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EC number: 211-105-8 | CAS number: 629-73-2
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1982-12-21 to 1983-04-22
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study is classified as reliable without restrictions because it was conducted according to OECD 413 guidelines and was GLP compliant.
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1982-12-21 to 1983-04-22
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study is classified as reliable without restrictions because it was conducted according to OECD 413 guidelines and was GLP compliant.
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- Only a few major organs were examined histologically.
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc.
- Fasting period before study: No
- Housing: Individually
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 19 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light
IN-LIFE DATES: From: 1983-01-07 To: 1983-04-22 - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: None
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:7700 Litre King-Lar stainless steel/glass chambers housed in inhalation suites
- Method of holding animals in test chamber: None
- Source and rate of air: Main air supply line at an unspecified rate
- System of generating particulates/aerosols: A head space sweep technique using dry nitrogen through a mass flow controller into a stainless steel container supplied with a continuous feed of test material, then introduced into the main air supply line with a static mixing device, then fed into the exposure chamber
- Temperature, humidity, pressure in air chamber: 22 to 26 degrees Celsius and 30 to 63% humidity
- Air flow rate: 533 cubic meters to 578 cubic meters
- Air change rate: 1.3 to 1.6 cubic meters per minute
TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of hex-1-ene was determined by gas chromatography using an 80/100 mesh Carbopak® column with 0.19% picric acid and flame ionization detection. Vapour concentration was determined about every ten minutes during exposure. Samples were taken near the centre of the chamber where the animals were positioned in the exposure chamber. Three Varian Vista Series 4600 Gas Chromatographs, calibrations performed daily, with one CDS 401 Chromatography Data System was used for the concentration analyses.
- Samples taken from breathing zone: Yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical concentrations for the low, middle, and high exposures ranged from 297 to 300 parts per million, 990 to 1002 parts per million, and 2958 to 3000 parts per million, respectively. The analytical concentrations were slightly (<10%) lower than the calculated nominal concentrations.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours a day, 5 days a week
- Remarks:
- Doses / Concentrations:
300, 1000, or 3000 parts per million
Basis:
analytical conc. - No. of animals per sex per dose:
- Forty animals/sex/dose; ten animals/sex/dose for neuromuscular testing, ten animals/sex/dose for interim sacrifice at 7 weeks, and twenty animals/sex/dose for terminal sacrifice
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Based on an 11-day study (WRC-TIR-733)
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes, mortality and clinical signs
- Time schedule: Before and after exposure and once on days with no exposure
DETAILED CLINICAL OBSERVATIONS: No data reported.
BODY WEIGHT: Yes
- Time schedule for examinations: Pretreatment and weekly during exposure
FOOD CONSUMPTION: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Pretest, week 7 and week 13
- Anaesthetic used for blood collection: No data reported
- Animals fasted: Yes
- How many animals: Ten animals per sex and dose at study initiation, ten animals per sex and dose at 7 weeks, and twenty animals per sex and dose at week 13
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Pretest, week 7, and week 13
- Animals fasted: Yes
- How many animals: Ten animals per sex and dose at study initiation, ten animals per sex and dose at 7 weeks, and twenty animals per sex and dose at week 13
- Parameters checked in table 2 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Weeks 7 and 13
- Metabolism cages used for collection of urine: No data reported.
- Animals fasted: Yes
- Parameters checked in table 3 were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Pretest and weekly during exposure
- Dose groups that were examined: All groups
- Battery of functions tested: Balance and neuromuscular coordination
OTHER: Sperm counts - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 4) - Other examinations:
- The lungs, liver, kidney, brain, heart, spleen, and right testicle or uterus were weighed. Sperm counts, measured with a hemocytometer and phase-contrast microscope, were performed using the left testicle of each male rat after detunication, weighing, and homogenization.
- Statistics:
- Body weight differences were analyzed by analysis of covariance using initial weights of individual rats on day -2 as a covariate with the least squares difference test. Organ weight, clinical chemistry, haematology, urinalysis, and organ to body weight ratio data were analyzed by Dunnett’s t-test on the ranked data. Neuromuscular coordination data were adjusted by summing the time for the best 3 of 4 trials for each rat and analyzed by analysis of variance or analysis of covariance. All statistics were measured with p<0.05.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No deaths occurred. There were no clinical signs related to treatment.
BODY WEIGHT AND WEIGHT GAIN: Decreased body weight was observed in 3000-ppm females (statistically significant) and males (statistically significant only sporadically). The reported 4% reduction in body weight, while statistically significant, is of limited toxicological significance. (Table 5)
HAEMATOLOGY: There were no treatment-related findings at interim sacrifice. At terminal sacrifice, 1000-ppm females and 3000-ppm males and females had higher haematocrit and red blood cells, and in 1000-ppm and 3000-ppm females mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were lower. Although these findings appear treatment-related, they were not associated with any histopathology findings, results are not dose related, and changes were within 5% of the control. (Table 6)
CLINICAL CHEMISTRY: There was an increase in phosphorus in males at all treatment concentrations, which may be due to a low level in the control. There was a consistent increase in phosphorus in 1000-ppm and 3000-ppm females at interim and terminal sacrifice (Table 7). The toxicological significance of this finding is doubtful.
URINALYSIS: There were no treatment-related changes.
NEUROBEHAVIOUR: There were no treatment-related effects.
ORGAN WEIGHTS: There was a slight (5% or less) but significant decrease in absolute and relative testes weight in 3000-ppm males that was not associated with any change in sperm parameters or histopathology. This decrease, while statistically significant, is of limited toxicological relevance. Other changes in organ weights were related to the reduced body weight.
GROSS PATHOLOGY: There were no treatment-related findings.
HISTOPATHOLOGY: NON-NEOPLASTIC: There were no treatment-related findings.
HISTOPATHOLOGY: NEOPLASTIC (if applicable): There were no treatment-related findings.
OTHER FINDINGS: There were no treatment-related changes in sperm counts. - Dose descriptor:
- NOAEC
- Effect level:
- 3 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 10,326 mg/m3; no toxicologically relevant findings at the highest concentration tested.
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEC for this study was 3000 ppm (10,326 mg/m3) based on a lack of toxicologically relevant findings at the highest concentration tested.
- Executive summary:
In a 90-day inhalation toxicity study, Neodene 6 alpha olefin was administered to forty Fischer 344 rats/sex/concentration by dynamic whole body exposure at concentrations of 0, 300, 1000, or 3000 parts per million (corresponding to 0; 1033; 3442; or 10, 326 mg/m3) for 6 hours a day, 5 days a week, for 13 weeks. Ten of the animals/sex/concentration were used for neuromuscular testing, ten of the animals/sex/concentration were sacrificed after 7 weeks of exposure, and twenty animals/sex/concentration were sacrificed after 13 weeks of exposure.
Subchronic inhalation of Neodene 6 alpha olefin for 13 weeks did not produce any adverse respiratory, neuromuscular, or testicular effects in rats. Decreased body weight was observed in 3000 -ppm females (statistically significant) and males (statistically significant only sporadically). Decreased absolute liver and kidney weights were observed in 3000-ppm females; however, these findings were considered secondary to reduced body weight in the absence of histopathological findings in these organs. There were statistically significant differences in haematology and clinical chemistry values, but the changes were slight (generally within 5% of the control), were not dose related, and/or not associated with any histopathology findings.Increased phosphorus levels were reported in males at all treatment levels and females exposed to 1000 and 3000 ppm hex-1-ene. The toxicological significance of these findings is doubtful. The NOAEC is 3000 parts per million (10,326 mg/m3) based on a lack of toxicologically relevant findings at the highest concentration tested.
Table 5. Body weight data
Body weight data expressed in grams (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Day 0 |
161.28 ± 2.61 n=40 |
159.84 ± 2.58 n=40 |
159.72 ± 2.93 n=40 |
161.58 ± 2.37 n=40 |
Day 33 |
250.1 ± 3.9 n=40 |
252.3 ± 3.1 n=40 |
246.2 ± 4.4 n=40 |
245.0 ± 3.2 n=40 |
Day 61 |
305.2 ± 4.3 n=30 |
305.2 ± 3.8 n=30 |
302.3 ± 5.3 n=30 |
295.1 ± 3.7 n=30 |
Day 89 |
338.9 ± 4.2 n=30 |
340.8 ± 4.0 n=30 |
339.7 ± 5.2 n=30 |
329.0 ± 3.6 n=30 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Day 0 |
126.04 ± 1.29 n=40 |
125.30 ± 1.28 n=40 |
125.69 ± 1.28 n=40 |
125.94 ± 1.31 n=40 |
Day 33 |
164.44 ± 1.90 n=40 |
162.93 ± 1.36 n=40 |
163.82 ± 1.47 n=40 |
160.18 ± 1.48 n=40 |
Day 61 |
183.80 ± 2.47 n=30 |
181.83 ± 1.61 n=30 |
181.23 ± 1.73 n=30 |
175.41 ± 1.75 * n=30 |
Day 89 |
194.87 ± 2.62 n=30 |
194.62 ± 1.68 n=30 |
192.93 ± 2.02 n=30 |
187.08 ± 1.85 * n=30 |
Table 6. Selected Hematological Data
Hematological Data (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Haematocrit (%) (week 13) |
44.4 ± 0.5 n=20 |
43.7 ± 0.7 n=20 |
45.0 ± 0.1 n=20 |
45.3 ± 0.3* n=20 |
RBC (106/ mm3) (week 13) |
6.58 ± 0.07 n=20 |
6.49 ± 0.12 n=20 |
6.65 ± 0.03 n=20 |
6.71 ± 0.05 * n=20 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Haematocrit (%) (week 13) |
40.9 ± 0.3 n=20 |
42.5 ± 0.7 n=20 |
43.1 ± 0.8 * n=20 |
42.6 ± 0.05 * n=20 |
RBC (106/ mm3) (week 13) |
5.78 ± 0.05 n=20 |
6.01 ± 0.10 n=20 |
6.09 ± 0.11 * n=20 |
6.04 ± 0.07 * n=20 |
*Statistically significant at p<0.05
Table 7. Phosphorus levels in the blood
Clinical Chemistry Data (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Phosphorus mg/dL (week 7) |
6.98 ± 0.23 n=10 |
7.21 ± 0.26 n=10 |
8.18 ± 0.29 * n=10 |
7.52 ± 0.23 n=10 |
Phosphorus mg/dL (week 13) |
6.42 ± 0.15 n=20 |
7.27 ± 0.20 * n=20 |
7.22 ± 0.14 * n=20 |
7.72 ± 0.34 * n=20 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Phosphorus mg/dL (week 7) |
6.28 ± 0.57 n=10 |
6.39 ± 0.42 n=10 |
7.59 ± 0.37 * n=10 |
7.78 ± 0.27 * n=10 |
Phosphorus mg/dL (week 13) |
5.64 ± 0.19 n=20 |
6.07 ± 0.24 n=20 |
6.46 ± 0.24 * n=20 |
6.85 ± 0.15 * n=20 |
*Statistically significant at p<0.05.
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 984
- Report date:
- 1984
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- Only a few major organs were examined histologically.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Hex-1-ene
- EC Number:
- 209-753-1
- EC Name:
- Hex-1-ene
- Cas Number:
- 592-41-6
- Molecular formula:
- C6H12
- IUPAC Name:
- hex-1-ene
- Details on test material:
- - Name of test material (as cited in study report): Neodene 6 alpha olefin
- Substance type: C6 alpha olefin
- Physical state: Liquid
- Analytical purity: Not reported in study report, but published information states 97.2% 1-hexene
- Impurities (identity and concentrations): 1.1% trans-2-hexene, 0.6% cis-2-hexene, 0.5% cis and trans-3-hexene, and 0.6% 2-ethyl-1-butene
- Lot/batch No.: Stated as assigned WRC Tox sample No. 571D
- Stability under test conditions: Stable
- Storage condition of test material: Under nitrogen at room temperature
- Other: The characterization and stability were stated to be described in Analytical RIR 343, which was not provided in the study report.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc.
- Fasting period before study: No
- Housing: Individually
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 19 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light
IN-LIFE DATES: From: 1983-01-07 To: 1983-04-22
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: None
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:7700 Litre King-Lar stainless steel/glass chambers housed in inhalation suites
- Method of holding animals in test chamber: None
- Source and rate of air: Main air supply line at an unspecified rate
- System of generating particulates/aerosols: A head space sweep technique using dry nitrogen through a mass flow controller into a stainless steel container supplied with a continuous feed of test material, then introduced into the main air supply line with a static mixing device, then fed into the exposure chamber
- Temperature, humidity, pressure in air chamber: 22 to 26 degrees Celsius and 30 to 63% humidity
- Air flow rate: 533 cubic meters to 578 cubic meters
- Air change rate: 1.3 to 1.6 cubic meters per minute
TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of hex-1-ene was determined by gas chromatography using an 80/100 mesh Carbopak® column with 0.19% picric acid and flame ionization detection. Vapour concentration was determined about every ten minutes during exposure. Samples were taken near the centre of the chamber where the animals were positioned in the exposure chamber. Three Varian Vista Series 4600 Gas Chromatographs, calibrations performed daily, with one CDS 401 Chromatography Data System was used for the concentration analyses.
- Samples taken from breathing zone: Yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical concentrations for the low, middle, and high exposures ranged from 297 to 300 parts per million, 990 to 1002 parts per million, and 2958 to 3000 parts per million, respectively. The analytical concentrations were slightly (<10%) lower than the calculated nominal concentrations.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours a day, 5 days a week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
300, 1000, or 3000 parts per million
Basis:
analytical conc.
- No. of animals per sex per dose:
- Forty animals/sex/dose; ten animals/sex/dose for neuromuscular testing, ten animals/sex/dose for interim sacrifice at 7 weeks, and twenty animals/sex/dose for terminal sacrifice
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: Based on an 11-day study (WRC-TIR-733)
- Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes, mortality and clinical signs
- Time schedule: Before and after exposure and once on days with no exposure
DETAILED CLINICAL OBSERVATIONS: No data reported.
BODY WEIGHT: Yes
- Time schedule for examinations: Pretreatment and weekly during exposure
FOOD CONSUMPTION: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Pretest, week 7 and week 13
- Anaesthetic used for blood collection: No data reported
- Animals fasted: Yes
- How many animals: Ten animals per sex and dose at study initiation, ten animals per sex and dose at 7 weeks, and twenty animals per sex and dose at week 13
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Pretest, week 7, and week 13
- Animals fasted: Yes
- How many animals: Ten animals per sex and dose at study initiation, ten animals per sex and dose at 7 weeks, and twenty animals per sex and dose at week 13
- Parameters checked in table 2 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Weeks 7 and 13
- Metabolism cages used for collection of urine: No data reported.
- Animals fasted: Yes
- Parameters checked in table 3 were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Pretest and weekly during exposure
- Dose groups that were examined: All groups
- Battery of functions tested: Balance and neuromuscular coordination
OTHER: Sperm counts - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (see table 4) - Other examinations:
- The lungs, liver, kidney, brain, heart, spleen, and right testicle or uterus were weighed. Sperm counts, measured with a hemocytometer and phase-contrast microscope, were performed using the left testicle of each male rat after detunication, weighing, and homogenization.
- Statistics:
- Body weight differences were analyzed by analysis of covariance using initial weights of individual rats on day -2 as a covariate with the least squares difference test. Organ weight, clinical chemistry, haematology, urinalysis, and organ to body weight ratio data were analyzed by Dunnett’s t-test on the ranked data. Neuromuscular coordination data were adjusted by summing the time for the best 3 of 4 trials for each rat and analyzed by analysis of variance or analysis of covariance. All statistics were measured with p<0.05.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No deaths occurred. There were no clinical signs related to treatment.
BODY WEIGHT AND WEIGHT GAIN: Decreased body weight was observed in 3000-ppm females (statistically significant) and males (statistically significant only sporadically). The reported 4% reduction in body weight, while statistically significant, is of limited toxicological significance. (Table 5)
HAEMATOLOGY: There were no treatment-related findings at interim sacrifice. At terminal sacrifice, 1000-ppm females and 3000-ppm males and females had higher haematocrit and red blood cells, and in 1000-ppm and 3000-ppm females mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were lower. Although these findings appear treatment-related, they were not associated with any histopathology findings, results are not dose related, and changes were within 5% of the control. (Table 6)
CLINICAL CHEMISTRY: There was an increase in phosphorus in males at all treatment concentrations, which may be due to a low level in the control. There was a consistent increase in phosphorus in 1000-ppm and 3000-ppm females at interim and terminal sacrifice (Table 7). The toxicological significance of this finding is doubtful.
URINALYSIS: There were no treatment-related changes.
NEUROBEHAVIOUR: There were no treatment-related effects.
ORGAN WEIGHTS: There was a slight (5% or less) but significant decrease in absolute and relative testes weight in 3000-ppm males that was not associated with any change in sperm parameters or histopathology. This decrease, while statistically significant, is of limited toxicological relevance. Other changes in organ weights were related to the reduced body weight.
GROSS PATHOLOGY: There were no treatment-related findings.
HISTOPATHOLOGY: NON-NEOPLASTIC: There were no treatment-related findings.
HISTOPATHOLOGY: NEOPLASTIC (if applicable): There were no treatment-related findings.
OTHER FINDINGS: There were no treatment-related changes in sperm counts.
Effect levels
- Dose descriptor:
- NOAEC
- Effect level:
- 3 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Equivalent to 10,326 mg/m3; no toxicologically relevant findings at the highest concentration tested.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 5. Body weight data
Body weight data expressed in grams (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Day 0 |
161.28 ± 2.61 n=40 |
159.84 ± 2.58 n=40 |
159.72 ± 2.93 n=40 |
161.58 ± 2.37 n=40 |
Day 33 |
250.1 ± 3.9 n=40 |
252.3 ± 3.1 n=40 |
246.2 ± 4.4 n=40 |
245.0 ± 3.2 n=40 |
Day 61 |
305.2 ± 4.3 n=30 |
305.2 ± 3.8 n=30 |
302.3 ± 5.3 n=30 |
295.1 ± 3.7 n=30 |
Day 89 |
338.9 ± 4.2 n=30 |
340.8 ± 4.0 n=30 |
339.7 ± 5.2 n=30 |
329.0 ± 3.6 n=30 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Day 0 |
126.04 ± 1.29 n=40 |
125.30 ± 1.28 n=40 |
125.69 ± 1.28 n=40 |
125.94 ± 1.31 n=40 |
Day 33 |
164.44 ± 1.90 n=40 |
162.93 ± 1.36 n=40 |
163.82 ± 1.47 n=40 |
160.18 ± 1.48 n=40 |
Day 61 |
183.80 ± 2.47 n=30 |
181.83 ± 1.61 n=30 |
181.23 ± 1.73 n=30 |
175.41 ± 1.75 * n=30 |
Day 89 |
194.87 ± 2.62 n=30 |
194.62 ± 1.68 n=30 |
192.93 ± 2.02 n=30 |
187.08 ± 1.85 * n=30 |
Table 6. Selected Hematological Data
Hematological Data (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Haematocrit (%) (week 13) |
44.4 ± 0.5 n=20 |
43.7 ± 0.7 n=20 |
45.0 ± 0.1 n=20 |
45.3 ± 0.3* n=20 |
RBC (106/ mm3) (week 13) |
6.58 ± 0.07 n=20 |
6.49 ± 0.12 n=20 |
6.65 ± 0.03 n=20 |
6.71 ± 0.05 * n=20 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Haematocrit (%) (week 13) |
40.9 ± 0.3 n=20 |
42.5 ± 0.7 n=20 |
43.1 ± 0.8 * n=20 |
42.6 ± 0.05 * n=20 |
RBC (106/ mm3) (week 13) |
5.78 ± 0.05 n=20 |
6.01 ± 0.10 n=20 |
6.09 ± 0.11 * n=20 |
6.04 ± 0.07 * n=20 |
*Statistically significant at p<0.05
Table 7. Phosphorus levels in the blood
Clinical Chemistry Data (mean ± s.d.) |
||||
|
Males - ppm |
|||
0 |
300 |
1000 |
3000 |
|
Phosphorus mg/dL (week 7) |
6.98 ± 0.23 n=10 |
7.21 ± 0.26 n=10 |
8.18 ± 0.29 * n=10 |
7.52 ± 0.23 n=10 |
Phosphorus mg/dL (week 13) |
6.42 ± 0.15 n=20 |
7.27 ± 0.20 * n=20 |
7.22 ± 0.14 * n=20 |
7.72 ± 0.34 * n=20 |
|
Females – ppm |
|||
0 |
300 |
1000 |
3000 |
|
Phosphorus mg/dL (week 7) |
6.28 ± 0.57 n=10 |
6.39 ± 0.42 n=10 |
7.59 ± 0.37 * n=10 |
7.78 ± 0.27 * n=10 |
Phosphorus mg/dL (week 13) |
5.64 ± 0.19 n=20 |
6.07 ± 0.24 n=20 |
6.46 ± 0.24 * n=20 |
6.85 ± 0.15 * n=20 |
*Statistically significant at p<0.05.
Applicant's summary and conclusion
- Conclusions:
- The NOAEC for this study was 3000 ppm (10,326 mg/m3) based on a lack of toxicologically relevant findings at the highest concentration tested.
- Executive summary:
In a 90-day inhalation toxicity study, Neodene 6 alpha olefin was administered to forty Fischer 344 rats/sex/concentration by dynamic whole body exposure at concentrations of 0, 300, 1000, or 3000 parts per million (corresponding to 0; 1033; 3442; or 10, 326 mg/m3) for 6 hours a day, 5 days a week, for 13 weeks. Ten of the animals/sex/concentration were used for neuromuscular testing, ten of the animals/sex/concentration were sacrificed after 7 weeks of exposure, and twenty animals/sex/concentration were sacrificed after 13 weeks of exposure.
Subchronic inhalation of Neodene 6 alpha olefin for 13 weeks did not produce any adverse respiratory, neuromuscular, or testicular effects in rats. Decreased body weight was observed in 3000 -ppm females (statistically significant) and males (statistically significant only sporadically). Decreased absolute liver and kidney weights were observed in 3000-ppm females; however, these findings were considered secondary to reduced body weight in the absence of histopathological findings in these organs. There were statistically significant differences in haematology and clinical chemistry values, but the changes were slight (generally within 5% of the control), were not dose related, and/or not associated with any histopathology findings.Increased phosphorus levels were reported in males at all treatment levels and females exposed to 1000 and 3000 ppm hex-1-ene. The toxicological significance of these findings is doubtful. The NOAEC is 3000 parts per million (10,326 mg/m3) based on a lack of toxicologically relevant findings at the highest concentration tested.
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