Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-219-1 | CAS number: 104-61-0
- 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
Link to relevant study record(s)
Description of key information
By oral exposure, both the aliphatic nonalactone and the ring-opened hydroxycarboxylic acid can be absorbed from the gastrointestinal tract following oral exposure. Therefore, gamma-nonalactone is readily hydrolysed either before absorption or in systemic circulation.
Following dermal exposure to gamma-nonalactone, molecular weight and log Kow (2.5) values are in favour of dermal absorption which however should be limited considering the moderate water solubility of the substance.
Considering the low vapor pressure, exposure by inhalation to gamma-nonalactone is unlikely to occur or is anticipated to be very limited.
In any case, after systemic absorption, gamma-nonalactone is expected to be efficiently metabolized to innocuous products without saturation of the metabolic pathways.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
Ɣ-decalactone, Ɣ-undecalactone and Ɣ-caprolactone data are considered in this dossier in a read across approach to fill-in the endpoints for Ɣ-nonalactone as demonstrated in the overall justification of the read across presented in section 13.
The forty-ninth joint FAO/WHO Expert Committee on Food Additives (JECFA) evaluated a group of aliphatic lactones used as flavouring substances in food (1998). The majority of the aliphatic lactones have been reported to occur naturally in traditional foods and Ɣ-decalactone is one of the four aliphatic lactones having the highest usage as flavouring substances. It is also ubiquitous in food occurring mainly in fruits, berries, alcoholic beverages, meats and dairy products. JECFA evaluation of all the data indicated no safety concern associated with intake of Ɣ-nonalactone, Ɣ-decalactone, Ɣ-undelactone and Ɣ-caprolactone (JECFA, 1998). Ɣ-nonalactone and Ɣ-undecalactone have been evaluated previously at the Eleventh Meeting of the Committee and an ADI of 1.25 mg/kg b.w. was established for each substance.
The following table indicated the physico-chemical and toxicological data which have been identified in the scope of REACH dossiers and considered as relevant for Ɣ-nonalactone toxicokinetics.
Table 7.1: Relevant data for lactone toxicokinetics
Properties |
Ɣ-Caprolactone |
Ɣ-Nonalactone |
Ɣ-Decalactone |
Ɣ-Undecalactone |
CAS |
695-06-7 |
104-61-0 |
706-14-9 |
104-67-6 |
Molecular mass |
114.14 g/mol |
156.23 g/mol |
170.25 g/mol |
184.28 g/mol |
Log Kow at 25°C |
0.83 |
2.5 |
3 |
3.6 |
Water solubility |
Soluble 5263 mg/L (extrapolated) |
Soluble 2200 mg/L |
Soluble 1179 mg/L (interpolated) |
Moderately soluble 158 mg/L |
Vapour pressure |
4.2 Pa |
1.9 Pa |
0.72 Pa |
0.27 Pa |
Available reliable toxicological studies |
||||
Acute toxicity LD50 |
Oral: >2000 mg/kg bw Dermal: n.d. |
Oral: 6500 mg/kg bw Dermal: >5000 mg/kg bw |
Oral: n.d. Dermal: n.d. |
Oral: n.d. Dermal: > 2000 mg/kg bw |
Irritation |
Not skin irritating up to 20% Irritation to eyes: n.d. |
Not skin irritating Not irritating to eyes |
n.d. |
Skin irritation: n.d. Irritation to eyes: n.d. |
Sensitisation |
Not sensitizing (GPMT) |
Not sensitizing in human |
n.d. |
Not sensitizing (OET) |
Mutagenicity |
Ames test: negative MLA: n.d. In vitro cytogenicity: negative |
Ames test: n.d. MLA: negative In vitro cytogenicity: n.d. In vivo micronucleus: negative |
Ames test: negative MLA: n.d. In vitro cytogenicity: n.d. |
Ames test: negative MLA: n.d. In vitro cytogenicity: n.d. |
Repeated dose toxicity |
NOAEL = 1000 mg/kg bw/d (28-day toxicity study) |
n.d. |
n.d. |
n.d. |
Toxicity to reproduction |
NOAEL = 1000 mg/kg bw/d (pre-developmental toxicity study) |
n.d. |
n.d. |
n.d. |
n.d.: no data
The toxicokinetic profile of lactones is not determined of absorption, distribution, metabolism or excretion measurements even if a few studies considered as not reliable existed. Rather, the overall physical chemical properties of the lactones, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from mutagenicity assays were used to predict the toxicokinetic behavior. Ɣ-nonalactone, Ɣ-decalactone and Ɣ-undecalactone are structurally similar compounds of aliphatic lactones as justified in section 13. They are formed by acid-catalysed intramolecular cyclization of 4-carbon hydroxycarboxylic acids to yield five-(gamma-) membered lactone rings. The stability of the lactone ring in an aqueous environment is pH-dependent since a pH-equilibrium is established between the open-chain hydroxycarboxylic acid and the lactone ring.
Toxicokinetics, distribution and excretion by oral route:
Incubation of γ-nonalactone and γ-undecalactone with rat liver homogenate in buffer solution at pH 7.5 resulted in 62–94% and 26–40% hydrolysis within 1 h, respectively. After 1 h, 81–88% and 45–70% hydrolysis of γ-nonalactone and γ-undecalactone, respectively, occurred at pH 8.0 (Morgareidge, 1963). Therefore, it is anticipated that in acidic media, such as stomach (or urine), the Ɣ-nonalactone ring is favoured while in basic media, such as intestines (or blood), the open-chain hydroxycarboxylate anion is favoured. Both the aliphatic lactones and the ring-opened hydroxycarboxylic acids can be absorbed from the gastrointestinal tract following oral exposure. Therefore, Ɣ-nonalactone is readily hydrolysed either before absorption or in systemic circulation. Then linear saturated 4-hydroxycarboxylic acids are converted, via acetyl coenzyme A, to alpha-hydroxythioesters which then undergo alpha-oxidation and alpha-decarboxylation to yield an acetyl CoA fragment and a new alpha-hydroxythioester reduced by 2 carbons. Even-numbered carbon acids continue to be oxidized and cleaved to yield metabolites that are completely metabolized in the citric acid cycle and excreted from the body as CO2, glucuronic acid or sulfate conjugates in the urine and, to a lesser extent, in the faeces. Therefore, Ɣ-nonalactone is expected to be efficiently metabolized to innocuous products without saturation of the metabolic pathways.
Toxicokinetics, distribution and excretion by dermal route:
Following dermal exposure to Ɣ-nonalactone, molecular weight and log Kow (2.5) values are in favour of dermal absorption which however should be limited considering the water solubility of the substance. This is corroborated by the in vitro dermal absorption study performed on porcine ear skin exposed to Ɣ-caprolactone which did not penetrate the skin in detectable amounts (Wallny, 2002) whereas Ɣ-caprolactone is considered as dermal absorption worst-case for the linear saturated 4-hydroxycarboxylic acid derived-lactones based on its physico-chemical properties. However, it is likely Ɣ-nonalactone will be distributed as ring-opened hydroxycarboxylic acid in blood if very low amounts are dermal absorbed, then metabolized to innocuous metabolites which may be conjugated in order to be excreted mainly in urine.Moreover, in the absence of skin irritation, no damage to the skin surface should occur which may enhance penetration.
Toxicokinetics, distribution and excretion by inhalation:
Considering the low vapor pressure, exposure by inhalation to Ɣ-nonalactone is unlikely to occur or is anticipated to be very limited. In this last case, as potential absorption following ingestion is expected (see above), it is likely Ɣ-nonalactone will also be absorbed if it is inhaled, distributed as ring-opened hydroxycarboxylic acid, metabolized to innocuous metabolites which may be conjugated in order to be excreted mainly in urine.
References:
- Cramer G.M., Ford, R.A. & Hall, R.L. (1978) Estimation of toxic hazard
- A decision tree approach. Food Cosmet.Toxicol., 16, 255–276. -JECFA (1998) Aliphatic lactones. WHO food additives series 40.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.