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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 201-549-0 | CAS number: 84-65-1
- 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
Key study: Read-across from experimental data on the analogue CAS No.518-82-1. Test method equivalent to OECD guideline 408. GLP study.
90-day oral toxicity study:
Rats:
NOAEL 62 mg/kg bw/day male (based on decreased body weights)
NOAEL 31 mg/kg bw/day female (based on decreased body weights)
Mice:
NOAEL 147 mg/kg bw/day male (based on decreased body weights)
NOAEL > 848 mg/kg bw/day female (based on decreased body weights)
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral
- Remarks:
- other: read-across from a study with an analogue
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The analogue CAS nº 518-82-1 emodin shares the same functional group with the substance CAS nº 84-65-1 anthraquinone and the results can be extrapolated to anthraquinone.
- Principles of method if other than guideline:
- Read-across approach from a study on the analogue CAS nº 518-82-1 emodin.
- GLP compliance:
- yes
- Dose descriptor:
- NOAEL
- Effect level:
- 62 other: mg/kh bw/day
- Sex:
- male
- Basis for effect level:
- other: Rats
- Dose descriptor:
- NOAEL
- Effect level:
- 31 other: mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: Rats
- Dose descriptor:
- NOAEL
- Effect level:
- 147 other: mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: Mice
- Dose descriptor:
- NOAEL
- Effect level:
- > 848 other: mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: Mice
- Critical effects observed:
- not specified
- Conclusions:
- Rats:
NOAEL 62 mg/kg bw/day male (based on decreased body weights)
NOAEL 31 mg/kg bw/day female (based on decreased body weights)
Mice:
NOAEL 147 mg/kg bw/day male (based on decreased body weights)
NOAEL > 848 mg/kg bw/day female (based on decreased body weights) - Executive summary:
Based on the experimental results obtained with the analogue emodin, the read-across approach is applied and the results can be extrapolated to substance anthraquinone under test conditions.
Rats:
NOAEL 62 mg/kg bw/day male (based on decreased body weights)
NOAEL 31 mg/kg bw/day female (based on decreased body weights)
Mice:
NOAEL 147 mg/kg bw/day male (based on decreased body weights)
NOAEL > 848 mg/kg bw/day female (based on decreased body weights)
Reference
Based on the experimental results obtained with the analogue emodin, the read-across approach is applied and the results can be extrapolated to substance anthraquinone under test conditions.
The analogue emodin shares the same functional group with anthraquinone and also has comparable values for the relevant molecular properties. These properties are:
- a high log Pow value which is 3.39 for anthraquinone and 4.01 for emodin,
- a low water solubility (both substances are insoluble in water) and
- similar molecular weights which are 208.22 for anthraquinone and 270.23 for emodin.
As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 1.1.0 (see attachement).
Table 1: Data Matrix, Analogue Approach
CAS Number
|
518-82-1 |
84-65-1 |
|
CHEMICAL NAME
|
Analogue 1 Emodin |
Anthraquinone |
|
PHYSICO-CHEMICAL DATA |
|||
Melting Point |
Experimental results: 256-257 °C |
Experimental results: 286 ºC |
|
Boiling Point |
Estimated data: The calculated boiling point is 479.69 ºC (EPI Suite, MPBPVP v1.43) |
Experimental results: 377 ºC |
|
Density |
No data |
Experimental results: 1.42-1.44 |
|
Vapour Pressure |
Estimated data: The calculated vapour pressure is 8.91E-010 Pa at 25 ºC (EPI Suite, MPBPWIN v1.43).
|
Weight of evidence: The calculated vapour pressure is 5.1E-006 Pa at 25 ºC (EPI Suite, MPBPWIN v1.43). The experimental vapour pressure of the substance is 1.16X10-7 mm Hg at 25 ºC (peer reviewed publication). |
|
Partition Coefficient (log Kow) |
Estimated data: The calculated partition coefficient is(EPI Suite, KOWWIN v1.68 estimate).
|
Weight of evidence: The calculated partition coefficient is(EPI Suite, KOWWIN v1.68 estimate). The experimental partition coefficient octanol-water of the substance is 3.39 (peer reviewed publication). |
|
Water solubility
|
Practically insoluble in water.
|
Experimental results: 0.17 mg/L at 20 ºC
|
|
ENVIRONMENTAL FATE and PATHWAY |
|||
Aerobic Biodegradation
|
Estimated data: No readily biodegradable (BIOWIN v4.10)
|
Weight of evidence: Based on available experimental data from bibliography the substance is considered as readily biodegradable. |
|
Anaerobic Biodegradation |
No data
|
No data |
|
ENVIRONMENTAL TOXICITY |
|||
Acute Toxicity to Fish |
No data (insoluble in water)
|
No data (insoluble in water)
|
|
Acute Toxicity to Aquatic Invertebrates |
No data (insoluble in water) |
No data (insoluble in water)
|
|
Toxicity to Aquatic Plants
|
No data (insoluble in water) |
No data (insoluble in water) |
|
Toxicity to soil macroorganisms
|
Experimental results:Eisenia fetida 56-d LC50 > 512 mg/kg soil dw (mortality) 56-d EC50 = 182 mg/kg soil dw (the test substance significantly inhibited reproduction). |
Read-across from emodin: 56-d LC50 > 394 mg/kg soil dw (based on mortality) 56-d EC50 = 140 mg/kg soil dw (based on effects on reproduction) |
|
Toxicity to birds |
No data.
|
Experimental results: LC50 > 5000 ppm |
|
MAMMALIAN TOXICITY |
|||
Acute Oral |
No data |
Experimental results: LD50 > 2000 mg/kg bw |
|
Acute Inhalation |
No data |
No data |
|
Acute Dermal |
No data |
Experimental results: LD50 ≥ 3000 mg/kg bw |
|
Skin irritation / Eye irritation |
No data |
Experimental results: Not irritating |
|
Skin sensitisation |
No data |
Experimental results: Sensitising |
|
Repeated Dose |
Repeated dose toxicity: oral: Key study: 14 weeks in rats: NOAEL 80 mg/kg bw/day male (based on decreased body weights) NOAEL 40 mg/kg bw/day female (based on decreased body weights)
Repeated dose toxicity: oral: Key study: 14 weeks in mice: NOAEL 190 mg/kg bw/day male (based on decreased body weights)
NOAEL > 1100 mg/kg bw/day female (based on decreased body weights) |
Read-across from emodin: Rats: NOAEL 62 mg/kg bw/day male (based on decreased body weights) NOAEL 31 mg/kg bw/day female (based on decreased body weights)
Mice: NOAEL 147 mg/kg bw/day male (based on decreased body weights)
NOAEL > 848 mg/kg bw/day female (based on decreased body weights)
|
|
Genetic Toxicity in vitro
|
Gene mutation in bacteria
|
Key study: Positive for TA100 in the presence of S9 activation; negative for TA98, with or without S9.
|
1.- Key study: The substance AQ-FC did not show any mutagenic activity either with or without metabolic activation in thetester strains (S. typhimurium TA1535, TA1537, TA98 and TA100 or in E. coli WP2uvrA).
2.- Key study: The substance anthraquinone (100% pure) did not show any mutagenic activity either with or without metabolic activation in theAmestester strains used (S. typhimurium TA98, TA100 and TA102).
3.- Key study: The substance anthraquinone (Friedel-Crafts process) did not show any mutagenic activity either with or without metabolic activation in thetester strains used (TA98 and TA100).
|
Chromosomal aberration
|
1.- Key study: Chromosome aberrations were induced in cultured CHO cells in the absence of S9 activation and in the presence of S9; the response observed without S9 was stronger than with S9.
2.- Key study: Mammalian cell micronucleus test: The test substance did not reveal any micronuclei inducing activity in either human lymphocytes or in Hep-G2.
|
Read-across from emodin:Contradictory results from different sources. Data available from in vivo studies. |
|
Mammalian gene mutation
|
1.- Key study: The substance induced a moderate increase in mutant fraction (only tested without metabolic activation).
2.- Key study: The test substance did not result in an increase in the number of colonies resistant to 6 -TG. Exposure in suspension in the presence of liver homogenate was also negative.
3.- Key study: The test substance emodin was highly mutagenic without metabolic activation. However, the increase in the induction of mutation was observed at highly toxic concentrations.
|
Read-across from emodin:Negative. |
|
Genetic Toxicity in vivo
|
Mammalian erythrocyte Micronucleus test: 1.- Key study: There was no statistically significant enhancement in the frequency of micronucleated PCEs in comparison to the negative controls at both preparation intervals.
2.- Key study: In peripheral blood samples from mice in the 14-week feed study, an increase in the frequency of micronucleated NCEs was seen in females, but not in males. The result in female mice was concluded to be weakly positive.
Mammalian bone marrow chromosome aberration test: 1.- Key study: No increases in the frequencies of micronucleated erythrocytes were observed in any of the treatment groups (only males were used).
2.- Key study: No increases in the frequencies of micronucleated erythrocytes were observed in any of the treatment groups (males and females were used).
|
Read-across from emodin: Negative |
|
Carcinogenicity
|
Key study: No carcinogenic activity.
There was no evidence of carcinogenic activity of emodin in male rats. There was equivocal evidence of carcinogenic activity in female rats.
There was equivocal evidence of carcinogenic activity in male mice. There was no evidence of carcinogenic activity in female mice.
|
Read-across from emodin: No carcinogenic activity. |
|
Reproductive Toxicity: developmental toxicity |
Key study:
NOAEL rats maternal: 57 mg/kg/day (based on maternal body weight and weight gain) NOAEL rats foetal: 80-144 mg/kg/day (highest dose)
NOAEL mice (maternal and foetal): 391 mg/kg/day LOAEL 1005 mg/kg/day (decreased maternal body weight and weight gain decreased foetal body weight).
|
Read-across from emodin: NOAEL rats maternal: 44 mg/kg/day (based on maternal body weight and weight gain) NOAEL rats foetal: 62-111 mg/kg/day (highest dose)
NOAEL mice (maternal and foetal): 301 mg/kg/day LOAEL 774 mg/kg/day (decreased maternal body weight and weight gain decreased foetal body weight).
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 31 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Klimisch 2. Read-across approach: The study was performed according to NTP (National Toxicology Program, within the U.S. Department of Health and Human Services) standard protocol. Equivalent to OECD 408. GLP study.
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
Key study: Read-across from experimental data on the analogue CAS No.518-82-1. Test method equivalent to OECD guideline 408. GLP study.
90-day oral toxicity study:
Rats:
NOAEL 62 mg/kg bw/day male (based on decreased body weights)
NOAEL 31 mg/kg bw/day female (based on decreased body weights)
Mice:
NOAEL 147 mg/kg bw/day male (based on decreased body weights)
NOAEL > 848 mg/kg bw/day female (based on decreased body weights)
The occurrence and severity of spontaneous chronic progressive nephropathy (CPN) in control male F344 rats as well as the frequency of treatment-related CPN exacerbation were histopathologically reevaluated. A series of 43 National Toxicology Program (NTP) 90-day toxicity studies comparing the influence of NIH-07 or NTP-2000 diets was examined. Relationships between the histopathologic findings at 90 days and renal tubule proliferative lesions recorded in subsequent 2-year bioassays for 24 chemicals were statistically analyzed. CPN lesions were observed in 100% of the control male rats regardless of diet, but CPN was more severe in control rats fed NIH-07. Approximately one-third of the 90-day studies demonstrated a treatment-related exacerbation of CPN severity, which was independent of diet. For chemicals that proceeded to 2-year bioassays, all studies with a statistically significant increase in renal tubule tumors (RTT)at 2-years had treatment-related exacerbation of CPN in the 90-day and 2-year studies. These findings indicate that CPN occurs ubiquitously in young male F344 rats and that treatment-related exacerbation of CPN in 90-day studies is a relatively common occurrence, having the potential to be predictive of an increased incidence of RTT in subsequent 2-year bioassays (Travlos GS,Hard GC,Betz LJ,Kissling GE,Toxicol Pathol.2011 Feb; 39(2):381-9).
Chronic progressive nephropathy (CPN) is a rodent-specific, age-related renal disease, particularly of male rats, characterized by a spectrum of distinct histological changes which may begin early in the animal's life and progress to end-stage renal disease in certain rat strains. Although CPN-related pathology is well known to most toxicological pathologists other features of CPN such as pathogenesis, modulating factors, proliferative nature, response to chemical exposure and relationship to tumorigenesis are less clearly acknowledged. CPN is generally regarded as a degenerative to atrophic disease with compensatory regenerative hyperplasia. The proliferative nature of CPN often becomes problematic in advanced to end-stage renal disease. At this stage, a number of tubule profiles may be mistaken for atypical tubule hyperplasia, the reported precursor lesion of tubule adenoma. CPN associated proliferative tubule profiles must be carefully separated from atypical tubule hyperplasia particularly in studies where chemical exposure has exacerbated CPN. Over the past several years increasing evidence has supported the hypothesis that CPN may be regarded as a type of "mode of action" during renal carcinogenesis in rodent bioassay studies. Retrospective studies of control and treated animals have consistently shown a relationship between the increased severity of CPN and the presence of atypical tubule hyperplasia and small, incipient renal adenomas. Understanding CPN-related tumorigenesis is important for human risk assessment interpretation. Since CPN is a rodent specific disease with no apparent similar human kidney disease condition, evidence that renal tumors may arise from an interaction with CPN could assist regulatory agencies in interpreting data from studies with exacerbated CPN (John Curtis Seely and Gordon C. Hard, Journal of Toxicologic Pathology, Vol. 21 (2008), No. 4 pp. 199).
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study with the longest duration (90 days) and lowest NOAEL was chosen as key study.
Justification for classification or non-classification
Based on the available information from 90 -day oral toxicity studies in rats and mice conducted with the analogue emodin, the only effect observed was a decrease on body weights. Based on this information, the substance anthraquinone is not classified for Specific target organ toxicity — repeated exposure since these effects are considered not to support classification.
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.