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EC number: 203-266-8 | CAS number: 105-06-6
- 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:
- chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Repeated dose inhalation toxicity study of the test chemical
- Author:
- Loeser and Litchfield
- Year:
- 1 983
- Bibliographic source:
- Fd Chem. Toxic.
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Repeated dose inhalation toxicity study was conducted to determine the toxic nature of the test chemical
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,4-dichlorobenzene
- EC Number:
- 203-400-5
- EC Name:
- 1,4-dichlorobenzene
- Cas Number:
- 106-46-7
- Molecular formula:
- C6H4Cl2
- IUPAC Name:
- 1,4-dichlorobenzene
- Details on test material:
- - Name of test material: p-Dichlorobenzene- Molecular formula: C6H4Cl2- Molecular weight: 147.0036 g/mol- Substance type: Organic- Physical state: White crystalline compound- Impurities (identity and concentrations): No data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Alderley Park Wistar-derived strain
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: SPF- Age at study initiation:- Weight at study initiation: 150-300 g- Fasting period before study: Overnight- Housing: The animals were housed 9-10/cage- Diet (e.g. ad libitum): No data- Water (e.g. ad libitum): No data- Acclimation period: No dataENVIRONMENTAL CONDITIONS- Temperature (°C): No data- Humidity (%): No data- Air changes (per hr): No data- Photoperiod (hrs dark / hrs light): No dataIN-LIFE DATES: From: To: 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: 2m3 stainless steel chamber- Method of holding animals in test chamber: No data- Source and rate of air: No data- Method of conditioning air: No data- System of generating particulates/aerosols: The test chemical vapour atmospheres were generated by passing clean dry air through p-DCB (99.8".) ill a water-jacketed vessel, which was thermostatically controlled at 55 C- Temperature, humidity, pressure in air chamber: No data- Air flow rate: The required exposure levels were obtained by adjusting the air flow through the test chemical crystals into the exposure chamber- Air change rate: No data- Method of particle size determination: No data- Treatment of exhaust air: No dataTEST ATMOSPHERE- Brief description of analytical method used: The exposure levels were monitored ever 2 3 days rising an infra-red analyser. The overall deviation from themean levels was less than 2%- Samples taken from breathing zone: No dataVEHICLE (if applicable)- Justification for use and choice of vehicle: Air- Composition of vehicle:- Type and concentration of dispersant aid (if powder): No data - Concentration of test material in vehicle: 0 or 100 mg/m3- Lot/batch no. of vehicle (if required): No data- Purity of vehicle: No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 76 weeks
- Frequency of treatment:
- 5 hr/day on 5 days/wk
Doses / concentrations
- Remarks:
- 0 (air control), 75 or 500 ppm (0, 450 or 3000 mg/m3)
- No. of animals per sex per dose:
- 76-79 rats of both sexes
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes- Time schedule: at regular intervals- Cage side observations checked in table [No.?] were included. Clinical condition DETAILED CLINICAL OBSERVATIONS: No data- Time schedule: No dataBODY WEIGHT: Yes - Time schedule for examinations: at regular intervalsFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, at regular intervals- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes- Time schedule for examinations: at regular intervalsOPHTHALMOSCOPIC EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No dataHAEMATOLOGY: Yes- Time schedule for collection of blood: wk 5, 14, 26-27, 40 and 52-53.- Anaesthetic used for blood collection: Yes (identity) / No / No data- Animals fasted: Yes / No / No data- How many animals:- Parameters checked in table [No.?] were examined. Standard parametrsCLINICAL CHEMISTRY: Yes- Time schedule for collection of blood: wk 5, 14. 27, 40 and52.- Animals fasted: No data- How many animals: 5/sex- Parameters checked in table [No.?] were examined. blood urea, blood glucose and plasma alanine and aspartate-transaminase activities. Hepatic aminopyrine-demethylase activity was determined at wk 52 53 on five animals of each sexand groupURINALYSIS: Yes- Time schedule for collection of urine: wk 5, 14. 27, 40 and52.- Metabolism cages used for collection of urine: No data- Animals fasted: No data - Parameters checked in table [No.?] were examined. Urine analyses and urinarycopoporphyrin excretionNEUROBEHAVIOURAL EXAMINATION: No data- Time schedule for examinations: No data- Dose groups that were examined: No data- Battery of functions tested: sensory activity / grip strength / motor activity / other: No dataOTHER: No data
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Rats found dead, killed in extremis or scheduled for interim or terminal kills were subjected to detailed gross examination. Some organ weights were recorded.HISTOPATHOLOGY: Yes, Rats Found dead, killed in extremis or scheduled for interim or terminal kills were subjected to detailed histopathologic examination. Adrenals, aorta, urinary, bladder, caecum, colon, cervix, duodenum, epididymis, heart, ileum, lymph nodes, (cervical, thoracic and mesenteric), jejenum, kidneys, liver, lungs, mammary gland, oesophagus, ovaries, pancreas, prostate, salivary glands, seminal vesicle, spleen, stomach, testes, larynx, trachea, thymus, thyroid, uterus, voluntary muscle, zymbal's gland. Harderian gland, bone (marrow), brain, sciatic nerve, nasal sinuses, pituitary, eye and spinal cord were examined.
- Other examinations:
- Samples of fat, liver, plasma and urine from selected animals ere analysed for metabolites of at wk 26 and 76 and at the termination of the study
- Statistics:
- No data
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No overt signs of exposure-related effect were reported
- Mortality:
- no mortality observed
- Description (incidence):
- The mortality of the exposed rats was similar to that of the control animals throughout the study
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related changes in body weight
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No treatment-related changes in food intake
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- No treatment-related changes in water intake
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Some changes in hematology parameters were observed but found to be independent of treatment
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Some changes in blood biochemistry were observed but found to be independent of treatment. There was also no indication of an increased activity of hepatic aminopyrine demethylase.
- Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Urinary protein and coproporphyrin output was slightly elevated in tile 500-ppm group. This might have been related to functional changes in the liver or kidney, although there was no histological evidence for an effect in these organs
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Liver and kidney weights were increased, giving further evidence of an effect at 500 ppm. Small increases in the weights of heart and lung tit 500 ppm were not related to any histological change and probably did not represent evidence of any effect of treatment. File changes in liver and kidney weights probably indicated milder manifestations of those changes seen at higher exposure levels. Apart from some suggestions of increased liver weight, no changes from control values could be discerned at the 75-ppm level and this dose was considered to be without toxicological effect
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- The rats, except the controls which appeared to be normal, exhibited hemorrhagic areas in the lungs of varying degrees as well as a very bright reddish color to either one or both lungs. The heart was of normal size and color in all animals. The majority showed no liver abnormality with the exception of a few which exhibited white streaks on the surface. The kidneys appeared to be normal except for a few that were swollen.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Description (incidence and severity):
- The animals showed little variation of histological change. Hyperemic and edematous areas were most frequently encountered in the lungs. The epithelium of the bronchi did not appear to be much changed in most cases. Occasionally a dissociation of the epithelium of the bronchi was seen but never very clearly. Fresh hemorrhages in the lungs were observed, mainly in the bronchi. No hypertrophy of the lymphoid tissue was noted. A pyknotic appearance of the nuclei was common. Neither damage to the cells nor hepatitis was observed in the liver sections of the rats. Some hyperemic and edematous areas were seen. All the rats showed extensive damage to the kidneys. The epithelium of the tubules was swollen in most cases. The glomeruli were swollen and hyperemic with very marked pyknosis. Almost all the tubules showed varying degrees of necrobiosis. Some animals showed degeneration and loss of alignment of the nuclei. A few of the animals showed a granular exudate in the collecting tubules. enerally the damage to the kidneys was severe. No definite heart damage was observed. Occasionally an edematous area was noted but the nuclei and striation were intact and visible.
- Description (incidence and severity):
- No treatment-related effect on the incidence of tumours, their multiplicity or malignancy was seen in either tile males or females exposed to test chemical vapour at levels up to 500 ppm.
- Other effects:
- not specified
- Details on results:
- No data
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 3 000 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effects were noted at the mentioned dose level
- Remarks on result:
- other: No effect observed
Target system / organ toxicity
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The No observed adverse effect level (NOAEL) for the test chemical is considered to be 3000 mg/m3.
- Executive summary:
Combined repeated dose & carcinogenicity study was performed to determine the toxic nature of the test chemical. The study was performed using male and female Alderley Park Wistar-derived strain rats. The test chemical was generated in vapor form and exposed to animals at dose levels of0 (air control), 75 or 500 ppm (0, 450 or 3000 mg/m3) for5 hr/day on 5 days/wk in stainless steel containers. During the study, the animals were observed for clinical signs, mortality, changes in body weight, food intake, water intake, hematology, clinical chemistry, urinalysis and subjected to gross and histopathology. No overt signs of exposure-related effect were reported and the mortality of the exposed rats was similar to that of the control animals throughout the study. No treatment-related changes in body weight, food and water intake. Some changes in hematology and blood chemistry parameters were observed but found to be independent of treatment. There was also no indication of an increased activity of hepatic aminopyrine demethylase. Urinary protein and coproporphyrin output was slightly elevated in tile 500-ppm group. This might have been related to functional changes in the liver or kidney, although there was no histological evidence for an effect in these organs. Liver and kidney weights were increased, giving further evidence of an effect at 500 ppm. Small increases in the weights of heart and lung tit 500 ppm were not related to any histological change and probably did not represent evidence of any effect of treatment. Bile changes in liver and kidney weights probably indicated milder manifestations of those changes seen at higher exposure levels. Apart from some suggestions of increased liver
weight, no changes from control values could be discerned at the 75-ppm level and this dose was considered to be without toxicological effect. The rats, except the controls which appeared to be normal, exhibited hemorrhagic areas in the lungs of varying degrees as well as a very bright reddish color to either one or both lungs. The heart was of normal size and color in all animals. The majority showed no liver abnormality with the exception of a few which exhibited white streaks on the surface. The kidneys appeared to be normal except for a few that were swollen. The animals showed little variation of histological change. Hyperemic and edematous areas were most frequently encountered in the lungs. The epithelium of the bronchi did not appear to be much changed in most cases. Occasionally a dissociation of the epithelium of the bronchi was seen but never very clearly. Fresh hemorrhages in the lungs were observed, mainly in the bronchi. No hypertrophy of the lymphoid tissue was noted. A pyknotic appearance of the nuclei was common. Neither damage to the cells nor hepatitis was observed in the liver sections of the rats. Some hyperemic and edematous areas were seen. All the rats showed extensive damage to the kidneys. The epithelium of the tubules was swollen in most cases. The glomeruli were swollen and hyperemic with very marked pyknosis. Almost all the tubules showed varying degrees of necrobiosis. Some animals showed degeneration and loss of alignment of the nuclei. A few of the animals showed a granular exudate in the collecting tubules. Generally the damage to the kidneys was severe. No definite heart damage was observed. Occasionally an edematous area was noted but the nuclei and striation were intact and visible. No treatment-related effect on the incidence of tumours, their multiplicity or malignancy was seen in either tile males or females exposed to test chemical vapour at levels up to 500 ppm. Based on the observations made, the No observed adverse effect level (NOAEL) for the test chemical is considered to be 3000 mg/m3.
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