Registration Dossier

Administrative data

Description of key information

The acute oral LD50 in rats was determined to be >10000 mg/kg bw. In total 3 studies with company data and one OECD 423 study conducted by the Japanese METI Institute are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
None
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
None
Species:
rat
Strain:
other: Tif RAI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Toxicology/Pathology, PH 2.635, CIBA-GEIGY Limited, Basle, Switzerland
- Weight at study initiation: 160 to 180 g
- Fasting period before study: overnight
- Housing: macrolon cages
- Diet: a standard diet of Nafag, Gossau SG; ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22±1 °C,
- Humidity: 55±5 %
- Photoperiod: 10 h dark/14 h light
Route of administration:
oral: gavage
Vehicle:
other: carboxymethyl-cellulose 2 %
Details on oral exposure:
DOSAGE PREPARATION:
FAT 36080/A was diluted with carboxymethyl-cellulose 2 %.

Fasting details:
Animals fasted overnight were treated by oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.
Doses:
6000, 7750 and 10000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, mortality check and autopsies
Statistics:
Not specified
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was recorded throughout the observation period.
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 days.
Body weight:
No abnormal findings reported.
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 for FAT 36080/B in rats was determined to be >10000 mg/kg bw.
Executive summary:

The acute oral LD50 of FAT 36080/B was determined in a study conducted according to a method equivalent to the OECD Guideline 401. Groups of 5 males and 5 females each, were administered the test item at the doses of 6000, 7750 and 10000 mg/kg bw. Clinical signs and mortality check were recorded during an observation period of 14 days. Autopsies were performed at the end of the observation period. No mortality was recorded throughout the observation period. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 days. No substance related gross organ changes were seen. Hence, based on the above findings, the acute oral LD50 in rats was determined to be >10000 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif: RAIf (SPF strain)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Toxicology/Pathology, PH 2.635, CIBA-GEIGY Limited, Basle, Switzerland
- Weight at study initiation: 160 to 180 g
- Fasting period before study: overnight
- Housing: macrolon cages
- Diet: a standard diet of Nafag, Gossau SG; ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Humidity: 55 ± 5 %
- Photoperiod: 10 h dark/14 h light
Route of administration:
oral: gavage
Vehicle:
other: carboxymethyl-cellulose 2 %
Details on oral exposure:
DOSAGE PREPARATION:
FAT 36080/A was suspended with carboxymethyl-cellulose 2 %. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Fasting details:
Animals fasted overnight were treated by oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.
Doses:
6000, 7750, 9000 and 10000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, mortality check and autopsies
Statistics:
Not specified
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was recorded in animals treated at 6000 and 7750 mg/kg bw. However, 1 female at the dose of 9000 mg/kg bw as well as 2 males and 1 female at the dose of 10000 mg/kg bw were found dead at the 24 hour observation after dosing.
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. Sedation and ruffled fur became more accentuated as the dose was increased. The surviving animals recovered within 8 to 9 days.
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of FAT 36080/A in rats was determined to be >10000 mg/kg bw.
Executive summary:

The acute oral LD50 of FAT 36080/A was determined in a study conducted according to the methodology that is equivalent to the OECD Guideline 401. Groups of 5 males and 5 females each, were administered the test item at the doses of 6000, 7750, 9000 and 10000 mg/kg bw. Clinical signs and mortality check were recorded during an observation period of 14 days. Autopsies were performed at the end of the observation period. No mortality was recorded in animals treated at 6000 and 7750 mg/kg bw. However, 1 female at the dose of 9000 mg/kg bw as well as 2 males and 1 female at the dose of 10000 mg/kg bw were found dead at the 24 hour observation after dosing. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. Sedation and ruffled fur became more accentuated as the dose was increased. The surviving animals recovered within 8 to 9 days. No substance related gross organ changes were seen. Hence, based on the above findings, the acute oral LD50 in rats was determined to be >10000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw
Quality of whole database:
Good quality study with detailed documentation

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

Disperse Blue 077 has been tested in several acute oral toxicity studies over the years. In a study conducted with a methodlogy similar to OECD TG 401 and considered to be a key study (1976), groups of 5 males and 5 females each, were administered Disprse Blue 077 (FAT 36080/A) at the doses of 6000, 7750, 9000 and 10000 mg/kg bw. Clinical signs and mortality check were recorded during an observation period of 14 days. Autopsies were performed at the end of the observation period. No mortality was recorded in animals treated at 6000 and 7750 mg/kg bw. However, 1 female at the dose of 9000 mg/kg bw as well as 2 males and 1 female at the dose of 10000 mg/kg bw were found dead at the 24-hour observation period. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. Sedation and ruffled fur became more accentuated as the dose was increased. The surviving animals recovered within 8 to 9 days. No substance related gross organ changes were seen. Hence based on the above findings, the acute oral LD50 in rats was determined to be >10000 mg/kg bw.

In a supporting study (1976) with Disperse Blue 077 (FAT 36080/B), groups of 5 males and 5 females each, were administered the test item at the doses of 6000, 7750 and 10000 mg/kg bw. Clinical signs and mortality check were recorded during an observation period of 14 days. Autopsies were performed at the end of the observation period. No mortality was recorded throughout the observation period. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 days. No substance related gross organ changes were seen. Hence, based on the above findings, the acute oral LD50 in rats was determined to be >10000 mg/kg bw.

In a supporting study (1987), the acute oral toxicity of Disperse Blue 077 (FAT 40278/A, active ingredient: 45 %) was evaluated according to OECD Guideline 401. A limit test was performed with the dose being 5000 mg/kg bw. A group of rats containing 5 males and 5 females was administered the test substance via gastric intubation. No mortality was observed throughout the study. Dyspnea, exophthalmos, ruffled fur and curved body position were the clinical signs observed. The animals recovered within 12 days. No effect on body weight changes were seen. No deviations from normal morphology were seen. Hence, based on these findings, the LD50 of FAT 40278/A was determined to be >5000 mg/kg bw.

Disperse Blue 077 was assessed for acute oral toxicity in a study conducted according to OECD TG 423 (acute toxic class method). The gavage of 2000 mg/kg bw dose (first and second step) to 3 females (per step) lead to no deaths during the 14 day observayion period. Decreased locomotor activity (slight), salivation, abnormal colored urine (pale purple), soft stool soiled peritoneal region, black stool and/or decreased stool volume were the clinical signs observed. No abnormalities were noted in body weight observations and at necropsies. Hence, the oral LD50 of Disperse Blue 077 was considered to be >2000 mg/kg bw.

Thus the available studies have demonstrated that Disperse Blue 077 has low toxicity when tested upto limit dose and have an acute oral LD50 of >10000 mg/kg bw.

Acute toxicity: inhalation

Currently no study to assess the acute inhalation toxicity potential of Disperse Blue 077 is available. However, as Disperse Blue 077 has a very low vapour pressure (3.41 x 10-13 Pa as estimated by Modified Grain method using MPBPVP v1.43 module available in EPISUITE v4.1), it can be considered to be of low volatility and hence the potential for the generation of inhalable forms is considered low. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on vapour pressure and/or the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further in the case, the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral toxicity studies with no mortality or systemic toxicity upto 5000 mg/kg bw, hence it does not need to be classified as STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Disperse Blue 77 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute toxicity: dermal

Currently no study to assess acute dermal toxicity of Disperse Blue 077 is available. However, physicochemical properties of Disperse Blue 077 like high molecular weight (376.32 g/mol), high partition coefficient (log Pow >6.9), and poor water solubility (<0.85 µg/L), indicate a low dermal penetration rate. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >5000 mg/kg bw), with no mortality or systemic toxicity being seen up to 2000 mg/kg bw, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected for the chemical via the dermal route. Further, experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of Disperse Blue 077 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the available data, Disperse Blue 077 does not warrant the classification for acute toxicity as per the CLP (Regulation EC No. 1272/2008) criteria.