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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18-07-1986 to 15-08-1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males - 126 g (115-137 g), females - 115 g (108-128 g)
- Housing: in Makrolon-Kafigen Type II cages
- Diet (e.g. ad libitum): Altromin 1324 pellets
- Water (e.g. ad libitum): ad libitum

DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 50%
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: 18-07-1986 to 15-08-1986
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Due to the good dispersibility of reactive blue FC 05717 in water in the concentration range used, a homogeneous distribution of the test suspension was obtained in the formulations. The test substance was administered to the rats via oral gavage. The test substance suspension was found to be stable for 48 h once prepared.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
All the test concentrations were analytically verified at least once during the study.
Duration of treatment / exposure:
28 d
Frequency of treatment:
Daily
Dose / conc.:
40 mg/kg bw/day (nominal)
Dose / conc.:
200 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
six rats per sex per dose
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
The animals were regularly observed, weighed and the feed intake determined.
Sacrifice and pathology:
At the end of treatment, hematological and clinical-chemical investigations were carried out as well as organ weights (testes, liver, kidneys, adrenal glands). Heart, testes, liver, lung, spleen, kidney, adrenal, and other macroscopically abnormally altered organs/tissues were histopathologically examined.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
The relative liver weight in 1000 mg/kg/day females were significantly increased compared to controls. Although the absolute liver weight in these females were also elevated but there was no statistical significance.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
All animals at 1000 mg/kg/day presented a blue coloration of the visible connective tissue, particularly in the skin area, dark blue kidneys and bluish gastrointestinal contents. Also, in the females of the highest dose, approximately 10% higher liver weight was observed which was interpreted by the authors as a sign of a non-specific adaptation due to increased metabolic activity.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no treatment-related systemic effects observed
Key result
Critical effects observed:
no
Conclusions:
Under the study conditions, the systemic NOAEL of the test substance in rats was considered to be 1000 mg/kg/day.
Executive summary:

A study was conducted to determine the oral repeated dose toxicity of the test substance in rats according to OECD Guideline 407 and EU method B.7, in compliance with GLP. Male and female Wistar rats (6/sex/dose) were administered the following concentrations via oral gavage (suspended in water, at a constant volume of 10 mL/kg): 0, 40, 200 and 1000 mg/kg bw/day. Mortality, clinical signs, body weight and food consumption were recorded daily. At necropsy, blood samples were collected for haematology and clinical chemistry investigations. Also, a gross macroscopical examination was conducted, and organs were weighed. Routine histopathological examination was performed on the major organs such as heart, liver, kidneys, testes, adrenals, spleen, lungs etc. No treatment-related clinical signs of toxicity were observed. There were no treatment-related adverse effects on the body weight, food consumption, hematological and clinical biochemistry examinations. All animals at 1000 mg/kg bw/day presented a blue coloration of the visible connective tissue, particularly in the skin area, dark blue kidneys and bluish gastrointestinal contents. This was attributed to the inherent colour of the test substance. Also, in the females of the highest dose, approximately 10% higher liver weight was observed which was interpreted by the authors as a sign of a non-specific adaptation due to increased metabolic activity. Under the study conditions, the systemic NOAEL of the test substance in rats was considered to be 1000 mg/kg bw/day (Schmidt and Sander, 1988).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

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

Mode of Action Analysis / Human Relevance Framework

No critical adverse effects have been observed in the sub-acute oral repeated dose toxicity study in the rats.

Additional information

A study was conducted to determine the oral repeated dose toxicity of the test substance in rats according to OECD Guideline 407 and EU method B.7, in compliance with GLP. Male and female Wistar rats (6/sex/dose) were administered the following concentrations via oral gavage (suspended in water, at a constant volume of 10 mL/kg bw): 0, 40, 200 and 1000 mg/kg bw/day. Mortality, clinical signs, body weight and food consumption were recorded daily. At necropsy, blood samples were collected for haematology and clinical chemistry investigations. Also, a gross macroscopical examination was conducted, and organs were weighed. Routine histopathological examination was performed on the major organs such as heart, liver, kidneys, testes, adrenals, spleen, lungs etc. No treatment-related clinical signs of toxicity were observed. There were no treatment-related adverse effects on the body weight, food consumption, hematological and clinical biochemistry examinations could be observed. All animals at 1000 mg/kg bw/day presented a blue coloration of the visible connective tissue, particularly in the skin area, dark blue kidneys and bluish gastrointestinal contents. This was attributed to the inherent colour of the test substance. Also, in the females of the highest dose, approximately 10% higher liver weight was observed which was interpreted by the authors as a sign of a non-specific adaptation due to increased metabolic activity. Based on the results, the systemic NOAEL of the test substance for the study was considered to be 1000 mg/kg bw/day (Schmidt and Sander, 1988).

Justification for classification or non-classification

Based on the results of a repeated dose oral toxicity study in rats, no classification is warranted according to CLP (EC/1272/2008) criteria.