Disodium 5-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]azo]-4-hydroxy-6-(methylamino)naphthalene-2-sulphonate

Endpoint summary

Description of key information

The acute oral median lethal dose (LD₅₀) of Reactive Red 66 in rats of both sexes is greater than 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:

weight of evidence

Study period:

1974

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)

Principles of method if other than guideline:

The acute oral LD50 of FAT 40063/A in rats of both sexes observed over a period of 14 days.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Tif. RAI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Inhouse (bred under SPF conditions in our own breeding unit)
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160-180 g
- Fasting period before study: Overnight
- Housing: housed in Macrolon cages (Type 3) in groups of 5
- Diet: (NAFAG, Gossau SG, rat food) ad libitum.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): approx. 50 %

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

FAT 40063/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.

Doses:

4640, 6000, 7750 mg/kg bw

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: Observed at 1, 24, 48 h, 7 days and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weight, Gross pathology

Statistics:

None

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 750 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was found at any dose level

Clinical signs:

other: Within 2 hours 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. However, all animals had recovered within 8 days

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of FAT 40063/A in rats is greater than 7750 mg/kg bw

Executive summary:

FAT 40063/A was tested on 30 Tif. RAI rats (15 males and 15 females), at the dose level of 4640, 6000 and 7750 mg/kg bw. FAT 40063/A was weighed into an Erlenmeyer flask on a Mettler balance and 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. The rats were starved during one night before starting the treatment. Within 2 hours 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. All 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. Based on the study results, the acute oral median lethal dose (LD₅₀) of FAT 40063/A in rats of both sexes observed over a period of 14 days is greater than 7750 mg/kg based on test material.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 750 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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 physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

FAT 40063/A was tested on 30 Tif. RAI rats (15 males and 15 females), at the dose level of 4640, 6000 and 7750 mg/kg bw. FAT 40063/A was weighed into an Erlenmeyer flask on a Mettler balance and 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. The rats were starved during one night before starting the treatment. Within 2 hours 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. All 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. Based on the study results, the acute oral median lethal dose (LD₅₀) of FAT 40063/A in rats of both sexes observed over a period of 14 days is greater than 7750 mg/kg based on test material.

 

Acute inhalation toxicity:

Currently, no study to assess the acute inhalation toxicity potential of Reactive Red 066 is available. However, the substance is considered to have low volatility (owing to vapour pressure: 0.00607 Pa and the high melting point: >350 °C). 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 liquid formulation, the exposure via inhalation is considered to be unlikely. Further, in case the substance is entering the respiratory tract, owing to its high-water solubility, 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 STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Reactive Red 066 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 potential of Reactive Red 066 is available. However, the molecular weight of the chemical is 629.4 g/mol, indicating it being too large for dermal absorption. It has n-octanol/water partition coefficient (log P) of -2.49, 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. 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 irritation as well as sensitization studies, further supports the conclusion that low toxicity is 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. Taking above arguments into account, low toxicity potential is expected on acute dermal exposure of Reactive Red 066 and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD₅₀ of >7750 mg/kg bw in the acute oral toxicity study, the Reactive Red 066 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.