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EC number: 201-187-3 | CAS number: 79-22-1
- 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:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP Guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
- Reference Type:
- other: Notification
- Title:
- No information
- Author:
- BASF Corp.
- Year:
- 1 993
- Bibliographic source:
- US EPA; TSCATS: 8ECP, Doc. I.D: 88-930000347
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Methyl chloroformate
- EC Number:
- 201-187-3
- EC Name:
- Methyl chloroformate
- Cas Number:
- 79-22-1
- Molecular formula:
- C2H3ClO2
- IUPAC Name:
- methyl chloroformate
- Details on test material:
- - Name of test material (as cited in study report): Chloroformic aci methyl ester
- Physical state: colorless liquid
- Analytical purity: 99.2%
- Expiration date of the lot/batch: 1990-10-31
- Stability under test conditions: stable
- Storage condition of test material: dark at room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charle River (USA)
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 1180-195 (males), 144-159 (females)
- Fasting period before study: no
- Housing: in groups of five
- Diet (e.g. ad libitum): ad libitum, except at exposure (Biosure diet LAD1 Lavander Mill, Manea, England)
- Water (e.g. ad libitum): ad libitum, except at exposure
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 30 - 61 %
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Vapor generation: Vapor was generated by metering the test material to a sintered glass disc through which air was passed. The vapor was carried to a stainless steel manifold fitted with 5 T junctions containing metering valves. Delivery of vapor to each of the exposure chambers was controlled by each of the metering valves. The vapor entered the chamber at the top via the inlet air duct. Waste vapor was removed by passage through activated charcoal.
Exposure chambers were constructed form stainless steel and glass and had an internal volume of approximately 2.4 m³. Inlet air (650 lpm) was introduced into the inlet duct set at a tangent into the top of each chamber. Air flow was monitored continuously by measuring the pressure differential across a venturi nozzle set into the air inlet of each chamber. Chamber pressure was monitored continously using a magnehelic pressure gauge and recorded at approximately 30-minute intervals. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Continuous infra-red monitoring of each chamber allowed for adjustments to be made so that target concentrations could be reached.
Concentrations present in each chamber were recorded at least hourly. Samples of test atmosphere were withdrawn from each chamber into the sample loop of one of two infra-red gas analyzers. The absorbance at a known wavelength was measured and recorded by a flat-bed chart recorder. Due to the system design and the loss of a significant proportion of the vapor through the exhaust line, it was not possible to calculate nominal concentrations. - Duration of treatment / exposure:
- 28 Tage
- Frequency of treatment:
- 5 Tage/Woche; 6 Std/Tag
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0 (air) 0.52; 1.48; 3.94; 12.14; 34.46 mg/m³
Basis:
analytical conc.
- Remarks:
- Doses / Concentrations:
0 (air), 0.5, 1.5, 4.0, 12.0 or 35.0 mg/m³
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: no
- Positive control:
- not necessary
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
WATER CONSUMPTION: Yes
HAEMATOLOGY: Yes
Samples of blood were collected from the orbital sinus under light ether anesthesia from all rats during week 4. All rats were fasted the night before blood collection.
Parameters: measured in the blood included packed cell volume, hemoglobin, red cell count, mean corpuscular hemoglobin concentration, mean corpuscular volume, mean corpuscular, hemoglobin, total and differential white blood cell counts, thrombotest.
CLINICAL CHEMISTRY: Yes
Samples of blood were collected from the orbital sinus under light ether anesthesia from all rats during week 4. All rats were fasted the night before blood collection.
Parameters measured in the plasma for glucose, glutamic-pyruvic transaminase, glutamic-oxaloacetic, transaminase, total protein, albumin, globulin, albumin/globulin ratio, urea nitrogen, alkaline phosphatase, total bilirubin, creatinine, sodium , potassium, calcium, inorganic phosphorus, chloride, and cholesterol
- Sacrifice and pathology:
- Sacrifice:
After the 28-day exposure period, all rats were sacrificed over 2 days. Those rats not sacrificed on the first day received an additional exposure.
The following tissues were fixed: adrenals, aorta, brain, cecum, colon, duodenum, eyes, eyelids, exorbital lachrymal gland, femur with joint, Harderian gland, head (nasal passages), heart, ileum, jejunum, kidneys, larynx, liver, lungs, lymph nodes (cervical, mediastinal and tracheobronchial), mammary glands, esophagus, optic nerve, ovaries, oviduct, pancreas, pharynx, pituitary, prostate, rectum, salivary gland, sciatic nerve, seminal vesicles, skeletal muscle, skin, spinal column, spinal cord (entire), spleen, sternum/ribs, stomach, testes (with epididymides), thymus, thyroids (with parathyroids), tongue, trachea (with bifurcation), ureter, urinary bladder, uterus and vagina.
Sections of the adrenals, masal passages, heart, kidneys, larynx, liver, lungs, spleen and trachea were examined microscopically.
The brain, lungs, testes (male), ovaries (female), pituitary, adrenals, liver adn kidneys were examined grossly and weighed. - Statistics:
- All statistical analyses for male and females were carried out separately. Bartlett's test (Proc Roy Soc A 160:268-282, 1937) for heterogeneity of variance was applied to the data. If significant, data were log transferred. If no significant heterogeneity was found or if the transformation was satisfactory, data were analyzed by one-way analysis of variance (ANOVA), followed by the Student's t-test and Williams' test (Biometrics 27:103-117 and 28:519-531, 1952/3). The Kruskal-Wallis analysis of ranks (J Amer Statis Ass 47:583-621 and 48:907-912) was used to analyze heterogeneous data. These data were further analyzed by the Shirley's test (Biometrics 33: 386-389, 1977). Analysis of covariance was used in place of ANOVA for organ weight data (with body weight as the covariant) in an attempt to negate the influence of body weight on organ weight.
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):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- local
- Effect level:
- 3.94 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: --
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 12.14 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: --
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
35 mg/m³: Two males and 1 female exposed to 34.46 micrograms/ml died prior to blood sampling during the final week of exposure. Clinical signs observed during
exposure
included blinking, hunched posture and rapid breathing. Rats
in this group had noisy, apparently nasal breathing between exposures. Rats
surviving to study termination had a rapid breathing pattern. Males and
females had reduced weight gain for the first 2 weeks of exposure.
Animals that died lost weight between weeks 2 and 3. A marked reduction
in food consumption occured during the first 2 weeks of exposure.
Results of hematological studies showed increased
packed cell volume, hemoglobin concentration, and numbers of red blood
cells (both males and females), neutrophils (females and 1/3 of the
males), eosinophils (males) and monocytes (males). Mean
corpsucular hemoglobin concentration and mean corpsucular hemoglobin
were slightly decreased in males. Results of biochemical analyses showed
increased total protein in males and increased globulin and cholesterol,
decreased albumin, and a decreased albumin/globulin ratio in both sexes. Small
changes in electrolytes were within normal ranges and therefore were not
concsidered to be significant. The following pathological changes were
seen in rats killed after 4 weeks of exposure: lungs that did not
collapse upon opening of the thoracic cavity (3/3 males and 4/4
females), congestion of the lungs (1/3 males and 1/4 females), enlarged
mediastinal lymph nodes (3/3 males and 3/4 females), and enlarged
tracheobronchial lymph nodes (3/3 males and 3/4 females). Similar
findings were seen in the animals that died before study termination.
Lung weights of males and females and adrenal weights of males were
increased. Pituitary and ovary weights of females were decreased.
Microscopic examinations revealed exudative sinusitis in the nasal
turbinates of 4/5 males and 5/5 females (but no evidence of degenerative
or erosive lesions); localized areas of minimal squamous metaplasia of
the epithelia overlying the arytenoid processes of the larynx in 3/5
males and 4/5 females (with occasional areas of ventral epithelial
erosion and inflammation in some rats); localized squamous metaplasia of
the ventral epithelia of the larynx in 3/5 females; minimal inflammatory
changes with some minimal epithelial hyperplasia in the trachea (1/5
males); minimal to marked areas of pneumonitis in the lungs with
intra-alveolar
exudation and aggregation of alveolar macrophages (all males and
females); brohchiolitis (number of animals was not stated); squamous
metaplasia of terminal bronchilar
epithelia with occasional focal necrosis, edema and congestion (number
of animals was not stated); and granulomatous lesions (1 female).
12.0 mg/m³: One male rat had noisy nasal breathing for 4 days during
week 2 of exposure. Minor, localized squamous metaplasia of laryngeal
arytenoid process epithelia
was noted in 2/5 males and 1/5 females. One female had exudative
sinusitis.
4.0 mg/m³
:
Minor, localized squamous metaplasia of laryngeal arytenoid process
epithelia was noted in 1/5 males.
1.5 mg/m³:
No effects were observed.
0.5 mg/m³
: No
effects were observed.
Control: Focal squamous metaplasia of laryngeal arytenoid process
epithelia was noted in 1/5 females
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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