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EC number: 200-842-0 | CAS number: 75-12-7
- 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
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- Nanomaterial aspect ratio / shape
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- Endpoint summary
- Stability
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- 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:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comprehensive, well documented study comparable to guideline study. Restriction: heating the TS to 180-240°C may cause test substance degradation which was not examined in this study.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Inhalation toxicity study of formamide in rat.
- Author:
- Warheit DB, Kinney LA, Carakostas MC, and Ross PE
- Year:
- 1 989
- Bibliographic source:
- Fund. Appl.Toxicol. 13, 702-713.
- Report date:
- 1989
- Reference Type:
- other: TSCATS
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- no
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Formamide
- EC Number:
- 200-842-0
- EC Name:
- Formamide
- Cas Number:
- 75-12-7
- Molecular formula:
- CH3NO
- IUPAC Name:
- formamide
- Details on test material:
- purity >99 %, obtained from Aldrich Chem.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD BR
- Sex:
- male
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: air/nitrogen
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The atmospheric concentration of formamide in each exposure chamber was determined at approximately 45-min intervals during each exposure. Samples of the chamber atmospheres were collected in duplicate from the rats' breathing zones with tandem midget impingers containing methanol as a trapping solvent. Each sample was injected into a Hewlett- Packard 5880 gas chromatograph equipped with a flame ionization detector. Samples were chromatographed isothermally at 70°C on a 30mx 0.53-mm i.d . poly dimethyl siloxane Megabore column. The atmospheric concentration of formamide was determined by comparing peak areas with standard curves calculated daily. Standard samples were prepared at least weekly by diluting a known amount of liquid formamide in a volumetric flask containing methanol.
- Duration of treatment / exposure:
- 2 weeks
- Frequency of treatment:
- 5 days/week; 6 hours/day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
ca. 0.19, 0.93, 2.8 mg/l (100, 500, 1500 ppm)
Basis:
- No. of animals per sex per dose:
- 10 males/dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: 2 weeks
- Positive control:
- not required
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: daily
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day 12 after 10 exposures (5/sex/dose) or at the end of the 14-day recovery period (5 rats/sex/dose)
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
- Parameters examined: erythroctye count; kematokrit; hemnoglobin; platelet count; total and diffeerntial leucocyte count.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day 12 after 10 exposures (5/sex/dose) or at the end of the 14-day recovery period (5 rats/sex/dose)
- Animals fasted: No data
- How many animals: all
- Parameters examined: Serum samples were analyzed for alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activity and for concentrations of urea nitrogen, creatinine, total protein, and cholesterol .
URINALYSIS: Yes
- Time schedule for collection of urine: 9th day of exposure, and 13th day of recovery
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: Samples were analyzed for volume, osmolality, and standard biochemical parameters using a commercially available urine dipstick (Multistix, Ames Division, Miles Laboratories, Elkhart, IN) . The sediment from each sample was also examined microscopically . - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- Mean body weights and body weight gains for test rats were compared to controls during the exposure and recovery periods. Data were statistically analyzed by one-way analysis of variance (ANOVA). Exposure group values were compared to controls by the least significant difference test and Dunnett's test when the ratio of variance (F) indicated a significant among-to-within group variation . Significant differences were declared at the 0 .05 probability level .
For analysis of clinical measurements, ANOVA and Bartlett's test were calculated for each sampling time . When the F-test from ANOVA was significant, Dunnett's test was used to compare means from the control groups and each of the groups exposed to formamide.
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 specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 0.19 other: mg/l
- Sex:
- male
- Basis for effect level:
- other: hematologic and clinico-chemical parameters measured at 500 and 1500 ppm (in particular thrombocytopenia)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
A. SURVEY/SUMMARY:
The NOAEC for repeated inhalation of formamide in rats was considered to be 100 ppm, based on the hematologic and clinico-chemical parameters measured at 500 and 1500 ppm (in particular thrombocytopenia) [table 4, p. 707]. The biological relevance of this effect was considered equivocal, because histopathological examination of bone marrow in all groups failed to demonstrate any alterations in megakaryocytopoiesis which might confirm TS-related, suppressive effects on platelet production.
The NOAEC based on histopathologic changes was 500 ppm.The study clearly showed that 10 repeated exposures to doses higher than 500 ppm produced nephrotoxicity and that the liver apparently was not affected (contrary to dimethyl formamide) [p. 713]. It was evident that the growth rate was normal up to 500 ppm, that, however, the high toxic dose of 1500 ppm markedly depressed body weight, which continuously decreased at about 20 % after 10 exposures and did not catch up until 6 d after termination of treatment, but then at a growth rate similar to that of the other groups [Plot p. 705].
B. FURTHER
DETAILS:
Mortality:
During the study, two of the rats in the highest dose group died (on
test days 3 and 9); another rat was sacrificed in extremis on test day
11.
Body weights: The body weights and body weight gains of rats
exposed to 1500 ppm were statistically significantly depressed compared
to controls. No differences in body weight and body weight gains were
observed in the other treated groups.
Clinical signs of toxicity:weakness, hunched postures were
observed in the 1500 ppm group only, while low incidences of diarrhea
occurred in all groups.
Clinical
pathologic examination revealed mild thrombocytopenia in rats
exposed to 500 and 1500 ppm after 10 days of exposure and during the
recovery period. Additionally, lymphopenia and slight
hypocholesterolemia was observed in the high-dose group; lymphopenia was
statistic- ally significant and persisted after 14 days of recovery.
Histopathology: In the high-dose rats only, pathological examinations revealed compound-related minimal to severe zonal nephrosis in the inner cortex and outer medulla, characterized by necrosis and regeneration of the renal tubular cells with all tubular segments affected in the deep cortical nephrons. After the 14-days recovery period, the mild renal lesions consisted of regeneration of the tubular epithelium with no necrosis present. Presumably due to the pronounced weight loss, kidney-to-body ratios were significantly elevated in the highest dosed group. But absolute kidney weights were increased, too, but not statistically significant, at the end of the exposure period. After 14 days of recovery, absolute and relative kidney weights were statistically significantly elevated.
C. Addendum
PATHOLOGY:
Although
apparently elevated as compared to the control and low-dose groups, a
number of changes diagnosed microscopically in the 1500-ppm group were not
considered to be
compound-related
- depletion
of lymphocytes in spleen, thymus, lymph nodes;
-
gastric erosion;
-
degeneration of seminiferous epithelium in the testes;
-
atrophy in bone marrow.
3/5 animals of the 1500-ppm group vs. none or 1/5 in other groups exhibited degeneration in the testicular epithelium [publication, Tab. 3, p. 707].
Applicant's summary and conclusion
- Executive summary:
In an inhalation study that was conducted similar to OECD TG 412, three groups of 10 male CrLCD BR rats each were exposed nose-only for 6 hr/day, 5 days/week for 2 weeks to design concentrations of 100, 500, or 1500 ppm of formamide aerosol in air. A control group of 10 male rats was exposed simultaneously to air only. 50% of the animals were sacrificed on study day 12 after 10 exposures, the remaining animals were allowed a 14 day recovery. Statistically significantly reduced body weights, histopathological changes in the kidneys, and reduced platelet counts were seen in rats at 1500 ppm. Rats at 500 ppm showed reduced platelet counts only.
The NOAEC for repeated inhalation of formamide in rats was considered to be 100 ppm or 0.19 mg/kg bw/day, based on the hematologic and clinico-chemical parameters measured at 500 ppm (in particular thrombocytopenia). The biological relevance of this effect was considered equivocal. 100 ppm corresponds to 0.187 mg/L [which is far above the vapour saturation concentration of 0.055 mg/L], or 54 mg/kg bw/d, calculated on the basis of default physiological parameters [R8, page 26: rat body weight: 0.25 kg; rat respiratory volume, 6h: 0.29 m³).
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