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EC number: 202-705-0 | CAS number: 98-83-9
- 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:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study design comparable to OECD Guideline 413
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 007
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-phenylpropene
- EC Number:
- 202-705-0
- EC Name:
- 2-phenylpropene
- Cas Number:
- 98-83-9
- Molecular formula:
- C9H10
- IUPAC Name:
- (prop-1-en-2-yl)benzene
- Details on test material:
- Lot/batch No.: BNW 13871-4
Purity: 99.5 %
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Male and female F344/N rats were obtained from Taconic Laboratory Animals and Services (Germantown, NY). On receipt, the rats were approximately 4 weeks old. Animals were quarantined for 11 - 12 days and were approximately 6 weeks old on the first day of the studies. Before the studies began, five male and five female rats were randomly selected for parasite evaluation and gross observation for evidence of disease.
Diet
NTP-2000 irradiated pelleted diet, available ad libitum (except during animal exposure and urine collection periods); changed weekly
Water
Tap water via automatic watering system, available ad libitum
Cages
Stainless steel, wire bottom, changed weekly
Cageboard
Untreated paper cage pan liner, changed daily
Chambers
Stainless steel, excreta pan at each of six levels, chambers changed weekly, excreta pans changed daily
Chamber Air Supply Filters
Single HEPA changed annually, charcoal new at study start, Purafil new at study start
Chamber Environment
Temperature: 75 +/- 3 degrees F
Relative humidity: 55 +/- 15 %
Room fluorescent light: 12 hours/day
Air changes: 15 +/- 2/hour
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: clean air
- Details on inhalation exposure:
- Alpha-methylstyrene was held in an 8-gallon stainless steel chemical reservoir. Alpha-methylstyrene was pumped through a pre-heater and into the top of a heated glass column filled with glass beads to increase the surface area for evaporation. Heated nitrogen entering the column from below vaporized the chemical as it conveyed it out of the generator. The vapour was transported to the exposure room at an elevated temperature to prevent condensation. In the distribution manifold cabinet, the vapour was mixed with additional heated air before it entered a short vapour distribution manifold. The pressure in the distribution manifold was fixed to ensure constant flow through the manifold and into the chambers as the flow of vapour to each chamber was adjusted. Electronically actuated metering valves controlled the flow to each chamber. In addition, an exposure-shutoff valve controlled vapour delivery to each chamber. Vapour was diverted to the exposure chamber exhaust until the generation system was stable and exposures were ready to proceed. To start the exposure, the valves were opened to allow the flow of vapour to reach the chamber-metering valves and move into individual temperature-controlled delivery lines to each chamber. The vapour was then injected into the chamber inlet duct where it was diluted with conditioned chamber air to achieve the desired exposure concentration. The study laboratory designed the inhalation exposure chamber so that uniform vapour concentrations could be maintained throughout the chamber with the catch pans in place. The total active mixing volume of each chamber was 1.7 m3. A condensation particle counter was used to count the particles in all chambers before and during generation. No particle counts greater than 200 particles/cm3 were detected.
The alpha-methylstyrene concentrations in the exposure chambers were monitored by an online GC. Samples were drawn from each exposure chamber approximately every 20 minutes during each 6-hour exposure period using a 16-port stream select valve. The online GC was checked throughout the day for instrument drift against an online standard of alpha-methylstyrene in nitrogen supplied by a diffusion standard generator. The online GC was calibrated monthly by a comparison of chamber concentration data to data from grab samples, which were collected with graphitized carbon black sampling tubes, extracted with toluene containing butylbenzene as an internal standard, and analyzed by an offline GC. The volumes of gas were sampled from each chamber at a constant flow rate ensured by a calibrated critical orifice. The offline GC was calibrated with gravimetrically prepared standard solutions of alpha-methylstyrene containing butylbenzene as an internal standard in toluene.
Build-up and decay rates for chamber vapour concentrations were determined with and without animals present in the chambers. At a chamber airflow rate of 15 air changes per hour, the theoretical value for the time to achieve 90 % of the target concentration after the beginning of vapour generation (T90) and the time for the chamber concentration to decay to 10 % of the target concentration after vapour generation was terminated (T10) was approximately 12.5 minutes. Based on experimental data, a T90 value of 12 minutes was selected for the studies. The uniformity of alpha-methylstyrene vapour concentration in the inhalation exposure chambers without animals was evaluated before each of the studies began; concentration uniformity with animals present in the chambers was also measured once during the 3-month studies. The vapour concentration was measured using an online GC. Chamber concentration uniformity was maintained throughout the studies. The persistence of alpha-methylstyrene in the chamber after vapour delivery ended was determined by monitoring the concentration with animals present in the 1000 ppm chambers in the 3-month studies. In the 3-month studies, the concentration decreased to 1 % of the target concentration within approximately 46 minutes in both 1000 ppm chambers. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of alpha-methylstyrene were collected, with and without animals present, from the distribution line, 75 and 1000 ppm exposure chambers, generator reservoir, and vapour trap and analyzed by GC. No evidence of degradation was detected, and no impurities were detected that were not present in the bulk material. HPLC was used to determine the concentration of 4-tert-butyl catechol in exposure chambers; none was detected. Polymer concentration was determined using UV/Vis; the concentration was less than 10 ppm. These results indicated that alpha-methylstyrene was stable for up to 7 weeks in the generator reservoir.
- Duration of treatment / exposure:
- 14 weeks
- Frequency of treatment:
- 6 hours plus T90 (12 minutes) per day on 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
nominal: 0, 75, 150, 300, 600 or 1000 ppm; analytical: 0, 75 +/-2. 150 +/- 3, 300 +/- 7, 603 +/- 11 or 1002 +/- 30 ppm
Basis:
- No. of animals per sex per dose:
- 10 m / 10 f
Additional clinical pathology groups of 10 male and 10 female rats were exposed to the same concentrations for 23 days. One additional exposure day was scheduled during the last exposure week to give male rats at least two consecutive days of exposure before terminal sacrifice. - Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- All animals were observed twice daily. Clinical findings were recorded weekly. Animals were weighed initially, weekly, and at the end of the studies.
Clinical Pathology
Blood was collected from the retroorbital sinus of mice at the end of the study for haematology.
Haematology: haematocrit; packed red cell volume; haemoglobin; erythrocyte, reticulocyte, and platelet counts; Howell-Jolly bodies; mean cell volume; mean cell haemoglobin; mean cell haemoglobin concentration; and leukocyte counts and differentials.
Clinical chemistry: urea nitrogen, creatinine, total protein, albumin, globulin, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and total bile acids
Urinalysis: creatinine, glucose, protein, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase, N-acetyl-beta-D-glucosaminidase, volume, and specific gravity
Blood was collected from the retroorbital sinus of clinical pathology rats on days 3 and 23 and from core study rats at the end of the study for haematology and clinical chemistry analyses.
After three (males) or four (females) consecutive exposure days during week 12, core study rats were placed in metabolism cages, and urine was collected over ice for 16 hours. During collection, the animals had access to water but not to food. After collection, the appearance, volume, and specific gravity of the samples were determined and recorded. A microscopic analysis of the urinary sediment was then performed. - Sacrifice and pathology:
- Necropsies were performed on all core study animals. Organs weighed were heart, right kidney, liver, lungs, right testis, and thymus.
Histopathology
Complete histopathology was performed on all core study chamber control and 1000 ppm mice. In addition to gross lesions and tissue masses, the following tissues were examined to the no-effect level: adrenal gland, bone with marrow, brain, clitoral gland, oesophagus, eyes, gallbladder, harderian gland, heart and aorta, large intestine (caecum, colon, rectum), small intestine (duodenum, jejunum, ileum), kidney, larynx, liver, lung (with mainstem bronchus), lymph nodes (mandibular, mesenteric, bronchial, mediastinal), mammary gland, nose, ovary, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skin, spleen, stomach (forestomach and glandular), testis (with epididymis and seminal vesicle), thymus, thyroid gland, trachea, urinary bladder, and uterus.
The left kidney was removed from all male and female core study rats at terminal necropsy, sectioned in half longitudinally, placed in a cassette, and fixed with 10 % neutral buffered formalin for approximately 24 hours. After fixation, one half of the left kidney was processed and embedded in paraffin. Analysis of alpha2u-globulin in supernatants prepared from kidney homogenates was conducted using a competitive indirect enzyme-linked immunosorbent assay (ELISA). The amount of alpha2u-globulin was measured by comparing the relative fluorescent signal intensity in the study samples to that observed with known amounts of alpha2u-globulin present in calibration standards. Calibration standards and ELISA control standards (negative and positive) were plated in predetermined wells on 96-well microtiter plates. Calibration standards and study samples were assayed in triplicate. - Other examinations:
- Sperm Motility and Vaginal Cytology
Epididymal sperm concentration and motility; spermatid heads/testis; and left cauda, epididymis, and testis weights were evaluated in males from the 0, 300, 600, and 1000 ppm exposure groups at terminal sacrifice. For 12 consecutive days prior to scheduled terminal sacrifice, vaginal cytology slides were prepared for all surviving females in the 0, 300, 600, and 1,000 ppm exposure groups. Relative numbers of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were determined and used to ascertain oestrous cycle stage (i.e., dioestrus, prooestrus, oestrus, and metoestrus).
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:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- 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:
- no effects observed
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 300 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Kidney & liver
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- From this study a NOAEL of 300 ppm for rats was derived.
- Executive summary:
In this study (design comparable to OECD Guideline 413), groups of 10 male and 10 female rats were exposed by whole-body inhalation to alpha-methylstyrene at concentrations of 0, 75, 150, 300, 600 or 1000 ppm for 6 hrs per day and 5 days per week for 14 weeks. Additional clinical pathology groups of 10 male and 10 female rats were exposed to the same concentrations for 23 days. All rats survived to the end of the study, and mean body weights of all exposed groups were similar to those of the chamber controls. Kidney weights were significantly increased in 1000 ppm males and at >= 600 ppm females. Statistically significant increases in liver weights occurred at >= 150 ppm males and at >= 600 ppm females. The incidences of renal hyaline droplet accumulation were similar between exposed groups and chamber control groups, but the severity of hyaline droplet accumulation in >= 600 ppm males was greater than in chamber controls. Consistent with the hyaline droplet accumulation, an exposure related increase in alpha2u-globulin was detected in the kidneys of males exposed to alpha-methylstyrene. Morphologic changes were not detected in the liver.
The effects observed in male rats at concentrations of 300 and below are not considered to be relevant for human health and a the relevant NOAEL of 300 ppm has been derived.
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