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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Reproductive toxicity study

Based on the data available from different studies, NOAEL for test material was considered to be 1000mg/kg /day for reproductive toxicity, when male and female rats were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.

Link to relevant study records
Reference
Endpoint:
multi-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Experimental data from study report
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
A multigeneration reproduction study was conducted in rats administered the dye in their diets at concentrations based on multiples of lx, 10x, 30x, and 100x the ADI (acceptable daily intake).
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available
Specific details on test material used for the study:
- Name of test material (IUPAC name): 1,4-Bis(p-tolylamino)anthraquinone
- Common name: C.I. Solvent Green 3
- Molecular formula: C28H22N2O2
- Molecular weight: 418.4938 g/mol
- Smiles notation: c12c(c(Nc3ccc(cc3)C)ccc1Nc1ccc(cc1)C)C(=O)c1c(C2=O)cccc1
- InChl: 1S/C28H22N2O2/c1-17-7-11-19(12-8-17)29-23-15-16-24(30-20-13-9-18(2)10-14-20)26-25(23)27(31)21-5-3-4-6-22(21)28(26)32/h3-16,29-30H,1-2H3
- Substance type: Organic

Species:
rat
Strain:
not specified
Details on species / strain selection:
No data available
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data available
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:Test chemical were administrated in a diet based on acceptable daily intake.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Diet
- Concentration in vehicle: 1x, 10x, 30x and 100x the ADI (acceptable daily intake)
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
up to 3 generation
Frequency of treatment:
Daily
Details on study schedule:
No data available
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Positive control:
No data available
Parental animals: Observations and examinations:
No data available
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
No data available
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No adverse effects on reproduction were observed.
Remarks on result:
other: Generation: multigeneration
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Generation:
F1
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Conclusions:
In a multigeneration reproduction study the NOAEL was considered to be 1,000 mg/kg when rats were treated with test chemical orally.
Executive summary:

A multigeneration reproduction study was conducted in rats administered the test chemical in their diets at concentrations based on multiples of lx, 10x, 30x, and 100x the ADI (acceptable daily intake); the doses, however, did not exceed 1,000 mg/kg (Pierce et al. 1974). No adverse effects on reproduction were observed.Therefore, NOAEL was considered to be 1,000 mg/kg when rats were treated with test chemical orally.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Data is Klimicsh 2 and from authoritative database
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity study

Data available from different studies were reviewed to determine the reproductive toxicity of testchemical.The studies are as mentioned below:

Study 1

A multigeneration reproduction study was conducted in rats administered the test chemical in their diets at concentrations based on multiples of lx, 10x, 30x, and 100x the ADI (acceptable daily intake); the doses, however, did not exceed 1,000 mg/kg (Pierce et al. 1974). No adverse effects on reproduction were observed.Therefore, NOAEL was considered to be 1,000 mg/kg when rats were treated with test chemical orally.

Study 2

Reproductive toxicity study was observed for test material in P0 female Wistar rats, when they were  exposed at the concentration of 0, 94, 282 or 940mg /kg bw/day through  6-17of gestation period by oral (gavage).The test substance (in1%carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage. Dams were observed daily for clinical signs, body weight and food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half of the foetuses were also examined for soft tissue anomalies where as remaining foetuses were examined for skeletal anomalies following alizarin red staining. At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.

At the dose group of 282 and 940 mg /kg bw/day two Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered by the study authors to be incidental as a dose relation was missing.No mortality was observed. Discoloured faeces were observed at 940mg/kg bw/day. No significant changes were observed on litter parameters and fetal weight. No significant changes were observed on external soft tissue and skeletal anomalies in treated group compare to control. Therefore NOAEL was considered to be 940 mg /kg bw/day for test material in P0 female Wistar rats.

Study 3

Reproductive and development toxicity study of  test materialwas performed on female  HanBrl:WIST (SPF) rats.22 mated females rats were divided into per dose group . The test substance in bi-distilled water containing 1% carboxymethylcellulose was given daily at dose volumes of 10 ml/kg bw by oral gavagein dose0, 100, 300 and 1000 mg/kg bw/day (0, 86, 258, and 861 mg active dye/kg bw/day) from day 6 (implantation) through to day 20post coitum. Mortality, morbidity, signs of abortion, and clinical signs and/or symptoms was checked at least twice daily. Food consumption was recorded on 3-day intervals and body weights were recorded daily. The females were sacrificed on gestation day 21, subjected to macroscopic examination. The foetuses were removed by Caesarean section, sexed, weighed, examined for gross external abnormalities, killed, and allocated to either visceral or skeletal (about one half of the foetuses for each examination).

No mortalities occurred. Clinical signs included darker faeces (all treated groups, from day 7-21 post coitum), and discolouration of skin, eyes and bedding (generally only in the high dose group). The mean body weight gain was slightly decreased and the corrected body weight gain (corrected for gravid uterus weight) was marginally lower in high-dose females compared to control females. Food consumption was similar in treated and control groups. One low-dose female was not pregnant. The incidence of pre-implantation loss was slightly higher (statistically significant) in the high-dose group; this difference was considered as being incidental by the study authors because pre-implantation loss mainly occurred prior to onset of treatment. Post-implantation loss and number of foetuses per dam was not affected. At necropsy discolouration of intestinal contents, kidneys, fatty tissues, intrauterine fluids and foetuses was noted in all high-dose dams. No effects on litter parameters or foetal weight were observed. Incidences of external, visceral and skeletal findings were similar for control and treated groups. Hence No Observed Adverse Effect Level (NOAEL) for maternal toxicity is 300 mg/kg bw/day (258 mg active dye/kg bw/day) and the NOAEL for reproductive and developmental toxicity is 1000 mg/kg bw/day (861 mg active dye/kg bw/day).When femaleHanBrl:WIST (SPF)rats were treated with test material orally.

Based on the data available from different studies, NOAEL for test material was considered to be 1000mg/kg /day for reproductive toxicity, when male and female rats were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.

Effects on developmental toxicity

Description of key information

Developmental toxicity study

Based on the various studies available for the test chemical were reviewed to determine the developmental toxicity, NOAELfor test chemical was considered to be 1000 mg /kg bw/day .When rats were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive and developmental toxicant.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Experimental data from study report
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Test chemical was tested for teratogenic effects in rats.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report):Solvent Green 3 (D 6 C Green No.6)
- Molecular formula:C28H22N2O2
- Molecular weight :418.4938 g/mole
- Substance type:Organic
- Physical state:No data available
- Impurities (identity and concentrations):No data available
Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data available
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Test chemical were administrated in a diet based on acceptable daily intake.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Diet
- Concentration in vehicle: 1x, 10x, 30x and 100x the ADI (acceptable daily intake)

Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Any other deviations from standard protocol: Animals were dosed during the critical stage of organogenesis.
Duration of treatment / exposure:
No data available
Frequency of treatment:
Daily
Duration of test:
Long term
Dose / conc.:
1 000 other: mg/kg/day
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Maternal examinations:
Reproductive effects were examined.
Ovaries and uterine content:
No data
Fetal examinations:
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effects were observed on reproduction of treated rats.
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No effects were observed on reproduction of treated rats.
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No effects were observed on reproduction of treated rats.
Abnormalities:
not specified
Localisation:
not specified
Fetal body weight changes:
not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No effect were observed on skeleton or soft tissues of treated pups.
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
external malformations
skeletal malformations
visceral malformations
Remarks on result:
other: No effect were observed on skeleton or soft tissues of treated pups.
Abnormalities:
not specified
Developmental effects observed:
not specified
Treatment related:
not specified
Conclusions:
The NOAEL was considered to be 1000 mg/kg/day when rats were treated with test chemical orally.
Executive summary:

In a multigeneration reproduction toxicity study, rats were treated with test chemical in the concentration based on multiples of 1x, 10x, 30x and 100x the ADI (acceptable daily intake) which did not exceed 1,000 mg/kg in diet. No effects were observed on reprodution of F0 genration in treated rats. In addition, no effects were observed on skeleton or soft tissues of treated pups. Therefore, NOAEL was considered to be 1000 mg/kg/day when rats were treated with test chemical orally for long term.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Data is Klimicsh 2 and from authoritative database
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Developmental toxicity study

Data available from different studies for test chemicals were reviewed to determine the developmental toxicity of test chemical. The studies are as mentioned below:

Study 1

In a multigeneration reproduction toxicity study, rats were treated with test chemical in the concentration based on multiples of 1x, 10x, 30x and 100x the ADI (acceptable daily intake) which did not exceed 1,000 mg/kg in diet. No effects were observed on reprodution of F0 genration in treated rats. In addition, no effects were observed on skeleton or soft tissues of treated pups. Therefore, NOAEL was considered to be 1000 mg/kg/day when rats were treated with test chemical orally for long term.

Study 2

The development toxicity study of  test chemicalwas performed on female  HanBrl:WIST (SPF) rats.22 mated females rats were divided into per dose group . The test chemical in bi-distilled water containing 1% carboxymethylcellulose was given daily at dose volumes of 10 ml/kg bw by oral gavagein dose0, 100, 300 and 1000 mg/kg bw/day (0, 86, 258, and 861 mg active dye/kg bw/day) from day 6 (implantation) through to day 20post coitum. Mortality, morbidity, signs of abortion, and clinical signs and/or symptoms was checked at least twice daily. Food consumption was recorded on 3-day intervals and body weights were recorded daily. The females were sacrificed on gestation day 21, subjected to macroscopic examination. The foetuses were removed by Caesarean section, sexed, weighed, examined for gross external abnormalities, killed, and allocated to either visceral or skeletal (about one half of the foetuses for each examination).

No mortalities occurred. Clinical signs included darker faeces (all treated groups, from day 7-21 post coitum), and discolouration of skin, eyes and bedding (generally only in the high dose group). The mean body weight gain was slightly decreased and the corrected body weight gain (corrected for gravid uterus weight) was marginally lower in high-dose females compared to control females. Food consumption was similar in treated and control groups. One low-dose female was not pregnant. The incidence of pre-implantation loss was slightly higher (statistically significant) in the high-dose group; this difference was considered as being incidental by the study authors because pre-implantation loss mainly occurred prior to onset of treatment. Post-implantation loss and number of foetuses per dam was not affected. At necropsy discolouration of intestinal contents, kidneys, fatty tissues, intrauterine fluids and foetuses was noted in all high-dose dams. No effects on litter parameters or foetal weight were observed. Incidences of external, visceral and skeletal findings were similar for control and treated groups. Hence the No Observed Adverse Effect Level (NOAEL) for developmental toxicity was considered to be 1000 mg/kg bw/day (861 mg active dye/kg bw/day).When femaleHanBrl:WIST (SPF)rats were treated with test chemicalorally.

 

Study 3

Developmental toxicity study was observed for test chemical in P0 female Wistar rats ,they were were exposed at the concentration of 0, 94, 282 or 940mg /kg bw/day through  6-17of gestation period by oral (gavage).The test substance (in1%carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage.Dams were observed daily for clinical signs ,body weight and food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses weresexed, weighed and submitted to external examination. About one half of the foetuses werealso examined for soft tissue anomalies whereas remaining foetuses were examined forskeletal anomalies following alizarin red staining.At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.

 At the dose group of 282 and 940 mg /kg bw/day twoFemales were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. No mortality was observed. Discoloured faeces were observed at 940mg/kg bw/day. No significant changes were observed on litter parameters and fetal weight. No significant changes were observed on external soft tissue and skeletal anomalies in treated group compare to control. Therefore NOAEL for developmental toxicity was considered to be  1000(940)mg /kg bw/day . When femaleWistar ratswere treated with test chemicalthrough6-17of gestation period by oral (gavage).

 

Based on the various studies available for the test chemical were reviewed to determine the developmental toxicity, NOAELfor test chemical was considered to be 1000 mg /kg bw/day .When rats were treated with test chemical orally. Thus, comparing this value with the criteria ofCLP regulation testchemical isnot likelyto classify as reproductive and developmental toxicant.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation test chemical isnot likelyt o classify as reproductive and developmental toxicant.

Additional information