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EC number: 701-175-2 | CAS number: -
- 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:
- Experimental study period: 25-5-1993 to 22-06-1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Amines, C10-C14-tert-alkyl
- EC Number:
- 701-175-2
- Cas Number:
- 68955-53-3
- Molecular formula:
- C10H23N to C14H31N
- IUPAC Name:
- Amines, C10-C14-tert-alkyl
Constituent 1
- Specific details on test material used for the study:
- Test material identified as TAPA, TD 93-030, Lot 5-0027-93
Pale straw coloured liquid
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York, USA
- Age at study initiation: 21-23 days, at receipet
- Weight at study initiation: 50-75 g, at receipt
- Fasting period before study: not reported
- Housing: suspended wire mesh cage
- Diet (e.g. ad libitum): Purina certified rodent chow 5002; withheld during exposure
- Water (e.g. ad libitum): ad libitum; withheld during exposure
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.1 - 23.4 degrees C
- Humidity (%): 67.8 - 74.6%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark
IN-LIFE DATES: From: May 25, 1993 To: June 22, 1993
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: not applicable- vapor study
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 1250 L stainless steel, glass and Plexiglass chambers
- Method of holding animals in test chamber: PVC nose-only restraining tubes
- Source and rate of air: Compressed air at 0.25 to 32 L/min
- Method of conditioning air: no data
- System of generating particulates/aerosols: study conducted with vapor, not aerosol
- Temperature, humidity, pressure in air chamber: 23.1-23.4 degrees C; 67.8 - 74.6%; pressure not reported
- Air flow rate: air flow rate adjutsted to 99% of the maximum vapor concentration
- Air change rate: no reported
- Method of particle size determination: study conducted with vapor, not aerosol
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: an impinger located outside each chamber containing 8-12 mL of propylene glycol placed in an ice bath
- Samples taken from breathing zone: yes
VEHICLE (if applicable) no vehicle - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- In order to determine the analytical concentration of the tetst material in the chambers, one impinger located outside wach chamber was used for sampling. The impingers contained 8-12 mL of propylene glycol and were placed in an ice bath. The amount of propylene glycol placed in the impingers was based on the amount of test material (mg) being collected over a 6-hour exposure. The air control chamber was sampled weekly to validate the lack of test material in the control atmosphere.
After collecting a sample with the impingers, the collecting solution was quantitatively transferred to pre-weighted 20 mL scintillation vials and weighed again to determine the total material present. The solution was then sent for gas chromatographic analysis. - Duration of treatment / exposure:
- 6 hrs/day
- Frequency of treatment:
- 5 days/week for 4 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2, 19, 129, 537 mg/m3
Basis:
analytical conc.
- No. of animals per sex per dose:
- 10
In addition, 2 males and 2 females were assigned to each group as health monitoring sentinels - Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: not reported
- Rationale for animal assignment (if not random): computer randomization
- Rationale for selecting satellite groups: not applicable
- Post-exposure recovery period in satellite groups: not applicable
- Section schedule rationale (if not random): not reported - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Signs of intoxication, mortality, morbidity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined : Yes weekly
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: on the day of necropsy
- Anaesthetic used for blood collection: Yes (identity) Nembutal
- Animals fasted: Yes ; overnight
- How many animals: all surviving animals
- Parameters checked
hematocrit
hemoglobin
red blood cell
white blood cell count
platelet count
mean cell corpuscular volume
mean cell corpuscular hemoglobin
mean corpuscular hemoglobin conc.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day of necropsy
- Animals fasted: Yes
- How many animals: all surviving animals
- Parameters checked
triglyceride
cholesterol
blood urea nitrogen
glucose
alkaline phosphatase
total protein
albumin
chloride
sodium
potassium
globulin
albumin:globulin ratio
creatinine
bilirubin (total)
calcium
inorganic phosphorous
glutamic pyruvic transaminase/alanine aminotransferase activity
glutamic oxaloacetic transaminase/asparate aminotransferase activity
gamma-glutamyl transferase activity
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to the first day of exposure, and shortly after animals were removed from the chambers on the last day of exposure.
- Dose groups that were examined: all animals prior to exposure; all surviving animals on the last day of exposure
- Battery of functions tested: sensory activity / grip strength / motor activity / other: convulsions, tremors, stereotypic or bizzarre behavior
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- Macroscopic: Gross examination included examination of the external surface of the body, all orifices and the cranial, thoracic, and abdominal cavities and their contents.
HISTOPATHOLOGY: Yes
- Microscopic: Tissues processed and examined microscopically will be collected, saved, weighed and fixed in 10% neutral buffered formalin. Tissues included but not limited to, the nasal cavity, liver, brain, kidney, spinal cord (cervical, thoracic, lumbar), sciatic nerve, skeletal muscle, adrenals, spleen, trachea, larynx, heart, and gross lesions. - Other examinations:
- Neurologic evaluations were performed the day prior to the first day of exposure, and shortly after animals were removed from the chambers on the last day of exposure.
- Statistics:
- One-way analysis of covariance models were used to assess the presence or absence of an overall compound effect. Separate one-way analyses were used within the male and female data to assess overall treatment group effects. Pairwise comparisons of least square means between control and each treatment level were evaluated using Dunnett's t-test. The criterion for statistical significance for all comparisons was p-value of 0.05 or less.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- All animals receiving 537 mg/m3 died by exposure Day 11, prior to death these animals exhibited treatment-related labored breathing, respiratory noise, gasping, unstable gait, tremors, salivation and lacrimation.
At 129 mg/m3 transient occurences of unstable gait, respiratory noise, salivation and lacrimation were observed.
Animals exposed at 19 mg/m3 showed a single incidence of lacrimation, this was judged not to be treatment related.
No treatment related signs were observed at 2 mg/m3. Red stained fur around eyes and muzzle and frequent struggling in the nose-only restraint tubes were observed throughout the study in all test material exposed groups. A single death in group 1 (Control) was attributable to over restraint in the nose only tube. - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- All animals receiving 537 mg/m3 died by exposure Day 11, prior to death these animals exhibited treatment-related labored breathing, respiratory noise, gasping, unstable gait, tremors, salivation and lacrimation.
A single death in group 1 (Control) was attributable to over restraint in the nose only tube. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant bodyweight decreases occured in the 537 mg/m3 males during week 1 and in females during Week 1 and 2. Males exposed to 129 mg/m3 showed statistically significant decreases in bodyweight and bodyweight change during Weeks 2, 3 and 4. The females exposed at 129 mg.m3 showed statistically significant decreases in bodyweight and bodyweight changes during Weeks 3 and 4. At 19 mg/m3 statistically significant decreases in bodyweight and bodyweight change were seen in females during Week 2. No other bodyweight effects were observed in this group.Females in the 2 mg/m3 exposure group showed statistically significant decreases in bodyweight and bodyweight change during Weeks 2, 3 and 4. No other bodyweight effects were observed in this group.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- A statistically significant decrease in feed consumption for the 537 mg/m3 in both sexes was observed during Week 1. A statistically significant decrease i nthe feed consumption for the 129 mg/m3 males was observed during Weeks 2 and 3. No other feed consumption effects were seen i nany other group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Animals exposed at 19 mg/M3 showed statistically significant increase in platelets for the males and statistically significant decrease in mean cell hemoglobin and mean cell hemoglobin concentrations for the females. No changes in hematology parameters were seen at any other concentration. In the absence of a concentration-response relationship, none of the above changes were judged to be treatment-related.
No exposure related differences in white blood cell differential parameters were observed. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Statistically significant decreases were observed in total protein and globulin in males at 129 mg/M3. At 19 mg/M3 statistically significant decreases were observed in glutamic oxaloacetic transaminase, glutamic pyruvic transaminase in males and triglyceride in females. Males exposed at 2 mg/M3 showed a statistically significant decrease in creatinine and glutamic oxaloacetic transaminase; females in this group showed an increase in glutamic oxaloacetic transaminase. In the absence of a concentration-response relationship, none of the above changes were judged to be exposure-related.
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The organ weight data showed a statistcally significant increase in the absolute lung weight of the 2 mg/m3 males. No other changes in organ weights were seen in any other group. In the absence of a lung weight effect at higher concentrations, this finding was judgen not to be treatment related.
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The nasal cavity, in particular both respiratory and olfactory epithelium, was the most sensitive target organ.
All animals exposed to 537 mg/M3 died during the study, and at the time of necropsy many animals were observed with distended stomachs.
Difficulty in flushing formalin through the nasopharyngeal duct was noted in many of these animals at the time of necropsy. No exposure-related gross observations were noted on surviving animals.
Microscopic examination of male and female rats exposed to 537 mg/M3 showed changes in the nasal cavity, larynx, trachea, and lung. The nasal cavity changes were moderate to severe desquamation of the respiratory and olfactory epithelium, epithial necrosis and inflammation of the submucosa. In addition, all meati and primarily the dorsal meati had exudate composed of mucous, fibrin, erythrocytes, exfoliated epithelium and inflammatory cells. The larynx and trachea had epithelial necrosis, submucosal inflammation and exudate in their lumens. Two female rats had foci of inflammation of bronchi, bronchioles and/or alveoli. Specific examination of tissues from the central (brain and spinal cord) and peripheral (sciatic nerve) nervous systems as well as skeletal muscle from animals exposed to 537 mg/M3 revealed no changes
indicative of neurotoxicity.
The nasal cavity was the only target tissue in animals exposed to 129 mg/M3 of the test material. The lesions were primary graded as slight and focal in nature. These lesions consisted of necrosis of respiratory and olfactory epithelium accompanied by inflammation in the mucosa and submucosa, as well as, exudate in meati which usually was overlying necrotic foci. Also observed were foci of respiratory epithelial hyperplasia and squamous metaplasia (respiratory epithelium replaced by squamous epithelium). The olfactory epithelium and underlying Bowman's gland epithelium were atrophied. In the absence of any nervous system lesions at 537 mg/M3, no examination of skeletal muscle or tissues from the central and peripheral nervous systems were performed in the other exposed groups. Rats exposed to 19 or 2 mg/M3 of the test material had no exposure-related microscopic changes. - Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- Time of death: all animals exposed to 537 mg/m3 died by exposure day 11; 1 during week 2 of dosing - Number of deaths at each dose: 10 at 537 mg/m3; 1 accidental death in control group; all animals exposed to 537 mg/m3 died by exposure day 11 and one control animal died during week 2 of exposure.
- Clinical signs: Animals exposed to 537 mg/m3 prior to death exhibited treatment-related labored breathing, respiratory noise, gasping, unstable gait, tremors, salivation, and lacrimation. At 129 mg/m3 transient occurrences of unstable gait, respiratory noise, salivation, and lacrimation were observed. Animals exposed at 19 and 2 mg/m3 showed no treatment-related signs of toxicity.
BODY WEIGHT AND WEIGHT GAIN
Statistically significant decreases in body weight occurred in 537 mg/m3 males during week 1, and in females during weeks 1 and 2. Males exposed to 129 mg/m3 showed statistically significant decreases in body weight and body weight change during weeks 2, 3, 4. The females exposed at 129 mg/m3 showed statistically significant decreases in body weight and body weight change during weeks 3 and 4. At 19 mg/m3 statistically significant decreases in body weight and body weight change were seen in the females during week 2. Females in the 2 mg/m3 exposure group showed statistically significant decreases in body weight and body weight change during weeks 2, 3, and 4.
FOOD CONSUMPTION
A statistically significant decrease in feed consumption was observed in all animals in the 537 mg/m3 exposure groups during week 1. A statistically significant decrease in the feed consumption for the 129 mg/m3 males was observed during weeks 2 and 3.
FOOD EFFICIENCY not examined
WATER CONSUMPTION not examined
OPHTHALMOSCOPIC EXAMINATION not examined
HAEMATOLOGY
No treatment-related effect on any hematologic parameter at any dose level. Animals exposed at 19 mg/m3 showed statistically significant decrease in mean cell hemoglobin and mean cell hemoglobin concentrations for the females. No changes in hematology parameters were seen at any other concentration. In the absence of a dose-response relationship, none of the above changes were judged treatment-related. No exposure-related differences in differential parameters were observed.
CLINICAL CHEMISTRY
- Clinical chemistry: No treatment-related clinical chemistry effects were observed in any group. Statistically significant decreases in total protein and globulin in males at 129 mg/m3. At 19 mg/m3 statistically significant decreases in glutamic oxaloacetic transaminase, glutamic pyruvic transaminase in males and triglyceride in females. Males exposed at 2 mg/m3 showed a statistically significant decrease in creatinine and glutamic oxaloacetic transaminase; females in this group showed an increase in glutamic oxaloacetic transaminase. In the absence of a concentration-response relationship, none of the above changes were judged to be treatment-related.
URINALYSIS not examined
NEUROBEHAVIOUR
ORGAN WEIGHTS
No treatment-related organ weight changes observed at any dose level.
GROSS PATHOLOGY
Gross pathologic changes were observed only in animals exposed to 537 mg/m3. These changes consisted of partially or fully blocked nasal cavities and gas-filled stomachs.
HISTOPATHOLOGY: NON-NEOPLASTIC
Microscopic examination of male and female rats exposed to 537 mg/m3 showed changes in the nasal cavity, larynx, trachea, and lung. The nasal cavity changes were moderate to severe desquamation of the respiratory and olfactory epithelium, epithial ncerosis and inflammation of the submucosa. In addition, all meati and primarily the dorsal meati had exudates composed of mucous, fibrin, erythrocytes, exfoliated epithelium and inflammatory cells. The larynx and trachea had epithelial necrosis, submucosal inflammation an exudates in their lumens. Two female rats had foci of inflammation of bronchi, bronchioles and/or alveoli. Specific examination of tissues from the central (brain and spinal cord) and peripheral (sciatic nerve) nervous system as well as skeletal muscle from animals exposed to 537 mg/m3 revealed no changes indicative of neurotoxicity. The nasal cavity was the only target tissue in animals exposed to 129 mg/m3. The lesions were primary graded as slight and focal in nature. These lesions consisted of necrosis of respiratory and olfactory epithelium accompanied by inflammation in the mucosa and submucosa, as well as, exudates in meati which usually was overlying necrotic foci. Also observed were foci of respiratory epithelial hyperplasia and squamosus metaplasia (respiratory epithelium replaced by squamous epithelium). The olfactory epithelium and underlying Bowman's gland epithelium were atrophied. Rats exposed to 19 and 2 mg/m3 had not exposure-related microscopic changes.
HISTOPATHOLOGY: NEOPLASTIC (if applicable) not applicable
OTHER: The sentinel animal serology results were negative for the presence of adventitious virus and bacteria antibodies.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 19 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: overall effects histopathology of the nasal cavities
- Dose descriptor:
- BMCL10
- Effect level:
- 36.2 mg/m³ air
- Sex:
- male/female
- Basis for effect level:
- other: BMDL10 based on nasal cavity data, as this was the most sensitive effect (Multistage model)
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Inhalation exposure of the test material produced 100%
mortality at 537 mg/m3. Prior to the death, these animals
exhibited labored breathing, respiratory noise, gasping,
unstable gait, tremors, salivation, lacrimation, and
decresed body weight, body weight gain and feed consumption. At 129 mg/m3, transient occurrences of unstable gait,
respiratory noise, salivation, lacrimation, and slight
decreased body weight gains and feed consumption were
observed.
No treatment-related signs were observed at 19 and 2 mg/m3. Organ weights and blood analysis revealed no treatment-related effects. At the end of the four-week exposure period, neurological evalutions of all surviving animals showed no signs of a cumulative toxic effect on the nervous system in any group. On the basis of the most sensitive indictor of toxicity, the histopathological changes seen in the nasal cavities, the NOEL for a four-week nose-only inhalation exposure of the test material was 19 mg/m3.
The response of 0 0 0 2 10 was the most sensitive therefore the BMD value of 80.96 mg/m3 and the BMDL value of 36.20 mg/m3 are chosen corresponding to the multistage model with the lowest AIC. - Executive summary:
Five groups, designated 1,2,3,4 and 5, each containing 10 male and 10 female Crl:CD BR rats, received nose-only inhalation exposures for 6 hours per day, 5 days a week, for four weeks to air or vapors of the test material. Group 1 animlas were exposed to filtered air only. Groups 2,3,4 and 5 were exposed to 2, 19, 129, and 537 mg/m3 of the test material, respectively. All surviving animals from each group were necropsied at the end of the four week exposure period. Body weight, feed consumption, clinical signs, neurology, clinical chemistry, hematology, organ weight and histopathology evaluations were performed on all surviving animals during this study.
All animlas exposed to 537 mg/m3 died by exposure day 11. Prior ro death these animals exhibited treatment-related labored breathing, respiratory noise, gasping, unstable gait, tremors, salivation and lacrimation. At 129 mg/m3 transient occurrences of unstable gait, respiratory noise, salivation and lacrimation were observed. Animals exposed to 19 mg/m3 showed no treatment related signs of toxicity, with the exception of one incident of lacrimation. No treatment-related signs were observed at 2 mg/m3. At the end of the four-week exposure period, neurological evaluations of all surviving animals showed no effect on the nervous system in any group.
Treatment -related decreases in body weight and feed consumption was observed in both sexes at 537 mg/m3. Animlas exposed to 129 mg/m3 showed a decrease in body weights for both sexes, and a decrease in feed consumption in males. Animlas exposed to 19 and 2 mg/m3 showed no treatment-related changes in body weight or feed consumption.
No treatment-related effects were seen in any group for clinical chemistry, hematology or organ weights.
Gross pathologic changes were observed only in animals exposed to 537 mg/m3. These changes consisted of partially or fully blocked nasal cavities and gas-filled stomachs. Microscopic examination of male and female rats exposed to 537 mg/m3 showed chnages in the nasal cavity, larynx, trachea, and lung. The nasal cavity changes were moderate to severe desquamation of the respiratory and olfactory epithelium, epithelial necrosis and inflammation. The larynx and trachea had epithelial necrosis and inflammation. The lungs of two females showed foci of inflammation in the bronchi, bronchioloes and/or alveoli. Male and female rats exposed to 129 mg/m3 showed slight focal lesions of the nasal cavity. Rats exposed to 19 or 2 mg/m3 had no exposure related nasal cavity microscopic changes.
On the basis of the most sensitive indicator of toxicity, the histopathological changes seen in the nasal cavities, the no observed effect level (NOEL) following four weeks of nose-only inhalation exposure to the test material was 19 mg/m3.
A benchmark dose (BMD) analysis of relevant toxicity data for primene was conducted in order to establish BMD and BMDL (lower limit of the 95% confidence interval on the BMD) values. The U.S. EPA’s Benchmark Dose Software (BMDS) was used for the analysis (U.S. EPA 2009). Data from a four week vapor inhalation study in rats was used (Hagan et al., 1994). The exposure doses were 0, 2, 19, 129, and 537 mg/cubic meter of primene.
The key endpoints evaluated were body weight at week four (dose 537 not used due to deaths before the end of the study) and the nasal cavity with both the respiratory and olfactory epithelium. The study report indicated the nasal cavity was the most sensitive target organ with histopathologic changes, particularly desquamation, necrosis and inflammation.
The results for models for a particular response were all within a factor of 3 so the model with the lowest AIC is the most desirable. The plots show that the fits for the models for incidence 0 0 0 2 10 were all very similar except the quantal linear model which had a poorer fit than the others. The response of 0 0 0 2 10 was the most sensitive therefore the BMD value of 80.96 mg/m3 and the BMDL value of 36.20 mg/m3 are chosen corresponding to the multistage model with the lowest AIC.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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