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Administrative data

Description of key information

The acute oral median lethal dose (LD50) of Reactive Red 065 in rats of both sexes was >7750 mg/kg.

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:
August 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
Toxicity of FAT 40062/A in rat of both sexes observed over a period of 14 days by treating with 3 dose concentrations.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: 30 Tif. RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Huntsman/ CIBA- Geigy Limited
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 160 to 180 g
- Fasting period before study: 1 night before starting the treatment
- Housing: housed in Macrolon cages (Type 3)
- Diet: NAFAG, Gossau SG, rat food ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): approximately 50
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 %

Doses:
4640, 6000, 7750 mg/kg (No higher doses were possible)

No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1 h, 24 h, 48 h, 7 days and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: No substance related gross organ changes were seen.
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 750 mg/kg bw
Based on:
test mat.
Mortality:
One female rat died after 24 h at 7750 mg/Kg concentration.
Clinical signs:
Within 2 h after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 8 days.
Body weight:
Not provided
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of FAT 40062/A in rats of both sexes was greater than 7750 mg/kg.
Executive summary:

This study was conducted prior to GLP and test guidelines and very limited information is available for interpretation of results. Toxicity of FAT 40062/A in rat of both sexes observed over a period of 14 days by treating with 3 dose concentrations as 4640, 6000, 7750 mg/kg. The compound was tested on 30 Tif. RAI rats (15 males/ 15 females), bred under SPF conditions by in-house breeding unit. At the initiation of the treatment the rats were 6 to 7 weeks old and weighed 160 to 130 g. The rats were starved during one night before starting the treatment. The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room kept at a constant temperature of 22 +/- 1 °C and a relative humidity of approximately 50 %. They received water and food (NAFAG, Gossau SG, rat food) ad libitum. FAT 40062/A was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 30 % with polyethylene glycol (PEG 400) and administered by oral intubation. Before treatment the suspension was homogeneously dispersed with an Ultra- Turrax and during treatment it was kept stable with a magnetic stirrer. Within 2 h after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. One female rat died after 24 h at 7750 mg/Kg concentration. The surviving animals had recovered within 8 days. They were killed and autopsied after an observation period of 14 days. No substance related gross organ changes were seen. The acute oral LD50 of FAT 40062/A in rats of both sexes observed over a period of 14 days is greater than 7750 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 750 mg/kg bw
Quality of whole database:
Equivalent to OECD 401 guideline and non-GLP

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:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity:

This study was conducted prior to GLP and test guidelines and very limited information is available for interpretation of results.Toxicity of FAT 40062/A in rat of both sexes observed over a period of 14 days by treating with 3 dose concentrations as 4640, 6000, 7750 mg/kg.The compound was tested on 30 Tif. RAI rats (15 males/ 15 females). Test subsatnce was suspended at 30 % with polyethylene glycol (PEG 400) and administered by oral intubation.

 

Within 2 h after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 8 days. They were killed and autopsied after an observation period of 14 days. No substance related gross organ changes were seen. One female rat died after 24 h at 7750 mg/Kg concentration.

 

The acute oral LD50of FAT 40062/A in rats of both sexes observed over a period of 14 days is greater than 7750 mg/kg.

Acute Inhalation Toxicity:

Currently no study to assess the acute inhalation toxicity potential of Reactive Red 065 is available. The vapour pressure of the substance is low (7.43 × 10-7 Pa) with high melting point (>350 °C), hence the substance is considered to have low volatility. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulations only. 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 unlikely occur. Further, Reactive Red 65 was found to be miscible in water (water solubility 12.9 g/L) and have low log partition coefficient <-3.56), hence in the case of dust of 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 study (LD50>7750 mg/kg bw), with no mortality or systemic toxicity, hence it does not need to be classified as STOT SE. Taking above arguments into account, low toxicity potential is expected on acute exposure of Reactive Red 065 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute Dermal Toxicity:

Currently no study to assess the acute dermal toxicity of Reactive Red 065 is available. However, the molecular weight of the chemical is 615.3 g/mol, indicating it being too large for dermal absorption. It has water solubility of 12.9 g/L and n-octanol/water partition coefficient (log P) of < -3.56, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance will be low. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulations only. 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. The chemical showed low toxicity potential in the available acute oral toxicity study (LD50>7750 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Similarly, absence of local toxicity in skin and eye irritation studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Taking above arguments into account, low toxicity potential is expected on acute exposure of Reactive Red 065 via dermal route and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD50of >7750 mg/kg bw in the acute oral toxicity study, Reactive Red 65 does not considered to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.