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EC number: 216-088-0 | CAS number: 1493-27-2
- 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
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Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 06 November To 08 March 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well conducted, sufficiently detailed, according to standardised guidelines, but not GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 976
- Report date:
- 1976
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Male and female rats were exposed to the test substance for 4 hours per day, 6 days per week during 4 weeks. Following the exposure, a rest period of 4 weeks was performed. Hematology examinations were performed at 2, 4, 6 and 8 weeks. Clinical Biochemistry examinations were performed at the end of the exposure (4 weeks). Histology and necropsy were also performed at the end of the exposure.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- 1-fluoro-4-nitrobenzene
- EC Number:
- 206-502-8
- EC Name:
- 1-fluoro-4-nitrobenzene
- Cas Number:
- 350-46-9
- Molecular formula:
- C6H4FNO2
- IUPAC Name:
- 1-fluoro-4-nitrobenzene
- Details on test material:
- - Physical state: pale yellow liquid
- Density: 1.30
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data
Administration / exposure
- 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: Glass chamber
- Exposure chamber volume: 100 L with flow rate of 500L/h
OTHER:
Each day, the product was diluted in ethanol (CAS: 64-17-5)
- Solution (3) = 130 mg/m3 (0.050 ml/heure)
Product 4 ml + ethanol 11.2 ml
- Solution (2) = 40 mg/m3 (0.015 ml/heure)
Product 1.5 ml + ethanol 17.5 ml
- Solution (1) = 130 mg/m3 (0.005 ml/heure)
Dilution 1/10 of solution 3
solution (3) 1 ml + ethanol 9 ml - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 hours
- Frequency of treatment:
- 6 days per week for 4 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
13, 40 and 130 mg/m3 (0.013, 0.04 and 0.13 mg/l)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 8 per dose per sex
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Exposure time: 4 hours, 6 days a week and for 4 weeks, with 4 weeks of reversibility.
After 4 weeks of treatment, 5 males and 5 females per dose were sacrified in order to examine haematology (hemoglobinemia, numeration, erythrocytes and leucocytes), biochemistry (urea and bilirubin) and necropsy.
Other animals were observed during 4 weeks (reversibility).
Haematology was examined after 2 and 4 weeks for animals sacrified after 4 weeks, after 6 and 8 weeks for the others.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: No
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
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: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 2, 4, 6 and 8 weeks
- Anaesthetic used for blood collection: yes
- Animals fasted: No data
- How many animals: 5 per sex at the end of exposure/ 3 per sex after a week of rest.
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the exposure (4 weeks).
- Animals fasted: No data
- How many animals: 5 per sex.
- Parameters checked in table [No.1] were examined.
URINALYSIS: yes
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: YES (Histopatology of heart, lung, liver, spleen, kidneys and adrenal glands was performed)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not examined
- 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:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- 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:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No mortality related to test substance was observed and no clinical signs were reported. One female died due to an anesthesic accident.
HAEMATOLOGY
After 2 weeks of treatment, no effect was observed in all animals. At the end of the exposure (4 weeks), a slight decrease in the erythrocytes count and a significant decrease of leucocytes count at the highest tested doses were observed. In addition, the methemoglobin increased at 40 mg/m3 (3.3 %) and became anormal at the highest tested dose (4.5 %). After two weeks of rest, all parameters showed comparable values to controls. (For details see Table 1)
CLINICAL CHEMISTRY
No significant effect on clinical biochemistry parameters (sodium, potassium, urea, total protein, alkaline phosphatase and alanine aminotransferase) was observed. (For details see Table 2)
GROSS PATHOLOGY
No effect has been observed.
HISTOPATHOLOGY
An effect of the test substance on the spleen was observed. The number of foci of extramedullary hematopoiesis were increased in the red pulpe of the spleen and were accompanied by an increase of splenic hemosiderin and venous sinus congestion. After 4 weeks of rest, foci of hematopoiesis have decreased in all animals. Only clusters of hemosiderin in macrophages were persistant.
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.013 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Effects on spleen
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 0.013 mg/L air (nominal)
- System:
- haematopoietic
- Organ:
- blood
- spleen
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Any other information on results incl. tables
Table 1: Hematologic results
Time | Groups | H % |
Hb g/100 ml |
Erytrocyte E+03/mm3 |
Leucocytes/mm3 | Methemoglobin |
After 2 weeks | Control | 45.2 2.17 |
15.0 0.23 |
7788 584.6 |
11880 3565.4 |
/ |
Control (ethanol) | 44.3 2.34 -0.63 |
15.0 0.55 -0.08 |
7750 245.2 -0.15 |
9466 2498.5 -1.32 |
/ | |
13 mg/m3 | 42.7 1.97 -2.03 |
14.7 0.76 -0.73 |
7113 491.5 -2.1 |
10933 4233.0 -0.39 |
/ | |
40 mg/m3 | 46.0 1.54 0.71 |
15.5 0.52 2.1 |
7503 404.7 -0.95 |
12767 2834.0 0.46 |
/ | |
130 mg/m3 | 44.1 2.40 -0.74 |
14.7 0.86 -0.65 |
7450 395.7 -1.1 |
12917 2324.0 0.53 |
/ | |
After 4 weeks | Control | 49.3 2.9 |
15.8 1.0 |
8777 886 |
19289 33250 |
2.36 0.45 |
Control (ethanol) | 48.3 1.88 -0.93 |
15.3 0.87 -1.13 |
8494 552 -0.85 |
15070 2865 -2.97 |
2.57 0.35 1.09 |
|
13 mg/m3 | 46.6 (-) 1.90 -2.44 |
15.0 0.76 -1.96 |
7940 (-) 642 -2.38 |
13930 (--) 2735 -3.85 |
2.87 (+) 0.53 2.35 |
|
40 mg/m3 | 46.9 2.38 -2.0 |
14.8 (-) 0;69 -2.4 |
8004 (-) 436 -2.46 |
12570 (---) 1865 -5.50 |
3.25 0.41 4.65 (+++) |
|
130 mg/m3 | 45.2 (--) 2.1 -3.57 |
14.4 (-) 0.99 -2.97 |
7724 (-) 676 -2.93 |
11510 (---) 1995 -6.26 |
4.54 0.91 6.76 (+++) |
|
After 6 weeks | Control | 45.3 4.3 |
15;6 0.23 |
8183 368 |
9983 1762 |
/ |
Control (ethanol) | 50.0 1.8 1.77 |
16.0 0.34 2.08 |
7866 457 -1.32 |
10516 2125 0.47 |
/ | |
13 mg/m3 | 49.0 1.8 1.94 |
15.9 0.64 0.83 |
7953 573 -0.83 |
11867 4694 0.92 |
/ | |
40 mg/m3 | 49.8 2.9 2.14 |
15.3 0.56 -1.21 |
2270 423 0.38 |
10767 1261 0.89 |
/ | |
130 mg/m3 | 49.3 2.7 1.93 |
15.5 0.27 -0.68 |
8133 242 -0.28 |
9500 1445 0.52 |
/ | |
After 8 weeks | Control | / | / | 7753 380 |
/ | 2.58 0.62 |
Control (ethanol) | / | / | 7460 535 -1.06 |
/ | / | |
13 mg/m3 | / | / | 7810 460 0.23 |
/ | / | |
40 mg/m3 | / | / | 8013 373 1.19 |
/ | / | |
130 mg/m3 | / | / | 7670 259 -0.44 |
/ | 1.97 0.30 -2.20 |
Statistically significant from control at : 95 % (+ or -), 99 % ( ++ or --), 99.9 % (+++ or ---)
Table 2: Chemical biochemistry results
Groups | Na mEq/l | K mEq/l | Urea g/l | Bilirubin mg/l | Proteins g/l | alkaline phosphatase | alanine aminotransferase |
Control | 147.0 2.2 |
6.1 0.8 |
0.44 0.10 |
0.47 0.28 |
61.7 4.0 |
331 89 |
94* 62 |
Control (ethanol) | 147.0 2.0 |
6.0 0.6 |
0.45 0.17 |
0.34 0.23 |
61.2 1.2 |
346 36 |
58 18 |
13 mg/m3 | 147.6 2.2 |
5.4 0.3 |
0.40 0.12 |
0.80 0.30 |
59.0 4.3 |
322 91 |
50 7 |
40 mg/m3 | 148.5 2.1 |
6.2 0.4 |
0.42 0.07 |
0.81 0.13 |
56.0 7.1 |
301 27 |
104* 151 |
130 mg/m3 | 149.0 4.1 |
5.6 0.4 |
0.46 0.07 |
0.97 1.34 |
56.6 4.2 |
296 31 |
70 44 |
* Elevated medium due to an outlier.
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this test, the test substance showed a toxic effect at the blood cell level.
- Executive summary:
Male and female rats were exposed to the test substance for 4 hours per day, 6 days per week during 4 weeks. Following the exposure, a rest period of 4 weeks was performed. Hematology examinations were performed at 2, 4, 6 and 8 weeks. Clinical Biochemistry examinations were performed at the end of the exposure (4 weeks). Histology and necropsy were also performed at the end of the exposure. Animals were exposed at 13, 40 or 130 mg/m3 of the test substance. No mortality related to test substance was observed and no clinical signs were reported. One female died due to an anesthesic accident. After 2 weeks of treatment, no effect was observed in all animals. At the end of the exposure (4 weeks), a slight decrease in the erythrocytes count and a significant decrease of leucocytes count at the highest tested doses were observed. In addition, the methemoglobin increased at 40 mg/m3 (3.3 %) and became anormal at the highest tested dose (4.5 %). After two weeks of rest, all parameters showed comparable values to controls. No significant effect on clinical biochemistry parameters (sodium, potassium, urea, total protein, alkaline phosphatase and alanine aminotransferase) was observed. No gross pathologic effect has been observed. An effect of the test substance on the spleen was observed. The number of foci of extramedullary hematopoiesis were increased in the red pulpe of the spleen and were accompanied by an increase of splenic hemosiderin and venous sinus congestion. After 4 weeks of rest, foci of hematopoiesis have decreased in all animals. Only clusters of hemosiderin in macrophages were persistant. Under the conditions of this test, the test substance showed a toxic effect at the blood cell level.
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