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EC number: 701-284-5 | CAS number: 2137881-70-8
- 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

Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- August 1987 - September 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study. Range-finding study, findings to be considered together with the main study.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 989
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 992
Materials and methods
- Principles of method if other than guideline:
- GLP guideline study. 14-day range-finding study
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Formic acid
- EC Number:
- 200-579-1
- EC Name:
- Formic acid
- Cas Number:
- 64-18-6
- Molecular formula:
- CH2O2
- IUPAC Name:
- formic acid
- Details on test material:
- 95 % formic acid / 5 % water
- Name of test material (as cited in study report): formic acid
- Physical state: liquid
- Analytical purity: 95%
- Impurities (identity and concentrations): water. Formaldehyde: <0.1%
- Composition of test material, percentage of components: 95% formic acid, 5% water
Constituent 1
- Specific details on test material used for the study:
- 95 % formic acid / 5 % water
- Name of test material (as cited in study report): formic acid
- Physical state: liquid
- Analytical purity: 95%
- Impurities (identity and concentrations): water. Formaldehyde: <0.1%
- Composition of test material, percentage of components: 95% formic acid, 5% water
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Farms, Inc., Germantown, NY
- Age at study initiation: 6 wks (7 weeks for mice in 13-week studies)
- Housing: individually
- Diet: standard NIH-07 diet ad libitum
- Water: tab water ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature 75°F
- Humidity (%): rel. humidity 55+/-15%,
- air changes per hour: 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: commercial 1.7 m³ inhalation chambers
- Temperature, humidity, pressure in air chamber: temperature 75°F, rel. humidity 55+/-15%
- Vapor generation: liquid formic acid was pumped by a micrometer pump to a vaporizer heated to 97.5°C. The vapor entered a distribution line where a constant 2300 ppm atmosphere was maintained. Dilution air (HEPA filtered, rel. humidity 50%) carried a metered amount to the individual exposure chambers.
TEST ATMOSPHERE
- Brief description of analytical method used: a Foxboro Mitran 980 infrared spectrometer at 9.050 microns was used to monitor the exposure chambers, control chamber, exposure room, an online standard of formic acid vapor, and a pure nitrogen source. All locations were monitored every 40 min. In addition, formaldehyde concentrations were monitored in the 8 ppm and 128 ppm exposure chambers, and in the formic acid distribution line. Corrections were made for absorbance of water and for instrument drift.
The online monitor was calibrated with GC analyses of grab samples taken from teh exposure chambers at the time of the readings.
The limit of detection and limit of quantification for the on-line monitor were determined at an average chamber relative humidity of 33-51%.
The practical detection limit was 0.36 ± 0.10 ppm, with a practical quantification limit of 0.68 ± 0.10 ppm.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- A Foxboro Mitran 980 infrared spectrometer at 9.050 microns was used to monitor the exposure chambers, control chamber, exposure room, an online standard of formic acid vapor, and a pure nitrogen source. All locations were monitored every 40 min. In addition, formaldehyde concentrations were monitored in the 8 ppm and 128 ppm exposure chambers, and in the formic acid distribution line. Corrections were made for absorbance of water and for instrument drift. The online monitor was calibrated with GC analyses of grab samples taken from the exposure chambers at the time of the readings.
The limit of detection and limit of quantification for the on-line monitor were determined at an average chamber relative humidity of 33-51%. The practical detection limit was 0.36 ± 0.10 ppm, with a practical quantification limit of 0.68 ± 0.10 ppm. - Duration of treatment / exposure:
- 12 days
- Frequency of treatment:
- 5 days/week, 6 h/day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0; 0.06; 0.12; 0.24; 0.48; 0.95 mg/l (0; 31; 62.5; 125; 250; 500 ppm)
Basis:
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
- Dose selection rationale: based on rangefinding study
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: recorded on a weekly base
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 3 and at termination
- Animals fasted: No data
- How many animals: 5/sex/dose
URINALYSIS: Yes
- Time schedule for collection of blood: day 3 and at termination
NEUROBEHAVIOURAL EXAMINATION: No
- Gross pathology: YES
- Time schedule: at termination
- How many animals: 5/sex/dose
Histopathology: Yes
The following tissues were examined microscopically: lungs, trachea, larynx, bronchial lymph nodes, nose
(three transverse sections), and all gross lesions from all treated and control animals.
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- Coagulation
- Statistics:
- not specified
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- 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:
- not examined
- Clinical biochemistry findings:
- not examined
- 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:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Mortality: all mice exposed to 500 ppm of formic acid died during the first week of the study; a female of the 250 ppm group was killed moribund on day 4 of exposure.
Clinical signs: nasal discharge, increased preening, and labored breathing in the 250 and 500 ppm groups.
BODY WEIGHT AND WEIGHT GAIN
Body weight gain: significantly lower than in controls from day 42 onwards, terminal body weight of males 81% (females 84%) compared to controls.
ORGAN WEIGHTS
Small increases (~ 10%) in the relative kidney weight in males at 62.5. 125, and 250 ppm and in female exposed to 250 ppm were reported. Reduced absolute and relative thymus weight was seen in mice exposed to 250 ppm; relative lung weights were slightly increased in these groups.
GROSS PATHOLOGY
there were no gross lesions. Dried exudates was noted around the nares of all mice at 500 ppm and 1 female at 250 ppm during the first week of the study. The stomach and small intestines were distended with air in animals that died. Distension was attributed to swallowing air during mouth breathing which was enforced by the swelling and occlusion of the nasal passages.
HISTOPATHOLOGY: NON-NEOPLASTIC
Histopathological lesions were similar in male and female mice. They were limited to the nasal passages, except at the 500 ppm level where they wear also present in the larynx, pharynx, and trachea. The incidence and severity increased with dose. At 32 and 62.5 ppm the histopathological findings were limited to mild squamous metaplasia of the respiratory epithelium in 2 females.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 0.06 mg/L air
- Sex:
- male/female
- Basis for effect level:
- other: histopathological changes in the respiratory tract
- Dose descriptor:
- LOAEL
- Effect level:
- 0.12 mg/L air
- Sex:
- male/female
- Basis for effect level:
- other: histopathalogical changes in the nose
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Exposure concentration: during the 2-week and the 13-week studies, at least 96% and 91%, respectively, of the measured concentrations
for each chamber were within ± 10% of the target concentration.
Histopathology detail information:
==========================================================
Exposure concentration (ppm)
0 31 62.5 125 250 500
----------------------------------------------------------
Males
NOSE
Respiratory epithelium
squam. metaplasia 0 0 0 3(1.3) 4(1.3) 1(1.0)
inflammation 0 0 0 2(1.0) 4(1.2) 5(1.4)
necrosis 0 0 0 0 0 4(3.5)
Olfactory epithelium
degeneration 0 0 0 0 3(1.3) 1(2.0)
necrosis 0 0 0 0 0 3(2.0)
LARYNX
squam. metaplasia 0 0 0 0 0 5(2.8)
inflammation 0 0 0 0 0 3(1.0)
PHARYNX
necrosis 0 0 0 0 0 3(2.0)
Females
NOSE
Respiratory epithelium
squam. metaplasia 0 0 2(1.0) 3(1.3) 4(1.0) 0
inflammation 0 0 0 2(1.5) 5(1.4) 5(1.8)
necrosis 0 0 0 0 2(1.5) 5(3.6)
Olfactory epithelium
degeneration 0 0 0 0 2(2.0) 0
necrosis 0 0 0 0 1(1.0) 5(1.8)
LARYNX
squam. metaplasia 0 0 0 0 0 1(2.0)
inflammation 0 0 0 0 0 3(1.0)
necrosis 0 0 0 0 0 5(2.2)
PHARYNX
necrosis 0 0 0 0 0 2(1.0)
==========================================================
Average grade of severity is given in brackets:
1=minimal ; 2=mild; 3=moderate; 4=marked
The NOAEC in this study was determined to be 32 ppm (0.06 mg/l), based on histopathological changes in the respiratory tract.
Applicant's summary and conclusion
- Executive summary:
Mortality was complete at 500 ppm of formic acid within one week. At 250 ppm, one female died and body weight was significantly decreased by 16 to 19% compared to controls.
Systemic toxicity was generally low. Findings during histopathology consisted of squamous metaplasia of the respiratory and olfactory epithelium in groups at 125 ppm and above. The incidence and severity increased with dose. Squamous metaplasia and inflammation in larynx, and necrosis in pharynx, were seen in animals at 500 ppm.
The NOAEC in this study was determined to be 32 ppm (0.06 mg/l), based on histopathological changes in the respiratory tract (2 cases of mild respiratory epithelium squamous metaplasia in females at 62.5 ppm). Mice were more susceptible than rats exposed to formic acid under the same conditions.
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