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EC number: 801-829-8 | CAS number: 1247790-47-1
- 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
The weight of evidence approach is done with nine studies on acute oral toxicity corresponding to three different molecules tested. As the target substance of this dossier, two of the substances tested are also secondary alcohols with a branched alkyl chain, including an isopropyl group at the end of the alkyl chain: 2,6-Dimethyl-4-heptanol (CAS 108-82-7) and 4-Methyl-2-pentanol (CAS 108-82-7). The third molecule is a secondary alcohol but with a linear alkyl chain: 2-Heptanol (CAS 543-49-7).
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Experimental result for an structural analogue. Peer-reviewed data, it is assumed that variety of data sources have been consulted, that the test methodology and identity of the test substance has been evaluated, and that a reliable and representative value for the endpoint has been selected.
- Qualifier:
- no guideline available
- Guideline:
- other: not detailed
- GLP compliance:
- not specified
- Test type:
- other: no data
- Species:
- rat
- Sex:
- male
- Route of administration:
- oral: unspecified
- Details on oral exposure:
- single dose
- Doses:
- 4 doses: 1000, 2000, 4000 and 8000 mg / Kg of bodyweight
- No. of animals per sex per dose:
- 5 males per dose
- Control animals:
- not specified
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 3 560 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 1 430 - <= 8 860
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- This substance is regarded as not classified for acute oral toxicity according to REGULATION (EC) No 1272/2008 (CLP) as LD50 > 2.000 mg/Kg of bodyweight.
- Executive summary:
- Five rats per dose were given a single dose
of 2,6-dimethyl-4 -heptanol
at 1000, 2000, 4000, and 8000 mg/kg bodyweight. Observations for mortality
and or systemic effects were made for 14 days. The acute oral LD50 in rats
was calculated to be 3560 mg/kg of bodyweight, with a 95% confidence
interval of 1430 – 8860 mg/kg of bodyweight).
Reference cited: Smyth, H.F., Carpenter, C.P., Weil, C.S., 1949. Range-finding toxicity data, list III. The Journal of Industrial Hygiene and Toxicolology 31 (1), 60–62.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 560 mg/kg bw
Additional information
In the peer-reviewed article: Belsito, D., Bickers, D., Bruze, M., Greim, H., Hanifin, J.H., Rogers, A.E., Saurat, J.H., Sipes, I.G., Smith, R.L., Tagami, H., 2010. "A safety assessment of branched chain saturated alcohols when used as fragrance ingredients". Food and Chemistry Toxicology 48 (S4), S1–46.", fifteen alcohols which are used as fragrance ingredients have been reviewed. All showed a low order of acute oral toxicity. The most relevant tests for deriving an acute oral toxicity for the substance described in chapter 1 of this dossier have been included in the endpoints under chapter 7.2.1.
According to this article, the alcohols assessed are expected to follow common metabolic pathways due to their structural similarity:
– conjugation of the alcohol group with glucuronic acid and posterior excretion
– In mammals, the metabolism of secondary alcohols proceeds primarily through their respective ketones.
– oxidation of the alcohol group;
– side-chain oxidation yielding polar metabolites, which may be conjugated and excreted – or further oxidized to an aldehyde, a carboxylic acid, and to CO2; Intermediary reactive products of oxidation of primary alcohols are aldehydes, which are toxic and possibly genotoxic, although no relevant genotoxicity was shown with the primary alcohols tested.
– excretion of the unchanged parent compound.
As all the acute oral toxicity studies found showed a low order of toxicity it is therefore concluded that metabolism yields innocuous metabolites and/or leading to rapid metabolic clearance. Considering the above metabolism information, due to the structural similarities, the target substance is expected to follow the same metabolic pathways.
Four studies have been introduced for 2,6-Dimethyl-heptan-4-ol. This molecule is considered to be the most similar to the target substance, as is also a branched secondary alcohol with nine carbons, with clear similarities on the structure as it also has an isopropyl group at the end of the alkyl chain. Like other secondary alcohols, In mammals it’s main metabolite is the corresponding ketone (2,6-dimethylheptan-4-one). The target substance is considered to have a similar metabolic pathway. In all the four studies the oral LD50 is clearly above 2000 mg / Kg of bodyweight. In rats oral LD50 have been: 3560 mg/kg bw (Smyth, et al, 1949. Range-finding toxicity data, list III), 6350 mg/kg (McOmie WA, Anderson HH, 1949. Comparative toxicologic effects of some isobutyl carbinols and ketones) and 4350 mg/kg bw (Posternak, J.M., 1975. Toxicology tests on flavouring matters. II). In this last study necropsy results done at week 12 showed organ weights and organ histopathology to be within normal limits. In another study in mice the result was 5000 mg/kg (McOmie WA, Anderson HH, 1949. Comparative toxicologic effects of some isobutyl carbinols and ketones).
Three experimental studies are included on 4 -methylpentan-2 -ol. This substance is also a branched secondary alcohol with an isopropyl group at the end of the alkyl chain, but with 6 carbons. References indicate It's main metabolite is also it's corresponding ketone (methylisobutyl ketone) and that part of the substance is excreted via it's glucuronide derivative. In all three studies the LD50 is clearly above 2000 mg / kg of bodyweight. In detail, one expermiental study in rats LD50 was 2590 mg/kg bw (Bar, V.F., Griepentrog, F., 1967) and in the other 2950 mg/kg bw (Smyth et al., 1951). Finally in the third, the LD50 value in rats was calculated to be 2590 mg/kg from a thermodinamical solubility parameter: delta c (Nishimura, H., Saito, S., Kishida, F., Matsuo, M., 1994. Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta)).
Finally, two experimental studies are detailed for 2 -heptanol. This substance is a secondary alcohol but with a linear alkyl chain. In both studies LD50 was clearly above 2000 mg/Kg of bodyweight. In one study the LD50 in femals rats was reported to be 2580 mg /Kg (Range-finding toxicity data. List V by H.F. Smyth Jr., C.P. Carpenter, C.S. Weil and U.C. Pozzani) and in the other the LD50 value in rats was calculated to be also 2580 mg/kg from a thermodinamical solubility parameter: delta c (Nishimura, H., Saito, S., Kishida, F., Matsuo, M., 1994. Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta)).
The calculated physico-chemical properties of these source substances have been detailed in the endpoints. These values have been compared with the corresponding endpoints of the target substance introduced in this dossier and are consider to be similar and therefore support the read-across hypothesis.
On the other hand, the International Joint FAO/WHO Expert Committee on Food Additives (JECFA) has evaluated alicyclic ketones, secondary alcohols and related esters, including the referred 2,6 -dimethyl-4 -heptanol from the group under review and its metabolite 2,6 -dimethylheptan-4 -one (JECFA, 1999). These materials were judged by this Committee not to present a safety concern at the current estimated intake levels. In addition, 2,6 -dimethyl-4 -heptanol is listed as food additives (FDA, 2007).
As conclusion, considering the similarity of the substances referred to the target substance, the quality of the data included (in all cases peer-reviewed), the consistency of the results (in all cases LD50 is clearly above >2000 mg/kg bw), the common metabolic pathways expected, the similar physico-chemical properties, we consider sufficient information is available to allow us for a conclusion on acute oral toxicity endpoint and that no further testing on vertebrate animals is needed and should be avoided.
Justification for selection of acute toxicity – oral endpoint
Although there isn't one key study which individually can be regarded to qualify as key study, sufficient information is available to allow a weight of evidence analysis. This particular study has been chosen as part of this approach considering the structural similarity and common functional groups between the substance tested and the substance target of this registration
Justification for classification or non-classification
In all the studies the oral LD50 was assessed to be > 2000 mg/kg bw. Therefore, according to Directive 67/548 EEC as well as GHS Regulation EC No 1272/2008, 3,6 -dimethylheptan-2 -ol does not need to be classified or labelled on acute oral toxicity.
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