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Description of key information

Acute toxicity: oral


In the study, designated as key, a group of 10 Tif: RAIf (SPF) rats (5/sex/dose) received a single oral (gavage) dose of 2000 mg/kg bw of the test substance of ca. 93 % purity). No mortality was observed. Normal body weight gains were recorded in all the animals throughout the study. Piloerection, hunched posture and dyspnea were seen within 1 h of dosing. The animals recovered within 5-6 d. Terminal necropsy findings were normal. Under the study conditions, the oral LD50 of the test substance was > 2000 mg/kg bw (i.e. > 1860 mg a.i./L) in male/female rats.


The conclusion that Disperse Red 086 has low toxicity on oral exposure was further supported by two oral studies conducted with FAT 36034/A and FAT 36034/B, where the LD50 were estimated to be >5000 and >15000 mg/kg bw, respectively.


 


Acute toxicity: inhalation


Currently no study for assessment of acute inhalation toxicity of Disperse Red 086 is available. However, Disperse Red 086 was estimated to have low vapour pressure owing to high melting point, so the potential for the generation of inhalable forms is 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. The chemical showed low toxicity potential in the available acute oral toxicity stuies with no mortality or systemic toxicity upto 2000 mg/kg bw, hence it does not need to be classified as STOT SE. Taking above arguments into consideration, low toxicity potential is expected on acute exposure of Disperse Red 086 via inhalation route. Hence, safety for human health can be estimated via route to route extrapolation and testing by the inhalation route was considered scientifically not necessary.


 


Acute toxicity: dermal


Currently no study to assess acute dermal toxicity of Disperse Red 086 is available. However, the molecular weight of the chemical is 422.5 g/mol, indicating it being large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be limited. It was determined to have low water solubility of 3.26 mg/L, hence dermal uptake is likely to be low as the substance is considered as not sufficiently soluble in water to partition from the stratum corneum into the epidermis. Production and spray drying is performed in closed processes without isolation of reaction products. Isolated products consist either of liquid formulations or of dust free granules (non-dusty solid). In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the dermal route will be unlikely to occur. Risk management measures established for workers and professionals are considered sufficient to enable safe handling and use of the final products containing the formulated dye. No products for consumers are marketed, therefore exposure to consumers do not need to be taken into account for risk assessment. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >2000 mg/kg bw), with no mortality or systemic toxicity being seen, 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 Red 086 and testing by the dermal route was considered scientifically not necessary.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 October, 1993 to 3 November, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Test material: FAT 36034/E
Batch No.: 9300102
Expiry date: July, 1998
Purity: 93 %
Solubility: in water <0.1 g/L
Colour: red
Storage: at room temperature
Species:
rat
Strain:
other: (Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein/Switzerland
- Weight at study initiation: 174 to 237 g
- Fasting period before study: Overnight
- Housing: Macrolon cages type 4, with standardized soft wood bedding (Société Parisienne des Sciures, Pantin, France)
- Diet: Rat diet (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland), ad libitum
- Water: Ad libitum
- Acclimation period: At least for 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2 °C
- Humidity: 55±10 %
- Air changes: CA 15 air changes/h
- Photoperiod: 12 h dark/12 h light cycle

IN-LIFE DATES: From October 12, 1993 to November 3, 1993
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw (males and females)
No. of animals per sex per dose:
Five/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations: Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days; Clinical signs: Daily for 14 d: Body weight: Immediately before administration and on Days 7 and 14.
- Necropsy of survivors performed: Yes, at the end of the observation period.
Statistics:
The LD50 value with 95 % confidence limits were calculated, where possible.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 860 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities occurred in the study.
Clinical signs:
Piloerection, hunched posture and dyspnoea were seen within 1 h of test substance administration. The animals recovered within 5 to 6 d.
Body weight:
Normal body weight gains were recorded in all the animals.
Gross pathology:
No deviations from normal morphology were found in all animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance was found to be > 2000 mg/kg bw (i.e. > 1860 mg a.i./L) in male/female rats.
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance (of ca. 93 % purity) in Tif: RAIf (SPF) rats according to OECD Guideline 401and EU Method B.1 in compliance with GLP. A group of 10 animals (5/sex/dose) received a single oral (gavage) dose of 2000 mg/kg bw of the test substance. No mortality was observed. Normal bodyweight gains were recorded in all the animals throughout the study. Piloerection, hunched posture and dyspnoea were seen within 1 h of dosing. The animals recovered within 5-6 d. Terminal necropsy findings were normal. Based on the findings of the study, the oral LD50 of the test substance was >2000 mg/kg bw (i.e. >1860 mg a.i./L) in male/female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Good quality GLP study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

oral toxicity:

Based on the above stated assessment of the acute oral toxicity of Benzenesulfonamide, N-(4-amino-9,10-dihydro-3-methoxy-9,10-dioxo-

1-anthracenyl)-4-methyl- does not need to be classified as Acute Oral toxicity according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council)as implementation of UN-GHS in the EU.

- dermal toxicity:

Due to the physico-chemical properties of the test item, dermal penetration is most unlikely and the toxicologically most relevant route of exposure is the oral one. Single dose studies with oral gavage of the test substance at doses up to 2000 mg/kg body weight are available. These studies showed that the test item has a very low toxicity with an oral LD50 >2000 mg/kg body weight. Therefore it is deemed that the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- inhalation toxicity:

The test substance has very low vapor pressure and high melting point, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed. Therefore no classification for acute inhalation toxicity is deemed necessary according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.