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EC number: 921-728-3 | CAS number: 64741-66-8
- 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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Endpoint summary
Administrative data
Description of key information
Inhalation
Inhalation
systemic NOAEC (Rat): 8117 mg/m3 (similar to OECD TG 413)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 April 1978 - 30 March 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions. Limited documentation on animal housing, only 2 concentrations tested, exposure duration 84 days, no ophthalmological examination.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass. 01887
- Age at study initiation: males 6 wks, females 7 wks
- Weight at study initiation: males 185 g mean (range 165-217 g); females 162 g mean (range 138-189)
- Fasting period before study: no
- Housing: paired in chamber, individual out of chamber
- Diet (e.g. ad libitum): Standard laboratory pellet diet (Purina Laboratory Chow) ad libitum (out of chamber only)
- Water (e.g. ad libitum): ad libitum (out of chamber only)
- Acclimation period: 13 days - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Remarks on MMAD:
- MMAD / GSD: not applicable, vapour
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass chambers with 1 cubic meter total volume (760 L effective volume)
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Temperature, humidity, pressure in air chamber:
- Air flow rate: 134 L/min
- Air change rate: 8 per hour
- Method of particle size determination: not applicable, vapour
TEST ATMOSPHERE
- Brief description of analytical method used: Atmospheric sampling was performed using a Wilks Scientific Corp., Miran 1A Ambient Air Analyzer (long pathlength infrared). A calibration curve relating the absorption to the airborne concentration of the test material was prepared. On each exposure day, three samples were drawn from each exposure chamber (at about 1, 3, and 5 hours) and the exposure concentration calculated by comparing the absorption of this sample to the standard curve.
In addition, the composition of the test atmosphere was analyzed for homogeneity by gas chromatographic analysis of several charcoal-trapped vapour samples collected from each chamber during the 12-wk exposure period - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The test atmosphere was analysed for concentration and homogeneity by measurement of the infrared spectrum and by gas chromatographic analysis, respectively. Based on the infrared analysis the animals were exposed to cumulative mean concentrations of 385 and 1200 ppm, respectively. Gas chromatographic analysis of the chamber atmosphere demonstrated that the test material composition was representative of the initial sample.
- Duration of treatment / exposure:
- 12 weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
- Remarks:
- Doses / Concentrations:
400, 1200 ppm
Basis:
nominal conc. - No. of animals per sex per dose:
- 35
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Rationale for animal assignment (if not random): assigned to group by weight
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: incidence of abnormal signs
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly (full recorded physical assessment)
BODY WEIGHT: Yes
- Time schedule for examinations: weekly, from 5 days prior to exposure through termination
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes (retro-orbital sinus)
- Time schedule for collection of blood: 4, 8, 12 weeks
- Anaesthetic used for blood collection: Yes (exsanguination under ether anesthesia)
- Animals fasted: Yes (fasted overnight prior to bleeding)
- How many animals: 10/sex/group (4 and 8 weeks), 15/sex/group (12 weeks, all survivors)
- Parameters examined: hemoblobin, hematocrit, erythrocyte count, clotting time, total and differential leukocytes
CLINICAL CHEMISTRY: Yes (retro-orbital sinus)
- Time schedule for collection of blood: 4, 8, 12 weeks
- Animals fasted: Yes (exsanguination under ether anesthesia)
- How many animals: 10/sex/group (4 and 8 weeks), 15/sex/group (12 weeks, all survivors)
- Parameters examined: blood urea nitrogen, serum glutamic pyruvic transaminase (SGPT), glucose, alkaline phosphatase
OTHER:
Organ weights and organ/body weight ratios determined in animals sacrificed at 4, 8 and 12 weeks (adrenals, brain (sans pituitary), gonads, kidneys, liver, lungs) - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes: adrenals, brain (without pituitary), gonads, kidneys, liver, lungs
HISTOPATHOLOGY: Yes (control and 1200 ppm group): adrenals (2), bone marrow (sternal), brain (2 sections), eye, gonad, heart (with coronary vessels) intestine, colon, duodenum, ileum, kidneys (2), liver (2 sections), lung (2 sections), lymph node (mesenteric), mammary gland, pancreas, pituitary, salivary gland, skeletal muscle, skin, spinal cord (cervical), spleen, stomach, thyroid, trachea, urinary bladder, uterus/prostate, gross lesions, tissue masses - Statistics:
- Body weight, hematology and clinical chemistry parameters, organ weights and organ/body weight ratios were statistically evaluated. Mean values for all treatment groups were compared to the control group at each time interval (4, 8, and 12 weeks). Hematology and clinical chemistry parameters were compared by the F-test and Student's t-test. When variances differed significantly (F-test), Student's t-test was appropriately modified using Cochran's approximation (t'). Body weight, organ weight and organ/body weight ratios were compared to control according to Dunnett.
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- 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:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No treatment-related mortality occured (1 male of the 1200 ppm group was accidentally killed).
Several animals in all groups exhibited dry rales and red and mucoid nasal discharge (more numerous in the treated groups, but not clearly treatment-related), moist rales, excessive lacrimation, hair loss and chromodacryorrhea were found in a limited number of animals in all groups (not treatment-related)
1200 ppm: singular occurrences of excessive salivation, laboured, irregular breathing; yellow staining of the anogenital fur in 6 males and 35 females from wk 3 through 12
400 ppm: yellow staining of the anogenital fur in 2 females
Control: singular occurrences of excessive salivation and bleeding inside the ear; a limited number of animals with brown staining of the ano-genital region and soft stool; three observations (in one animal) of an abnormally dark red or red and yellow eye
BODY WEIGHT AND WEIGHT GAIN
1200 ppm: mean body weights in males significantly higher at wk 2 and significantly lower (p?0.05) from wk 8 through 11 than in controls
400 ppm: mean body weight and weight gains in males similar to control throughout the study, except wk 2 (significantly higher, p?0.01), in females mean body weights significantly depressed (p?0.01 and p?0.05) at wk 5 through 8.
HAEMATOLOGY
Several statistically significant (p < 0.05 and p < 0.01) decreases in mean hematocrit values of males and females of both treated groups at wk 4 and 8, statistically significant decreases (p?0.05) in mean hemoglobin values at wk 8 in the males of both treated groups and the females of the 400 ppm group at wk 4. Mean red blood cell values were significantly decreased in 1200 ppm males at wk 8 and 400 ppm females at wk 12. Since all values were within normal biological limits, these findings were not considered to be treatment-related.
CLINICAL CHEMISTRY
Mean SGPT levels were significantly (p?0.01) depressed in 1200 ppm males at wk 4, 400 and 1200 ppm males at wk 8, and in 1200 ppm females at wk 12. Mean blood urea nitrogen levels were significantly increased in the males of both treated groups at wk 8. Mean glucose levels were significantly (p?0.01 or p?0.05) increased in 400 ppm males at wk 8, decreased in 1200 ppm males at wk 12, and decreased in 1200 ppm females at wk 4 and 12. The observed effects were not considered to be treatment-related.
ORGAN WEIGHTS
Mean kidney weights and kidney/body weight ratios were significantly (p?0.05) higher in the 1200 ppm males at wk 8. In the 400 ppm males these values were also elevated, but not statistically significant. At wk 12, mean kidney weights and kidney/body weight ratios for 400 and 1200 ppm males were significantly (p?0.01) elevated, indicating a treatment-related response. The only other statistically significant (p?0.05) findings were elevated mean adrenal/body weight ratios for the 1200 ppm males at wk 4 and the 400 ppm females at wk 12.
GROSS PATHOLOGY
Microscopic evaluation of organs and tissues from the control and high level exposure groups revealed a mild tubular injury in the kidneys of some exposed male rats sacrificed after exposure for 8 and 12 wk. Other changes were unrelated to group or sex and were considered to be spontaneous.
HISTOPATHOLOGY: NON-NEOPLASTIC
See Gross Pathology - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1 200 ppm (nominal)
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- In a 12 -week inhalation study with rats the test substance hydrocarbons, C7 -C9, isoalkanes was tested. Significantly increased mean kidney weights and kidney/body weight ratios were observed in males at 400 ppm, which were considered to be treatment-related by the authors of the study.
The kidney was confirmed as potential target organ for the test material-induced toxicity by the observation of mild tubular injury found in the histopathological examination of high dose males.
The fact, that these effects were strictly limited to male rats and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats due to their exclusive expression of ?2u-globulin, the protein known to play the crucial role in the onset of this disease, the observed effects in the kidney have to be regarded as species-specific and therefore not relevant for risk assessment in humans. Therefore, these effects were not considered for the determination of the NOAEC.
Renal effects were strictly limited to males, therefore the authors concluded an ?2u-globulin-related mechanism for the observed nephropathy. The observation was not considered for determination of the NOAEC. - Executive summary:
In a 12 -week inhalation study with rats the test substance hydrocarbons, C7 -C9, isoalkanes was tested. Significantly increased mean kidney weights and kidney/body weight ratios were observed in males at 400 ppm, which were considered to be treatment-related by the authors of the study. The kidney was confirmed as potential target organ for the test material-induced toxicity by the observation of mild tubular injury found in the histopathological examination of high dose males. The fact, that these effects were strictly limited to male rats and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats due to their exclusive expression of ?2u-globulin, the protein known to play the crucial role in the onset of this disease, the observed effects in the kidney have to be regarded as species-specific and therefore not relevant for risk assessment in humans. Therefore, these effects were not considered for the determination of the NOAEC. Renal effects were strictly limited to males, therefore the authors concluded an ?2u-globulin-related mechanism for the observed nephropathy. The observation was not considered for determination of the NOAEC.
Reference
Significantly increased mean kidney weights and kidney/body weight ratios were observed in males at 400 ppm, which were considered to be treatment-related by the authors of the study.
The kidney was confirmed as potential target organ for the test material-induced toxicity by the observation of mild tubular injury found in the histopathological examination of high dose males.
The fact, that these effects were strictly limited to male rats and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats due to their exclusive expression of alpha-2u-globulin, the protein known to play the crucial role in the onset of this disease, the observed effects in the kidney have to be regarded as species-specific and therefore not relevant for risk assessment in humans. Therefore, these effects were not considered for the determination of the NOAEC.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Key inhalation toxicity data is available for Hydrocarbons C7-C9, isoalkanes. This information is supported by data available for structural analogues, Light catalytic reformed naphtha distillate and Light alkyl naphtha distillate and presented in the dossier. This data is read across to Hydrocarbons C7-C9, isoalkanes based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.
Inhalation
Hydrocarbons C7-C9, isoalkanes
Systemic toxicity of hydrocarbons, C7-C9, iso-alkanes was assessed in a 12-week inhalation toxicity study in rats (ExxonMobil Chemical,1979). In this study, repeated exposure to 400 or 1200 ppm of the test substance for 6 hours/day, 5 days/week, for 12 weeks resulted in male rat kidney effects consistent with the alpha-2µ-globulin-induced nephropathy in male rats. There was no treatment-related mortality and clinical findings were unremarkable. Under the test conditions, the NOAEC (excluding male rat nephropathy) was determined to be >1200ppm.
The fact, that alpha-2µ-globulin-induced nephropathy was strictly limited to male rats and that the test substance belongs to a category of substances which are known for their ability to induce nephropathy in male rats due to their exclusive expression of alpha-2µ -globulin, the protein known to play the crucial role in the onset of this disease, the observed effects in the kidney have to be regarded as species-specific and are not relevant for risk assessment in humans. Therefore, additional experimental data were used to evaluate repeated dose toxicity via inhalation.
Light alkylate naphtha distillate
A 13-week inhalation toxicity study was conducted using wholly vaporized light alkylate naphtha distillate (LAND-2) generated in nitrogen (Schreiner et al., 1998). Male and female rats were exposed by inhalation in whole-body exposure cages 6 hours/day, 5 days/week for 13 weeks at analytical concentrations of 0, 668, 2220, and 6646 ppm. All animals survived the treatment period and were sacrificed according to study design at the end of week 13 or 18 (recovery group). No test-related observations were noted in the exposure chambers during any exposure period for any treatment groups or during non-exposure periods. From weekly clinical observations, the only apparent treatment-related finding was an increased incidence of red facial staining in both male and female rats in the high dose group. At week 13, there were statistically significant dose-related increases in absolute and relative kidney weights in males of all 3 treatment groups. The kidney weights of high-dose males remained elevated after the recovery period. These increases correlated with microscopic observations of hyaline droplet formation in the proximal convoluted tubules considered to contain an alpha2-microglobulin-hydrocarbon complex as well as an increase in incidence and severity of nephropathy and dilated tubules at the corticomedullary junction. These microscopic finding are characteristic of "light hydrocarbon nephropathy" also known as hyaline droplet nephropathy and are male rat specific. Therefore these effects are not considered to be relevant to humans. Statistically significant increases in absolute and relative liver weights were observed in high-dose male and female rats at week 13 after sacrifice. Differences were not present after the recovery period and had no microscopic correlate. Thus, the NOAEC for systemic toxicity was 8117 mg/m³ corresponding to 2200 ppm.
In another study of Schreiner et al. (2000) conducted according to OECD 413, rats were exposed to light catalytic reformed naphtha distillate via whole body inhalation at 0, 750, 2490 or 7480 ppm (analytical conc.). Male and female rats were exposed for 6 hours/day, 5 days/week, for 13 weeks. All animals survived to study termination. The increased relative kidney weights and microscopically observed hyaline droplet formation and renal tubule dilation in high dose males reflected the occurrence of alpha-2µ-globulin-induced nephropathy, effects in male rats which have been determined to have no relevance to humans. The increased spleen weights and hematological changes had no microscopic correlate and appeared reversible with 4 weeks of recovery. There were no neurobehavioral effects observed during the study and the increased motor activity in recovery high dose males were not supported by other behavior changes or microscopic abnormalities in neural tissues, suggesting the observation may have been fortuitous. Therefore, the NOAEC was 2490 ppm.
The NOAEC of the inhalation study of Schreiner et al. (1998) conducted with light alkylate naphtha distillate was taken forward to evaluate the risk potential of hydrocarbons, C7-C9, iso-alkanes.
Justification for classification or non-classification
Based on available substance specific and read across data, Hydrocarbons, C7-C9, isoalkanes does not meet the criteria for classification for repeated dose toxicity (STOT-RE) under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).
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.
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