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EC number: 203-982-0 | CAS number: 112-53-8
- 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
Endpoint summary
Administrative data
Description of key information
There are no reliable long-term repeated dose toxicity data available on dodecan-1-ol (CAS 112-53-8). In the key study, no adverse effects were seen after dietary administration of Alcohols, C14-15-branched and linear for 90 days to rats (Ito et al., 1978) which reported a NOAEL value of >3548 mg/kg bw/day. This value is supported by data from a 13-week from a reliable oral feeding study in rats using hexadecan-1-ol. This study reports a NOAEL value of > 4400 mg/kg bw/day. (Scientific Associates 1966a). In addition a read across 28-day study using octadecan-1-ol (rat, oral gavage), reported a NOAEL >1000 mg/kg bw/day (Henkel, 1985a; rel. 2). A read-across from a reliable 13-week dietary study in rats using hexan-1-ol reported a NOAEL of 1127 mg/kg bw/day (Scientific Associates Inc., 1966). No adverse effects were noted at any of the dose levels administered during the study.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Rats treated via the diet for 90 days with limited evaluation
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: no data but "young"
- Weight at study initiation: males 103.6 g, females 90.5 g
- Fasting period before study: no data
- Housing: individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data but "controlled within narrow limits"
- Humidity (%): no data but "controlled within narrow limits"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
IN-LIFE DATES: no data - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): basal laboratory diet (Purina Laboratory Chow)
- Storage temperature of food: no data - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuous in diet
- Dose / conc.:
- 0.25 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 0.5 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 1 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 2 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 4 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 6 other: %
- Remarks:
- nominal in diet
- No. of animals per sex per dose:
- 10 (treated), 20 (controls)
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no satellite groups - Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 5 days/week
- Cage side observations included: general physical appearance, gross signs of systemic toxicity and/or pharmacological effect, behaviour, mortality
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as mg/kg bw/day: Yes
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 30 and 90
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5/sex per group
- Parameters examined: microhaematocrit, haemoglobin, total and differential leukocyte count
CLINICAL CHEMISTRY: No
URINALYSIS: Yes
- Time schedule for collection of urine: days 30 and 90
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- How many animals: 5/sex per group (samples pooled)
- Parameters examined: albumin, acetone, bilirubin, colour, occult blood, sugar, pH, appearance, microscopic examination of sediment
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: brain, thyroid, heart, liver, spleen, kidneys, adrenals, gonads (testes or ovaries)
HISTOPATHOLOGY: Yes
- brain, thyroid, parathyroid, heart, lung, liver, spleen, stomach, small intestine, large intestine, pancreas, kidney, urinary bladder, adrenal, gonad, lymph node, bone, bone marrow
- all listed tissues from 5/sex from high dose and controls examined - Other examinations:
- none
- Statistics:
- Chi-squared test for comparing relative organ weights (but see 'Any other information on materials and methods')
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- 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
- one male in low dose group died during week 9; cause of death was said to be unrelated to treatment
- occasional bloody encrustations of the eyes and nose
- otherwise no effects
BODY WEIGHT
- no effects
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- food consumption 87.8% of controls in females in high dose group during week 13
- otherwise no effects
FOOD EFFICIENCY
- not examined
WATER CONSUMPTION
- not examined
OPHTHALMOSCOPIC EXAMINATION
- not examined
HAEMATOLOGY
- no effects other than "occasional aberrant value"
CLINICAL CHEMISTRY
- not examined
URINALYSIS
- high albumin, positive findings for occult blood; but no differences between treated and control groups
NEUROBEHAVIOUR
- not examined
ORGAN WEIGHTS
- some statistically significant effects (but see 'Remarks on results')
GROSS PATHOLOGY
- no effects
HISTOPATHOLOGY: NON-NEOPLASTIC
- no effects
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- no effects
HISTORICAL CONTROL DATA (if applicable)
- no data - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 127 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 243 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effects observed
- Critical effects observed:
- no
- Conclusions:
- In a reliable study, the NOAEL for Alfol 6 in rats following 13 weeks dietary exposure was 1127 mg/kg bw/day for males and 1243 mg/kg bw/day for females (highest doses tested).
- Executive summary:
Rats exposed to hexan-1-ol via the diet for 13 weeks showed no signs of significant toxicity when administered at nominal concentrations up to 1% (with staged increases at concentrations up to 6% during the last phase of the exposure period). There were no microscopic alterations recorded in the animals receiving concentrations of 6% (equivalent to 1127 mg/kg/day). Examination of testes and the ovaries did not show any abnormalities.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Draft OECD 422 Combined Repeat dose and Reproductive/Developmental Toxicity Screening Test.
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Moellegard breeding centre
- Age at study initiation: F 8 weeks, M 7 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 2/cage, steel wire cages type 3 (for males and for females up to day 20 of gestation); macrolon cages type 3 (for females from day 20 of gestation)
- Diet (e.g. ad libitum): IT chow 101, presumably ad libitum
- Water (e.g. ad libitum): acidified tapwater, ad libitum
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2
- Humidity (%): 55 +- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: no data - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): IT chow 101
- Storage temperature of food:no data
- Preparation procedure: Diet preparation involved first mixing an aqueous dodecanol solution with the barley component, which varied for each dose level. The other components of the diet were then added. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Males 41-45 days; Females approx. 54 days
- Frequency of treatment:
- continuous in the diet
- Dose / conc.:
- 1 500 ppm
- Remarks:
- approx 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 7 500 ppm
- Remarks:
- approx 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 30 000 ppm
- Remarks:
- approx 2000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: preliminary test via a dermal route
- Rationale for animal assignment (if not random): 2 days prior to the start of dosing, animals randomised into four groups with same mean body weight
- Post-exposure recovery period: none - Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Mortality, daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: males once per week; females premating once per week
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Yes, once per week
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/week: Yes
- Compound intake calculated from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Food consumption in g body weight gain/kg food per week calculated from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: males after 37 days of dosing
- Anaesthetic used for blood collection: Yes (identity - no data)
- Animals fasted: No data
- How many animals: all males
- Parameters examined: haematocrit, heamoglobin, total erythrocyte and total leukocyte count, leukocyte differential count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: males after 37 days of dosing
- Animals fasted: No data
- How many animals: all males
- Parameters examined: protein, alkaline phosphatase, alanine aminotransferase, glucose, urea, creatinine, total and free cholesterol, triglycerides
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER: animals mated for reproductive and developmental toxicity studies - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, full necropsy on all animals
ORGAN WEIGHT: males - liver, kidneys, thymus, testes, epididymides; females - liver, kidneys, thymus
ORGANS FIXED IN FORMALIN: males - liver, kidneys, adrenals, brain, heart, spleen, thymus, organs with pathological changes, testes and epididymides fixed in Bouin's solution; females - liver, kidneys, adrenals, brain, heart, spleen, ovaries, thymus, other organs with observed pathological changes
HISTOPATHOLOGY: Yes, control and top dose group, all fixed organs except thymus - Other examinations:
- Foetal examinations and reproductive parameters (reported elsewhere)
- Statistics:
- Using the SAS-stat program; analysis of variance; all statistically significant findings further evaluated by Dunnett's t-test
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- 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
- Mortality and time to death: None
- Clinical signs: None reported
BODY WEIGHT AND WEIGHT GAIN
- Body weight gain: No differences between treated and controls of either sex.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
FOOD EFFICIENCY
- Food consumption/food efficiency: No differences between treated and controls of both sexes.
- Dietary concentrations of 1500, 7500 and 30000 ppm provided nominal dose levels of 100, 500 and 2000 mg/kg bw/day; measured dose levels were 82-122, 425-642 and 1616-2646 mg/kg bw/day respectively for males and 125-136, 639-676 and 2503-3058 mg/kg bw/day respectively for females premating.
HAEMATOLOGY (see table 1)
- Haematology: (males only investigated) A dose related reduction in total WBC was observed which reached statistical significance in top and mid
dose males, there were no differences in the differential white cell count that explained these observations.
CLINICAL CHEMISTRY (see table 1)
- Clinical chemistry (males only investigated): There was a significant reduction in plasma triglyceride (TG) at the top dose level and a significant
reduction in plasma free cholesterol (F-chol) at the intermediate dose level. The reduced cholesterol level was re-analysed after removing 2 outlying
values when the statistical significance was lost. These results may have been confounded by the difference in dietary composition between
groups.
ORGAN WEIGHTS (see table 2)
- Organ weights: There were no dose related changes in organ weights. In males only there was a reduction in relative and absolute liver weights at
the low dose level and a reduction in relative liver weight at the mid dose, the top dose was comparable to controls.
GROSS PATHOLOGY
- Gross pathology: There were no changes attributable to exposure to the test compound.
HISTOPATHOLOGY
- Histopathology: There were no treatment related histopathological changes.
HISTORICAL CONTROL DATA (if applicable): none
OTHER FINDINGS
- ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
Males: 102.4, 530.8 and 2046.4 mg/kg bw/day (mean of values reported for 2 weeks prior to mating and 3 weeks after mating)
Females: 130.5, 657.5 and 2870.5 mg/kg bw/day (mean of values reported 2 weeks prior to mating) - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- < 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No adverse effect observed
- Critical effects observed:
- no
- Conclusions:
- In a reliable study conducted to the draft OECD guideline 422, an NOAEL for systemic toxicity of 2000 mg/kg bw/day (highest dose tested) was determined in male rats in the absence of toxicologically significant effects at any dose level. . The study was performed in compliance with GLP.
- Executive summary:
An oral NOAEL of 2000 mg/kg bw/day (the highest dose tested) was established in rats for dodecan-1-ol, in a combined repeat dose and reproductive/developmental toxicity screening test performed to draft OECD guideline 422 and to GLP (Hansen 1992a).
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- (no ophthalmology or neurobehavioural testing; slightly limited pathology examination; some details missing from report)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Wistar-SLC
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: 5 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: "cages" (no further details given)
- Diet (e.g. ad libitum): CE-2, made by Nihon Kurea, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): CE-2 solid food, made by Nihon Kurea
- Storage temperature of food: no data - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- continuously
- Dose / conc.:
- 0.2 other: %
- Remarks:
- Nominal in diet
- Dose / conc.:
- 1 other: %
- Remarks:
- Nominal in diet
- Dose / conc.:
- 5 other: %
- Remarks:
- Nominal in diet
- Dose / conc.:
- 169 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 702 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 3 548 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 11
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: none
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: no data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: Twice weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Evaluated twice weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY: Evaluated twice weekly
- 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 data
WATER CONSUMPTION: Weekly
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at 90 days
- Anaesthetic used for blood collection: Yes (pentabarbital) (except blood sugar sample, which was taken from the tail vein, apparently without anaesthetic)
- Animals fasted: No data
- How many animals: all
- Parameters checked: sugar, RBC and WBC (by microcell counter), Hb (by cyanomethaemaglobin method), Haemocrit (by capillary centrifugal separation method), platelet count (by platelet counter) and differential count (i.e. % of WBC; by ointment sample: GIEMSA dye).
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at 90 days
- Animals fasted: No data
- How many animals: all
- Parameters checked: Alkaline phosphatase activity, ALAT and ASAT (alanine and aspartate transaminase activities), total protein, albumin/globulin ratio, total cholesterol, urea nitrogen, sodium and potassium (using a Greiner electronic selective analyser II); glucose (using enzyme method: Tokyo Zoki Kagaku reagent).
URINALYSIS: Yes, in all animals
- Time schedule for collection of urine: at 90 days
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked: pH, protein, sugar, ketone bodies, occult blood (using Labstix by Nihon Emusu)
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC)
Macroscopic: general examination
Organ weights: brain, hypophysis, thyroid, thymus, heart, liver, kidney, spleen, adrenal, testes or ovaries.
Microscopic: the above mentioned organs plus stomach, pancreas, small & large intestine, lymph gland, bone marrow. - Other examinations:
- none
- Statistics:
- STATISTICAL METHODS: Student t test.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced at 1% and 5%
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced at 1% and 5%
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased at 1% and 5%
- Water consumption and compound intake (if drinking water study):
- no effects observed
- 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):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased relative weight of several organs in males and females at 5%
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No significant dose-related effects
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No animals died during the study and clinical signs were unremarkable.
BODY WEIGHT AND WEIGHT GAIN
Reduced at 1% and 5%
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Reduced at 1% and 5% (water consumption was also reduced at these dietary levels). Food loss due to spillage was frequently reported in these groups.
FOOD EFFICIENCY
Increased at 1% and 5%
HAEMATOLOGY
Haemoglobin was significantly reduced in top dose males (15.2 g/dl (SD +-0.5) compared to 15.9 g/dl (SD +-0.4) for controls).
Eosinophils were significantly reduced at all dose levels in males but this was not dose related (control 1.5%; low dose 0.6%; mid dose 0.2%; high dose 0.6%).
White blood cell count was significantly increased in high-dose females (100/mm3: control 47 (SD +- 12.2); top dose 73.2 (SD +-16.2)). This was not accompanied by any significant changes in the differential leucocyte count. There was no increase in WBC at the low and mid dose (mean values 45.2 and 45.5 respectively).
CLINICAL CHEMISTRY
See Table 1, below.
Alkaline phosophatase (AP) activity increased from 1%; Total protein increased at 1% and 5% in males and at 5% in females. At 5%, alanine aminotransferase activity increased (ALAT), albumin/globulin ratio (AG) increased, (in females) total cholesterol reduced and (in males) potassium increased.
URINALYSIS
No treatment-related changes
ORGAN WEIGHTS
See Table 2, below.
The most significant effects on organ weights were:
Increased relative weight of thyroid, liver and kidney in males and females at 5%.
Decreased absolute weight of brain in males and females at 5%.
At 5%:
Absolute brain & heart weights were decreased in males and females.
Absolute lung, thymus and hypophysis weights were decreased in males.
Absolute kidney and spleen weights were decreased in males (this effect was seen in the mid-dose males as well).
Absolute liver, kidney and thyroid weights were increased in females.
Relative lung and heart weights were increased in males.
Relative liver, kidney, adrenal, thyroid and hypophysis weights increased in males (adrenal and thyroid effect also seen in mid-dose males).
Relative thyroid, kidney and liver weights increased in high-dose females (the liver and kidney were also significantly affected in mid-dose females).
No biologically signficant changes in either absolute or relative organ weights were observed at the low-dose level (0.2%).
GROSS PATHOLOGY
No treatment-related effects.
Blood was observed in the stomach of 1 female in each of the mid- and high-dose groups. There were no other remarkable changes.
HISTOPATHOLOGY: NON-NEOPLASTIC
No significant treatment-related effects.
Slight kidney changes such as hyaline casts, calculi and increased medullary connective tissue were observed but these were not dose related.
In the liver slight focal necrosis was observed in 1/5 low-dose females examined; there were no histopathological changes in mid- or high-dose groups.
No abnormalites were observed in any other organs including the gonads. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 3 548 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Average dose. Effects observed on body weight, food consumption and food efficiency were considered to be attributable to lower food consumption as a result of lack of palatability. Effects noted on clinical chemistry were not considered adverse.
- Critical effects observed:
- no
- Conclusions:
- In a reliable study, conducted using a protocol similar to OECD guideline 408, male and female rats were fed diets containing 0, 0.2%, 1% or 5% Dobanol-45 (providing average intakes of 169, 747 or 3548 mg/kg bw/day, respectively) for 90 days. Effects seen at doses higher than 0.2% included increased liver enzyme activity (alkaline phosphatase and alanine aminotransferase) and increased relative weights of a number of organs, which is attributable to the reduced body weight due to lower food consumption as a result of lack of palatability. It is considered that the increases in hepatic enzymes are not adverse as there was no associated pathology. It is therefore concluded that the NOAEL is 3548 mg/kg bw/day, the highest dose tested.
- Executive summary:
The key study was performed using a protocol similar to OECD guideline 408 but prior to the introduction of GLP. The test material Alcohols, C14-15 branched and linear was administered to rats via the diet for 90 days at concentrations of 0, 0.2, 1 and 5% (providing average intakes of 169, 747 or 3548 mg/kg bw/day, respectively). The top and intermediate dose level (5 and 1%, respectively) had limited palatability and induced a considerable reduction in growth (>30% and approx. 15% reduction in body weight in high and mid dose males, respectively). Biochemistry showed increased liver enzyme activity (alkaline phosphatase and alanine aminotransferase) at the 1 and/or 5% level. It is considered that the increases in hepatic enzymes are not adverse as there was no associated pathology. The increase in relative weights of a number of organs is attributable to the reduced body weight due to lower food consumption as a result of lack of palatability. No treatment-related microscopic changes were observed, including both the testis and ovaries at this same dose level. Based on the effect on body weight a NOAEL was established at the 5% dietary incorporation level (approx. 3548 mg/kg/day) (Ito et al., 1978).
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Report in German language, English summary page.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- (no neurobehavioural testing; limited range of endpoints assessed in other examinations)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: M 84-98 g; F 81-93g
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- no data
VEHICLE
- Justification for use and choice of vehicle (if other than water): not stated
- Concentration in vehicle: 0, 2, 10 or 20%
- Amount of vehicle (if gavage): 5 ml/kg bw
- Lot/batch no. (if required): no data
- Purity: no data - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily, 5 days/week
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 (main study) + 5 (satellite groups)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: reversibility
- Post-exposure recovery period in satellite groups: 28 days
- Section schedule rationale (if not random): no data - Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: clinical signs and mortality
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION: Yes
- Time schedule for examinations: daily
FOOD EFFICIENCY: No data
WATER CONSUMPTION: Yes
- Time schedule for examinations: weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at end of study
- Dose groups that were examined: no data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 21/22 daily doses
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters examined.: Haematocrit, MCV, Hb, RBC, WBC, Thrombocytes, differential white count.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: After 21/22 daily doses
- Animals fasted: No data
- How many animals: No data
- Parameters examined: Serum urea, creatinine, Na, K, calcium, alkaline phosphatase, ALAT, ASAT, GT, bilirubin, chloride, albumin, total protein, cholesterol
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: thyroid, adrenals, thymus, kidney, spleen, heart, brain, testes, liver
HISTOPATHOLOGY: Yes, all organs from the control and top dose animals were examined plus the animals from the reversibility study. - Statistics:
- T-test. U-test for organ weights
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- 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:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No effects on mortality
Unremarkable other than top dose females appearing rather defensive when handled
BODY WEIGHT AND WEIGHT GAIN
No effects
FOOD CONSUMPTION
No effects
FOOD EFFICIENCY
No data
WATER CONSUMPTION
No effects
OPHTHALMOSCOPIC EXAMINATION
No effects
HAEMATOLOGY
No differences between treated and control animals other than an increase in neutrophils containing rodlike bodies observed in top dose females (confidence level 95%*). Values obtained (% rod like cells) were controls 2.5, low dose 3.3, mid dose 2.9, high dose 5.3*
CLINICAL CHEMISTRY
Statistically significant changes (*95% ** 99% confidence) in some clinical chemistry parameters were noted as follows:
- 500 mg/kg bw/day males increased potassium*,
- 500 mg/kg/day females increased GGT*, cholesterol** and chloride*
- glucose was elevated in top dose males (mmol/l): Control 6.03, Low 6.20, Mid 6.25, High 7.28**
These changes were not dose and/or sex related and not correlated with any histopathological findings and are therefore not considered of toxicological significance.
URINALYSIS
No effects
NEUROBEHAVIOUR
No data
ORGAN WEIGHTS
Both absolute and relative organ weights were essentially comparable in treated and control animals.
Sporadic changes were observed as follows (*95% ** 99% confidence):
- increase in absolute male kidney weight at 500 mg/kg/day*
- increase in absolute testis weight at 1000 mg/kg/day*; mean relative (absolute) testis weight: Control 0.856 (3.207), Low 0.839 (3.186), Mid 0.908 (3.455), High 0.893 (3.474*)
- the only change in relative organ weight was an increase in male adrenal weight at 1000 mg/kg/day*; mean relative (absolute) adrenal weight: Control 0.013 (0.050), Low 0.014 (0.054), Mid 0.014 (0.055), High 0.015* (0.058)
GROSS PATHOLOGY
No effects
HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment related histopathological changes in test, control or reversibility groups.
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not applicable
HISTORICAL CONTROL DATA (if applicable)
No data - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Critical effects observed:
- no
- Conclusions:
- In a reliable study, performed according to a protocol similar to OECD guideline 407, a 28-day oral NOAEL of 1000 mg/kg bw/day was determined in the rat. The study was performed in compliance with GLP.
- Executive summary:
Using a protocol similar to OECD guideline 407, a GLP study, in which male and female rats were administered hexadecan-1-ol by oral gavage on 5 days/week for 28 days, established an NOAEL of >1000 mg/kg bw/day, the highest dose tested (Henkel 1985a).
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Valid with restrictions including lack of biochemical investigations and limited reporting of statistical findings
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Rats treated via the diet for 90 days with limited evaluation
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- other: albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc.
- Age at study initiation: no data but "young"
- Weight at study initiation: males 104.1 g, females 90.5 g
- Fasting period before study: no data
- Housing: individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data but "controlled within narrow limits"
- Humidity (%): no data but "controlled within narrow limits"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
IN-LIFE DATES: no data - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): basal laboratory diet (Purina Laboratory Chow)
- Storage temperature of food: no data - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuous in diet
- Dose / conc.:
- 1 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 2.5 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 5 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 7.5 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 10 other: %
- Remarks:
- nominal in diet
- No. of animals per sex per dose:
- 10 (treated), 20 (controls)
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no satellite groups - Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 5 days/week
- Cage side observations included: general physical appearance, gross signs of systemic toxicity and/or pharmacological effect, behaviour, mortality
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Time schedule for examinations: weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as mg/kg bw/day: Yes
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: days 30 and 90
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5/sex per group
- Parameters examined: microhaematocrit, haemoglobin, total and differential leukocyte count
CLINICAL CHEMISTRY: No
URINALYSIS: Yes
- Time schedule for collection of urine: days 30 and 90
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- How many animals: 5/sex per group (samples pooled)
- Parameters examined: albumin, acetone, bilirubin, colour, occult blood, sugar, pH, appearance, microscopic examination of sediment
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: brain, thyroid, heart, liver, spleen, kidneys, adrenals, gonads (testes or ovaries)
HISTOPATHOLOGY: Yes
- brain, thyroid, parathyroid, heart, lung, liver, spleen, stomach, small intestine, large intestine, pancreas, kidney, urinary bladder, adrenal, gonad, lymph node, bone, bone marrow
- all listed tissues from 5/sex from high dose and controls examined - Other examinations:
- none
- Statistics:
- Chi-squared test for comparing relative organ weights. Original organ weight analyses using the Chi square test were supplemented by Tukey tests carried out by the Weinberg group (see 'Any other information on materials and methods')
- 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):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- all animals survived the 13 week treatment period.
- all surviving animals appeared normal
BODY WEIGHT AND WEIGHT GAIN
- significantly reduced (84.7 - 89.8% of controls) in top dose males for most study weeks, in mid dose females at weeks 4-13 and high dose females (81.7-89.7%) throughout the study
- changes were attributed at least in part to reduced food consumption and the high content of test material in the diet.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
- significantly reduced (76.4 - 89.2% of controls) in top dose males at weeks 1 and 12, in mid dose males at week 13, in mid dose females at week 1 and high dose females weeks 1 and 12 (79.1 - 89.9% of controls).
FOOD EFFICIENCY
- no data
WATER CONSUMPTION
- not examined
OPHTHALMOSCOPIC EXAMINATION
- not examined
HAEMATOLOGY
- no effects
CLINICAL CHEMISTRY
- not examined
URINALYSIS
- no effects
NEUROBEHAVIOUR
- not examined
ORGAN WEIGHTS
- the original report indicated that there were significant differences in some relative organ weights from treated groups compared to controls. These were reanalysed by the Weinberg Group using the Tukey test (see 'Remarks on results' section)
GROSS PATHOLOGY
- unremarkable
HISTOPATHOLOGY: NON-NEOPLASTIC
- there were no treatment related histopathological changes in the control and top dose animals examined (including testes & ovaries).
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
- not applicable
HISTORICAL CONTROL DATA (if applicable)
- no data - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 4 257 other: mg/kg (bw) based on highest dose tested.
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 4 567 other: mg/kg (bw) based on highest dose tested.
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effects observed
- Critical effects observed:
- no
- Conclusions:
- In a reliable study, in which rats were treated with Alfol 16 via the diet for 13 weeks, an NOAEL of >4400 mg/kg bw/day (highest dose tested) was determined. Reduced weight gain, food consumption and organ weight changes were deemed to be secondary to the high dose administered but not specific to the test substance.
- Executive summary:
For hexadecan-1-ol, oral NOAELs were > 4257 and > 4567 mg/kg bw/day in male and female rats respectively in a 90-day repeated dose toxicity test in which a somewhat limited range of endpoints was evaluated (Scientific Associates 1966a).
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily, 5 days/week
- Dose / conc.:
- 100 other: mg/kg in olive oil
- Dose / conc.:
- 500 other: mg/kg in olive oil
- Dose / conc.:
- 1 000 other: mg/kg in olive oil
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: 28 days
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effect observed
- Critical effects observed:
- no
- Conclusions:
- The NOAEL for this study is considered to be >1000 mg/kg bw/day based on a lack of toxicologically significant effects. Statistically significant changes in some clinical chemical and haematological parameters and organ weights changes were not accompanied by histopathological changes and were either not dose related or appeared in only one sex. These effects are not considered of toxicological significance.
- Executive summary:
Data are available from a 28-day repeated dose oral toxicity study in which octadecan-1-ol was administered by oral gavage to male and female rats at 0, 100, 500, 1000 mg/kg bw/day. Statistically significant changes in some clinical chemical and haematological parameters and organ weights changes were not accompanied by histopathological changes and were either not dose related or appeared in only one sex. These effects are not considered of toxicological significance, so the NOAEL is concluded to be >1000 mg/kg/day, the highest dose tested.
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- sub-chronic; short-term
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- 1. HYPOTHESIS FOR THE CATEGORY APPROACH
The hypothesis is that the category members have similar structures and properties (absence of repeated dose toxicity effects via the oral route), which are consistent across the category (Scenario 6 in the RAAF). The consistency of this property across the category is discussed in the endpoint summary.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the test material identity information within each endpoint study record.
The long chain linear aliphatic alcohol Category has at its centre a homologous series of increasing carbon chain length alcohols. The category members are structurally very similar. They are all primary aliphatic alcohols with no other functional groups. The category members are linear or contain a single short-chain side-branch at the 2-position in the alkyl chain (usually an α-methyl or α-ethyl group), which does not significantly affect the properties (‘essentially linear’). The category members have saturated alkyl chains or contain a small proportion of naturally-occurring unsaturation(s) which does not significantly affect the properties. Linear, branched and unsaturated structures are considered to have such similar properties, including metabolic pathways and products, that their inclusion in the category is well justified.
Impurities: Linear and/or ‘essentially linear’ long chain aliphatic alcohols of other chain lengths may be present. These are not expected to contribute significantly to the properties in respect of this endpoint due to predictable trends (see point 3).
There are no impurities present at above 1% which are not category members or which would affect the properties of the substance.
3. CATEGORY JUSTIFICATION
The category members are structurally very similar (see point 2) and are biochemically very similar. The metabolic synthesis and degradation pathways are well established. This Category is associated with a consistency and predictability in the physicochemical, environmental, and toxicological property data across its members.
The consistency of observations in this property across the range of chain lengths covered by this Category is described in the Endpoint Summary and in the Category Report attached in Section 13.
In this registration, the information requirement is interpolated based on read-across from members of the category with shorter and longer chain length, providing evidence of consistency in effects irrespective of variation in physico-chemical properties of specific category member substances.
4. DATA MATRIX
A data matrix for the C6-24 alcohols Category is attached in Section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Dose descriptor:
- NOAEL
- Effect level:
- 3 548 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Average dose. Effects observed on body weight, food consumption and food efficiency were considered to be attributable to lower food consumption as a result of lack of palatability. Effects noted on clinical chemistry were not considered adverse.
- Critical effects observed:
- no
Referenceopen allclose all
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
(means calculated from individual weekly dietary intake data)
0.25% M 182 mg/kg/day; F 216 mg/kg/day
0.5% M 374 mg/kg/day; F 427 mg/kg/day
1% M 1127 mg/kg/day; F 1243 mg/kg/day
Organ weights: The original report indicates that there were significant differences in some relative organ weights from treated groups compared
to controls.
Table 1: Selected haematology and clinical chemistry findings
Doses (mg/kg bw/day (nominal)) |
0 |
100 |
500 |
2000 |
male (mean and standard deviation) |
||||
Number of animals/group |
12 |
12 |
12 |
12 |
Haematology (day 37) |
|
|
|
|
- WBC (mmol/l) [sic, presumably x 109/l] |
7.0 ± 1.8 |
5.9 ± 1.3 |
4.3*** ± 1.4 |
4.7** ± 1.2 |
Blood chemistry (day 37) |
|
|
|
|
- total cholesterol (mmol/l) |
1.60 ± 0.27 |
1.74 ± 0.36 |
1.64 ± 0.30 |
1.75 ± 0.22 |
- free cholesterol (mmol/l) |
0.18 ± 0.07 |
0.16 ± 0.05 |
0.11* ± 0.06 |
0.15 ± 0.05 |
- triglyceride (mmol/l) |
0.58 ± 0.32 |
0.42 ± 0.11 |
0.45 ± 0.17 |
0.31** ± 0.06 |
* p<0.05 ** p<0.01 *** p<0.001
Table 2: Absolute and relative organ weights
|
Males (mean and standard deviation) |
||||
DAILY DOSE |
0 |
100 |
500 |
2000 |
|
NUMBER OF ANIMALS |
12 |
12 |
12 |
12 |
|
BODY WEIGHT (g)a |
370 ± 26.9 |
366 ± 20.4 |
383 ± 20.6 |
367 ± 16.7 |
|
LIVER |
|
|
|
|
|
AbsoluteWeighta |
g |
12.27 ± 1.2 |
11.20* ± 0.8 |
11.76 ± 1.0 |
11.98 ± 0.9 |
Per BodyWeighta |
% |
3.3 ± 0.19 |
3.1* ± 0.21 |
3.1* ± 0.24 |
3.3 ± 0.21 |
aGroup means at terminal necropsy are shown.
* p<0.05
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: The dose levels were based on the results of a 14 day preliminary study in which
groups of rats received 0.5, 1, 3 and 10% Dobanol 45 in the diet. As only the 10% level showed any fatalities or signs of intoxiciation the
dose levels for the 90 day study were set at 0.2, 1 and 5% in the diet. These are equivalent to mean intakes (in mg/kg bw/day) of:
males 171 (101 -317), females 167 108 -271 (0.2%);
males 759 (488 -1301), females 736 (523 -1040) (1%);
males 3626 (2660
-5659), females 3491 (2529 -4802) (5%)
Table 1
- Clinical chemistry: Significant changes from control are as shown below:
Dose AP
ALAT
T-P
A/G
T-chol
K-
Males (KA-U) (K-U)
(g/dl)
mg/dl
mEq l
Control 13.0
37.7
5.79
1.12
39.5
4.45
0.2% 13.7
46.0
5.93
1.09
40.5
4.66
1% 15.6** 36.5
5.94*
1.14
43.0
4.66
5% 16.4** 71.6**
5.52*
1.25**
42.2
4.93**
Females
Control 12.9
35.3
5.78
1.12
52.1
4.45
0.2% 12.4
36.7
5.83
1.12 52.8
4.36
1% 15.5** 35.8
5.75
1.13
52.6
4.27
5% 19.8** 99.4**
5.55* 1.28** 42.7**
4.38
Table 2 - Organ weights: The more significant changes (either seen in both sexes or dose related) in relative organ weights
expressed in mg/100g (thyroid & adrenal) or g/100g are shown in the table below.
Dose Brain
Thyroid Testes Liver Kidney Adrenal
Males
Control 0.57 4.55 0.91 3.14
0.61 11.6
0.2% 0.57 4.72 0.90 3.09
0.59 12.3
1% 0.61** 5.07* 0.98* 3.30
0.62 13.0*
5%
0.71** 5.53** 1.12** 4.08** 0.71* 15.4**
Females
Ovary
Control 0.93 6.05 31.8 2.89 0.61
26.1
0.2% 0.92 6.52 31.0 2.98
0.64 24.8
1% 0.96 6.79 32.0 3.12*
0.65** 26.0
5% 0.96 7.60** 36.8** 3.97**
0.70** 25.9
NOAEL: 1000 mg/kg/day
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
0, 100, 500 & 1000 mg/kg/day
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality and time to death: No mortalities.
- Clinical signs: Unremarkable.
- Body weight gain: Male bodyweight gain was reduced compared to controls, body weight gains were 95%, 91% and 82% of control values for low,
mid and high dose levels respectively at the end of the study. This was attributed to a high mean control bodyweight in males and marked inhibition
of bodyweight gain in one male in each of the high and mid dose levels.
- Food/water consumption: Water consumption was comparable in control and treated groups. Food consumption was slightly reduced in males
(95% confidence).
- Ophthalmoscopic examination: No treatment related ocular lesions.
- Clinical chemistry: There were some statistically significant changes (p=0.05) in clinical chemical parameters in the top dose group. In males
ASAT was increased (control mean 33 U/l; top dose 45.1); Na was also increased (control mean 143.1 mmol/l; top dose 144.4). Serum chloride
was reduced (control mean 99.7 mmol/l; top dose 97.9). In females there was an increase in Na (control mean 142 mmol/l; top dose 143) and in
phosphorous (control mean 1.99 mmol/l; top dose 21.9. These changes are not clearly dose related and apart from the slight increase in serum
sodium do not appear in both sexes. There are no histopathological changes related to these changes which were considered chance
observations and not indicative of a trend.
- Haematology: Treated and control groups were comparable. A slight increase (95% confidence *) in neutrophils with rod-like bodies (mid dose
males), a marginal decrease in thrombocytes (top dose males) and eosinophils (top dose females) were not considered of biological significance.
Thrombocytes:
Control low mid high
male 633.9 619.9 583.9 511.9*
Eosinophils:
female 1.3 0.8 0.9 0.3**
- Urinalysis: Not done
- Organ weights: Sporadic changes in absolute or relative organ weights relative weights were not dose and/or sex related. There was no
corresponding histopathological change. Relative heart weights were increased* in top dose males, Relative and absolute kidney weights were
decreased* in mid-dose females, while other absolute organ weights were changed as follows:
Absolute mean spleen weight:
Control low mid high
male 0.706 0.651 0.585* 0,593*
Absolute mean thyroid weight:
Control low mid high
male 0.024 0.018** 0.02 0.018**
Absolute mean spleen weight:
Control low mid high
male 0.706 0.651 0.585* 0.593*
Relative mean heart weight:
Control low mid high
male 0.281 0.288 0.302 0.314*
- Pathology: There were no treatment related findings. Pathological changes observed were related to misdosing, respiratory infection or viral
infection.
STATISTICAL RESULTS: T-test and U-test for organ weights.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 3 548 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
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
A combined repeat dose and reproductive/developmental toxicity screening test is available for dodecan-1-ol. The key study was selected from data for substances with similar human health and physicochemical properties and therefore absorption properties to the registration substance. As no adverse systemic effects were observed for category members, the study using the highest dose from the available data was selected as key. The available repeated dose toxicity data for long chain alcohols have been reviewed and discussed, with the conclusion that the long chain alcohols are of low systemic toxicity (Veenstra G, Webb C et al., 2009). A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2021).
The key study was performed using a protocol similar to OECD Test Guideline 408 but prior to the introduction of GLP. The test material Alcohols, C14-15 branched and linear was administered to rats via the diet for 90 days at concentrations of 0, 0.2, 1 and 5% (providing average intakes of 169, 747 or 3548 mg/kg bw/day, respectively). The top and intermediate dose level (5 and 1%, respectively) had limited palatability and induced a considerable reduction in growth (>30% and approx. 15% reduction in body weight in high and mid dose males, respectively). Biochemistry showed increased liver enzyme activity (alkaline phosphatase and alanine aminotransferase) at the 1 and/or 5% level. It is considered that the increases in hepatic enzymes are not adverse as there was no associated pathology. The increase in relative weights of a number of organs is attributable to the reduced body weight due to lower food consumption as a result of lack of palatability. No treatment-related microscopic changes were observed, including both the testis and ovaries at this same dose level. Based on the effect on body weight a NOAEL was established at the 5% dietary incorporation level (approx. 3548 mg/kg/day) (Ito et al., 1978).
The Category hypothesis is that the long chain linear aliphatic alcohol category has at its centre an homologous series of increasing carbon chain length, which is associated with a consistency and predictability in the property data across the group, for the physicochemical, environmental and toxicological property data sets. In view of the structural and chemical similarities, it is considered that the results from a number of reliable repeated dose toxicity studies on single- or multiple-constituent alcohols with appropriate chain lengths can be read across to dodecan-1-ol. A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2021).
For hexan-1-ol, oral NOAELs were 1127 and 1243 mg/kg bw/day (the highest doses tested) in male and female rats respectively in a 90-day repeated dose toxicity test in which a somewhat limited range of endpoints was evaluated (Scientific Associates 1966a).
For hexadecan-1-ol, oral NOAELs were > 4257 and > 4567 mg/kg bw/day in male and female rats respectively in a 90-day repeated dose toxicity test in which a somewhat limited range of endpoints was evaluated (Scientific Associates 1966a). Using a protocol similar to OECD guideline 407, a GLP study, in which male and female rats were administered hexadecan-1-ol by oral gavage on 5 days/week for 28 days, established an NOAEL of >1000 mg/kg bw/day, the highest dose tested (Henkel 1985a).
An oral NOAEL of 2000 mg/kg bw/day (the highest dose tested) was established in rats for dodecan-1-ol, in a combined repeat dose and reproductive/developmental toxicity screening test performed to draft OECD guideline 422 and to GLP (Hansen 1992a). No maternal toxicity was seen in rats after oral gavage dosing with Alcohols C7-11 branched and linear at up to 1440 mg/kg bw/day on days 6 to 15 of gestation and this top dose was therefore the NOAEL (Hellwig & Jäckh 1997).
A sub-acute oral study is available for Alcohols, C12-13, branched and linear in which the test substance was administered by oral gavage. The study was conducted to OECD guideline 407 and in compliance with GLP (TNO, 1999). The study authors concluded a NOAEL of 300 mg/kg bw/day, however the reported liver findings were not accompanied by histopathological changes and it is concluded that the NOAEL is 1000 mg/kg bw/day.
For Alcohols, C12-16, data are available from a research publication in which the test material was dissolved in polyethylene glycol 300 and administered to male rats by oral gavage at 209 mg/kg bw/day for 14 days. There were no adverse effects on the small number of endpoints measured (liver and testis weight and histopathological examination of the liver). An NOAEL of 209 mg/kg bw/day was identified from this limited study (Central Toxicology Laboratory, 1984).
In a limited study, conducted prior to the introduction of GLP, Alcohols C16-18 and C18 unsaturated. was administered to male and female at a single dose level of 840 mg/kg bw/day by oral gavage and no toxicity was reported (Henkel 1973).
No repeated dose toxicity studies were available on any of the long chain linear aliphatic alcohol category by the dermal route. No reliable guideline repeated dose toxicity studies were available on any of the relevant members of the long chain linear aliphatic alcohol category by the inhalation route.
Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:
In summary, the sub-category of the linear LCAAs is of a low order of toxicity upon repeated exposure. The LCAAs at lower end of this group caused local irritation at the site of first contact and induced signs of depression and respiratory effects when administered at very high dose levels and only as a bolus dose (C6, C8 alcohol) in the dog (C6 alcohol) and the rat (C8 alcohol). Other routes of exposure induced no apparent neurotoxicity either centrally or peripherally. Intermediate (>C8 to C12) and higher (>C12) linear LCAAs are non-irritant at the site of first contact and are without a neurotoxic potential. At high dose levels some of the higher LCAAs showed changes in clinical chemistry and liver weight but without further evidence of systemic toxicity; this finding may be indicative of mild, sub-clinical effects in the liver. There are no species differences observed for this sub-category, based on a comparison of the results of parallel studies in the rat and the dog.
In summary, the data for the essentially linear LCAAs, including the data from supporting substances, indicate a low order of toxicity upon repeated exposure. A consistent finding for this group is the effect on the liver: mild organ weight increases and/or slight clinical chemical changes but without evidence of significant histopathological effects. The clinical chemistry changes were generally of a slight grade but showed some inconsistencies, some of which relating to decreases in transferase activity, a change not normally associated with adverse hepatic effects. The (small) degree of the liver weight increases, the pattern of the clinical chemical changes and the absence of markers support the conclusion that this sub-category of LCAAs lacks a potential for the induction of peroxisomal proliferation. There is evidence of irritation at the first site of contact for the lower members of this group.
Conclusion:
The repeat dose toxicity of the category of LCAAs with chain lengths ranging from C6 to C22 indicates a low order of toxicity upon repeated exposure. Typical NOAEL’s recorded for this category range between approx. 200 mg/kg/day to 1000 mg/kg/day in the rat upon sub-chronic administration via the diet. No adverse systemic effects have been seen in reliable studies with members of the Category of C6-24 Alcohols, therefore the NOAELs represent the highest dose tested. At the lower end, members of this category induce local irritation at the site of first contact. Other notable findings observed for several members within this group suggest mild changes consistent with low-grade liver effects with the changes in essentially linear LCAAs being slightly more pronounced than in linear alcohols. Typical findings include: slightly increased liver weight, in some cases accompanied by clinical chemical changes but generally without concurrent histopathological effects. Special studies demonstrated that this category does not have a potential for peroxisome proliferation. A potential for depression as observed for short chain aliphatic alcohols (C1 to C4; not included in this category) was also identified for hexan-1-ol and octan-1-ol, however this effect was only expressed upon repeated administration of a bolus dose; effects were absent upon inhalation or dietary administration. Similarly, hexan-1-ol and octan-1-ol induced respiratory distress upon repeated administration of a bolus dose. LCAAs do not have a potential for peripheral neuropathy. Furthermore, the data from the substances supporting this category (i. e. isoamyl alcohol), demonstrate that the toxicological profile of the repeated dose toxicity of 100% branched alcohols is qualitatively similar to that of the corresponding essentially linear alcohols. Chronic and sub-chronic toxicity studies have shown that LCAAs are of low toxicity. Furthermore, combined repeated-dose studies with developmental endpoints, as well as reproductive and developmental studies showed no effects at the highest dose tested. Where data gaps exist, the gap is filled by read-across from reliable evidence within the C6-24 Alcohols Category, where possible using interpolation between at least two reliable studies using higher and lower carbon number test substances.
Repeated dose toxicity data for the Category
|
CAS |
CHEMICAL NAME |
Species/ Study type/ Duration 1 |
Route |
NOAEL
(Ref) |
Rel. |
C5 |
123-51-3 |
Isoamyl alcohol (supporting) |
Rat 17 wk |
Gavage |
500 mg/kg |
2 |
C6 |
111-27-3 |
Hexan-1-ol |
Dog 13 wk |
Diet |
370 mg/kg |
2
|
C6 |
111-27-3 |
Hexan-1-ol |
Rat 13 wk |
Diet |
1127 mg/kg (Sc.Assoc.1966) |
2
|
C6 |
111-27-3 |
Hexan-1-ol |
Rat 3 wk |
Diet |
1000 mg/kg bw/day (Moody, 1978-1982) |
2 |
C8 |
111-87-5 |
Octan-1-ol |
Rat |
gavage |
130 mg/kg (Hellwig, 1997) No systemic toxicity expected based on read across of a dermal study on Fatty Alcohol Blend of which octan-1-ol is a constituent, and on read-across from an oral study on hexan-1-ol. No adverse systemic effects were observed at the highest dose in either study. |
2 |
C9 |
143-08-8 |
Nonan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
|
C10 |
112-30-1 |
Decan-1-ol |
|
|
No systemic toxicity expected based on read across of a dermal study on Fatty Alcohol Blend of which decan-1-ol is a constituent, and on read-across from an oral study on hexan-1-ol. No adverse systemic effects were observed at the highest dose in either study. |
|
C11 |
112-42-5 |
Undecan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C12 |
112-53-8 |
Dodecan-1-ol |
Rat 5wk |
Diet |
2000 mg/kg (Hansen,1992a) |
2 |
C13 |
112-70-9 |
1-Tridecan-1-ol (supporting) |
Rat 2 wk |
Gavage |
184 mg/kg (Rhodes, 1984) |
2 |
C14 |
112-72-1 |
Tetradecan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C15 |
629-76-5 |
Pentadecan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C16 |
36653-82-4 |
Hexadecan-1-ol |
Rat 4 wk
|
Diet
|
>1000 mg/kg (Henkel, 1985a)
|
2
|
C16 |
36653-82-4 |
Hexadecan-1-ol |
Dog 13 wk
|
Diet
|
>1054 mg/kg (Sc.Assoc, 1966b) |
2 |
C16 |
36653-82-4 |
Hexadecan-1-ol |
Rat 13 wk |
Diet
|
>4257 mg/kg |
2 |
C18 |
112-92-5 |
Octadecan-1-ol |
Rat 4 wk
Rat 5 wk |
Gavage
Diet |
>1000 mg/kg (Henkel, 1986a) 2000 mg/kg (Hansen, 1992b) |
1
2 |
C18 |
143-28-2 |
9-Octadecen-1-ol, (9Z)- |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C20 |
629-96-9 |
Icosanan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C22 |
661-19-8 |
Docosan-1-ol |
Rat 26 wk |
Gavage |
1000 mg/kg (Iglesias,2002a) |
1
|
C22 |
661-19-8 |
Docosan-1-ol |
Dog 26 wk |
Gavage |
2000 mg/kg (Iglesias,2002b) |
1 |
C24 |
506-51-4 |
Tetracosan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
|
C8 |
60435-70-3 |
2-methylheptan-1-ol |
|
|
|
|
C9 |
68515-81-1 |
Nonan-1-ol, branched and linear |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
|
C10 |
90342-32-8 |
Decan-1-ol, branched and linear |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C11 |
128973-77-3 |
Undecan-1-ol, branched and linear
|
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
|
C13 |
90583-91-8 |
Tridecan-1-ol, branched and linear (supporting) |
|
|
Low systemic toxicity expected |
2 |
C15 |
90480-71-0
|
Pentadecan-1-ol, branched and linear |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
2 |
C7-9 |
|
Alcohols, C7-9 |
Rat 1-wk
Rat 1 wk |
Gavage
Gavage |
4175 mg/kg 128 mg/kg(Rhodes, 1984) |
2
2 |
C8-10 |
|
Fatty Alcohol Blend |
rat 90 day |
dermal |
1000 mg/kg bw/day (WIL Research, 1995) |
2 |
C9-11 |
|
Alcohols, C9-11 |
Rat 2 wk |
Gavage |
<4150 mg/kg(Brown, 1970) |
2 |
C9-11 |
|
Alcohols, C9-11- branched and linear |
Rat 9-day |
Inhalation |
<4150 mg/kg(Brown, 1970) |
2 |
C11 |
|
Reaction mass of 2-methyldecan-1-ol and 2-propyloctan-1-ol and 2-ethylnonan-1-ol and 2-butylheptan-1-ol |
|
|
No systemic toxicity expected based on data for category indicating no adverse systemic effects at highest dose tested. |
|
C12-13 |
75782-86-4 |
Alcohols, C12-13 |
Rat 4wk
|
Gavage
|
300 mg/kg; (Sasol, 1999 |
1 |
C12-13 |
740817-83-8 |
Alcohols, C12-13-branched and linear |
Rat 4wk (read-across)
|
Gavage
|
300 mg/kg; (Sasol, 1999 |
1 |
C12-15 |
90604-40-3 |
Alcohols, C12-15-branched and linear |
Rat 2 wk |
Gavage
|
209 mg/kg(Rhodes, 1984) |
2 |
C14-15 |
75782-87-5 |
Alcohols, C14-15 |
Rat 90 day |
Diet |
167 mg/kg; |
2 |
C14-15 |
|
Alcohols, C14-15-branched and linear |
Rat 90 day (read-across) |
Diet |
167 mg/kg; |
2 |
References
PFA (2021). C6-24 Alcohols Category Report: Human Health. Version number: 01. Peter Fisk Associates Ltd. 2021.
Veenstra G, Webb C et al., (2009) Human health risk assessment of long chain alcohols. Ecotoxicology and environmental safety 71 1016-1030.
Justification for classification or non-classification
Based on the available data dodecan-1-ol would not be classified for specific target organ toxicity-repeated exposure according to Regulation (EC) No. 1272/2008 (CLP) since no adverse effects occurred at <100 mg/kg bw/day. Tests on similar substances included in this category are also supportive of these results, which do not warrant classification under GHS criteria.
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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