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EC number: 202-804-9 | CAS number: 99-96-7
- 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
- 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
- Study period:
- days of exposure: Feb 15 - Feb 26 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: acceptable, well-documented study which meets basic scientific principles
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- 12 day inhalation toxicity study
- GLP compliance:
- no
Test material
- Reference substance name:
- 4-hydroxybenzoic acid
- EC Number:
- 202-804-9
- EC Name:
- 4-hydroxybenzoic acid
- Cas Number:
- 99-96-7
- Molecular formula:
- C7H6O3
- IUPAC Name:
- 4-hydroxybenzoic acid
- Details on test material:
- - Name of test material (as cited in study report): C-194
- Substance type: white powder
- Physical state: solid
- Analytical purity: approximately 100%
- Expiration date of the lot/batch: February 9, 1982
- Supplier: Celanese Corporation, 1211 Avenue of the Americas, New York, New York 10036
Comment by the applicant:
Existing retained samples from batches of C-194 of 1981 were analytically rechecked. The identity was confirmed with a content of 4-HBA of approximately 100% (NMR analysis).
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Sprague-Dawley derived CD
- Source: Charles River Breeding Laboratories, Kingston, New York
- Age at study initiation: males: 41 days; females: 57 days
- Weight at study initiation: males: (mean: 198) 192-210 g; females: (mean: 183) 173-197 gram
- Fasting period before study: no
- Housing:Individual in hung stainless steel, wire mesh-bottom cages
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow (5001) ad libitum
- Water (e.g. ad libitum):Citx-tap water (Elizabethtown Water Co.) ad libitum
- Acclimation period: 12 days
Administration / exposure
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:glas chamber
- Method of holding animals in test chamber: individual stainless steeel, wire mesh cages
- Air: dry air at a pressure of 5 psi
- System of generating particulates/aerosols: Wright Dust Feed Mechanism
- Air flow rate: 155-245 liters per minute
- Air change rate: every 6.5 - 4.1 minutes
TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric sampling, particle size distribution: Batelle cascade impactor
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- gravimetric control of the total airborne concentration
- Duration of treatment / exposure:
- exposure of 6 hours per day on 5 consecutive days, 2 days interruption and another 5 days exposure for 6 hours per day
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 20, 60, 200 mg/m³
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5 per sex and dose
- Control animals:
- yes, concurrent no treatment
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice weekly
BODY WEIGHT: Yes
- Time schedule for examinations: before and after exposures 1, 5 and 10.
HAEMATOLOGY: Yes
- Time schedule for collection of blood:before the last exposure period:
- Parameters checked: hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before and after exposures 1, 5 and 10.
- How many animals: control and high dose animals
- Parameters checked: blood urea nitrogen, serum glutamic pyruvic transaminase, glucose, total protein. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes: kidneys, liver, lungs, nasal passages, trachea - Statistics:
- The animals were randomly distributed to the groups.
Body weights, organ weights, and organ/body weight ratios were statistically evaluated. Statistical evaluation of equality of means was made by the appropriate one way analysis of variance technique, followed by a multiple comparison procedure if needed.
hematology and clinical chemistry: To statistically determine if the two means were equal, first, test if the variances of the two groups could be considered as equal. If the variances were equal a standard, independent, two sample t-test was used to determine the equality of means. If the variances differed, Welch's t-test was used to determine equality of means.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- for effects see below
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- 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 specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY
overall effects: increased instances of dried material around the facial area were detected in all exposure groups,
high dose only (200 mg/m³): ocular irritation (swollen eyelids, injection of conjunctival blood vessels),
hematology: males: elevated hematocrit, reduction in MCHC values, depressed clotting time
histopathology: 2 males, 1 female: increased mitotic activity of parenchymal liver
BODY WEIGHT: no effect
HAEMATOLOGY: 200 mg/m³, males: elevated hematocrit, reduction in MCHC values
CLINICAL CHEMISTRY: 200 mg/m³, males: depressed clotting time
ORGAN WEIGHTS: no effect
GROSS PATHOLOGY: no test article related effects
HISTOPATHOLOGY: 200 mg/m³: 2 males, 1 female: increased mitotic activity of parenchymal liver
Particle size distribution:
- Aerodynamic mass median diameter (group II, III, IV) in µm/ % of Particles 10 µm or less in diameter: 4.74; 5.55; 6.26/ 73.51; 77.47; 70.39
Effect levels
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 60 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: clinical signs; hematology; clinical chemistry; histopathology
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 200 mg/m³ air
- System:
- respiratory system: upper respiratory tract
- Organ:
- blood
- cornea
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- presumably yes
Any other information on results incl. tables
overall effects:
Increased instances of dried material around the facial area were detected in all exposure groups,
high dose only (200 mg/m³): ocular irritation (swollen eyelids, injection of conjunctival blood vessels)
clinical signs: males: elevated hematocrit, reduction in MCHC values, depressed clotting time,
histopathology: 2 males, 1 female: increased mitotic activity of parenchymal liver
Applicant's summary and conclusion
- Conclusions:
- An inhalation toxicity study was performed using 4 groups, one control and 3 dose groups, of 5 male and 5 female Sprague-Dawley rats each exposed to C-194, all in all 40 animals. The exposure period lasted for 6 hours per day for 5 days followed by another 5 day exposure period after an interruption of 2 days. The cumulative mean measured/nominal exposure concentrations were: 23.8, 64.0 and 189 mg/m³; 20, 60 and 200 mg/m3.
Physical examinations revealed increased instances of dried material around the facial area in all exposure groups.
20 mg/m³: no differences to the data of the control animals,
60 mg/m³: no differences to the data of the control animals,
200 mg/m³: The observed changes can be explained by an irritative effect of 4 -HBA to the eyes and in the respiratory tract specially in the nose and the lungs and a possible toxic effects on the liver and on the blood. - Executive summary:
An inhalation toxicity study was performed using 4 groups, one control and 3 dose groups, of 5 male and 5 female Sprague-Dawley rats each exposed to C-194, all in all 40 animals. The exposure period lasted for 6 hours per day for 5 days followed by another 5 day exposure period after an interruption of 2 days. The cumulative mean measured/nominal exposure concentrations were: 23.8, 64.0 and 189 mg/m³; 20, 60 and 200 mg/m3.
Physical examinations revealed increased instances of dried material around the facial area in all exposure groups.
20 mg/m³: no differences to the data of the control animals,
60 mg/m³: no differences to the data of the control animals,
200 mg/m³: swollen eyelids (6 animals day 2), area around the eye swollen (1 animal day 9), injection of conjunctival blood vessels (5 animals on day 12)
clinical chemistry: males: elevated hematocrit, reduction in MCHC values;
hematology: males: depressed clotting time
histopathology: Lungs: chronic interstitial pneumonia, 2 males, 2 females; partial atelectasis: 2 females; perivascular edema/cellular infiltrate: 1 female; alveolar septa: polymorphonuclear infiltrate: 1 female; alveolar epithelium: desquamation: 1 female; alveolar haemorrhage: 1 male, 2 females; increased mitotic activity of parenchymal liver: 2 males, 2 females.Increased instances of dried material around the facial area were detected in all exposure groups,
high dose only: ocular irritation (swollen eyelids, injection of conjunctival blood vessels)
clinical chemistry: males: elevated hematocrit, reduction in MCHC values, depressed clotting time,
histopathology: 2 males, 1 female: increased mitotic activity of parenchymal liverThe observed changes can be explained by an irritative effect of 4 -HBA to the eyes and in the respiratory tract specially in the nose and the lungs and a possible toxic effects on the liver and on the blood.
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