and control groups for smoke-related hematological changes, such as a decrease in total leukocyte count. Therefore, NOEC (NOEL) was considered to be 14 ppm when Sprague Dawley rats were exposed to test cigarette smoke by inhalation – nose only route.
Based on the data available from the test chemical, Ethyl formate does not exhibit repeated dose inhalation toxicity. Hence the test chemical is not likely to classify as a repeated dose oral toxicity as per the criteria mentioned in CLP regulation.
Repeated dose dermal toxicity:
Data available for the test chemicals was reviewed to determine the repeated dose oral toxicity of the test chemical. The studies are as mentioned below:
10 weeks repeated dermal study was conducted on male “s” strain mice with the dose concentration of 2760 mg/kg bw/day (0.3ml in acetone applied) and the histopathologic analysis is done to determine the toxic effects. No significant activity was observed In terms of epidermal hyperplasia. Therefore, NOAEL was considered to be 2760 mg/kg bw/day when male “s” strain mice were treated for 10 weeks.
Based on the data available from the test chemical, Ethyl formate (109-94-4) does not exhibit repeated dose dermal toxicity. Hence the test chemical is not likely to classify as a repeated dose dermal toxicity as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the test chemical Ethyl formate (109-94-4) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
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