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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 202-589-1 | CAS number: 97-53-0
- 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
Description of key information
Weight-of-evidence NOAEL = 300 mg/kg bw/d (Chronic study, rats, Rel.2)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
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
The repeated dose toxicity of Eugenol was investigated across several key studies performed to assess Eugenol potential for carcinogenicity and for toxicity to reproduction (read-across approach using Isoeugenol), in rats and/or mice exposed by oral route.
In a 90-day repeated day toxicity study in rats (used as range-finding for carcinogenicity), a 10% reduced final body weight together with a 12% reduced body weight gain were observed only in male rats administered 12,500 ppm Eugenol (equivalent to 1250 mg/kg bw/d) compared to control males. The authors also reported that no chemically-related gross or histopathological effects were observed among the rats investigated.
In a similar study conducted in mice (used also as range-finding for carcinogenicity), no statistically significant, test article-related effects on mortality, body weight, body weight gain, gross pathology, and histopathology were noted following dietary administration of Eugenol up to 6,000 ppm daily (900 mg/kg bw/d) for 90 days.
In a carcinogenicity study conducted in rats exposed to Eugenol by diet for 104 weeks, up to 15% reduced body weight from weeks 51 to 102 of treatment together with a decreased body weight gain of 10% during the entire study were observed in the highest dose female group (625 mg/kg bw/d). This effect was considered as a slight adverse systemic effect in the absence of any other effect. No change of body weight or body weight gain that could be considered as adverse was observed in males up to 300 mg/kg bw/d. Furthermore, under the experimental conditions described in the study, the NTP panel concluded that there was no evidence of carcinogenicity for Eugenol in male or female rats.
In a similar carcinogenicity study, dietary administration of Eugenol to mice did not result in any statistically significant test article-related changes in mean food consumption and survival. However, transient decreased mean body weight (week 101 and 104) slightly higher to 10% (limit to consider as adverse effect) was observed in high-dose female together with a decreased body weight gain of 21% during the entire study. Furthermore, under the experimental conditions, the weight of evidence indicates that Eugenol is not a carcinogen in mice (See Iuclid §7.7).
In a two-generation study, the supporting substance, Isoeugenol, was administered to rats daily via oral gavage at dose levels of 0, 70, 230 or 700 mg/kg bw/d. Body weight, food consumption, clinical signs, organ weight, gross and microscopic pathology information allowed to assess the repeated dose toxicity potential of Isoeugenol, and by analogy to Eugenol across the generations. Based on an expert judgement a LOAEL for parental toxicity was determined at 70 mg/kg bw/d, based on decreased body weight gains at all dose-levels, although probably linked to the bolus effect due to the type of administration (gavage) considered as worst-case and less realistic than by diet.
In an embryo-foetal development study, the supporting substance Isoeugenol was administered to female rats via oral gavage at dose levels of 0, 250, 500 and 1000 mg/kg bw/d. The LOAEL was reported to be the low dose level of 250 mg/kg bw/d based on a statistically and dose-dependent reduced gestation body weight gain. Other effects in maternal animals included several types of clinical effects at higher doses and lower maternal relative food intake at the highest dose (1000 mg/kg bw/d).
Therefore, the overall no-observed adverse observed effect (NOAEL) and the lowest-observed adverse observed effect (LOAEL) for repeated dose toxicity study determined in the different key studies are summarised in the table 7.5.
Table 7.5: Overall NOAEL and LOAEL for repeated dose toxicity identified across key studies
Study types |
Substance tested |
Species |
Routes of exposure |
NOAEL (mg/kg bw/d) |
LOAEL (mg/kg bw/d) |
Basis |
90-day |
Eugenol |
Rat |
Diet |
Male: 600 Female: 1250 (highest dose) |
Male: 1250 (highest dose) |
Reduced final body weight of 10% and body weight gain of 12% in male rats tested at 1250 mg/kg bw/d compared to controls |
90-day |
Eugenol |
Mouse |
Diet |
Male and female : ≥ 900 |
- |
Highest dose level, no effect |
Carcinogenicity |
Eugenol |
Rat |
Diet |
Female: 300* Male : ≥ 300 (highest dose) |
Females: 625 (highest dose) |
Reduced body weight up to 15% in high dose female group from weeks 51 to 102 of treatment and decreased body weight gain of 10% within the 104 weeks |
Carcinogenicity |
Eugenol |
Mouse |
Diet |
Females: 450 Males: 900 (highest dose) |
Females: 900 (highest dose) |
Reduced body weight gain, considered as adverse effect (>10%) at the highest dose and observed only during the two last weeks of treatment (week 101 and week 104). Transient body weight gain decrease up to 21% within the104 weeks at the highest dose. |
Two generation study |
Isoeugenol |
Rat |
Gavage |
Male and female : 70 (lowest dose) |
Male and female : 230(mid-dose) |
Decreased body weight gains at all dose-levels, although probably linked to the bolus effect due to gavage |
Embryo-fœtal developmental study |
Isoeugenol |
Rat |
Gavage |
Not identified |
Female : 250 (lowest dose) |
Dose-dependent reduced gestation body weight gain |
*Relevant NOAEL determined from expert judgement according to the following criteria.
In a weight of evidence approach, i.e. taking into account the whole database (see Table 7.5), the following criteria were considered to determine the most relevant NOAEL for repeated dose toxicity of Eugenol:
- the substance tested: studies on Eugenol preferred to Isoeugenol, which showed higher irritating potential than Eugenol inducing local effects in animals,
- the duration of the study: long-term studies preferred to short-term studies to detect delayed systemic effect,
- the route of exposure: diet preferred to gavage which induced bolus effects reflecting less realistic conditions
- the effects observed: obvious relevant systemic effects observed with dose-related changes preferred to transient effects inducing equivocal results.
According to these criteria, results from the carcinogenicity study conducted in rats allowed to identify the most relevant NOAEL at 300 mg/kg bw/d for repeated dose toxicity of Eugenol. This value was used to extrapolate the different DNELs for worker and general population.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Weight of evidence approach taking into account the whole database: repeated dose toxicity, reproductive toxicity and carcinogenicity.
Justification for classification or non-classification
No specific target organ toxicity was observed following repeated exposure to Eugenol. As a result, the substance does not meet the criteria for classification as STOT-RE according to Regulation (EC) No 1272/2008, Annex I section 3.9.
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.