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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Repeated dose toxicity: oral

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Administrative data

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.

Data source

Reference
Reference Type:
other: read-across
Title:
Unnamed
Year:
2011

Materials and methods

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

Test material

Constituent 1
Reference substance name:
1,3,8-trihydroxy-6-methylanthraquinone
EC Number:
208-258-8
EC Name:
1,3,8-trihydroxy-6-methylanthraquinone
Cas Number:
518-82-1
IUPAC Name:
1,3,8-trihydroxy-6-methyl-9,10-anthraquinone
Details on test material:
- Name of test material (as cited in study report): Emodin
- Molecular formula (if other than submission substance): C15H10O5
- Molecular weight (if other than submission substance): 270.23 g/mol
- Smiles notation (if other than submission substance): c12c(C(c3cc(O)cc(c3C1=O)O)=O)cc(C)cc2O
- InChl (if other than submission substance): InChI=1/C15H10O5/c1-6-2-8-12(10(17)3-6)15(20)13-9(14(8)19)4-7(16)5-11(13)18/h2-5,16-18H,1H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Effect levels

open allclose all
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

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

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).

 

Applicant's summary and conclusion

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)