Trisodium 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulphonatonaphthyl]azo]-2,5-dimethylphenyl]azo]benzene-1,4-disulphonate

Endpoint summary

Description of key information

The oral and dermal LD50 for Reactive Orange 35 was considered to be >2000 mg/kg bw in rats. 

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:

1975

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:

not specified

Principles of method if other than guideline:

The test substance was administered orally by gavage at single dose to a group of experimental animals. Subsequently observations of effects and deaths were made. At the end of the observation period the surviving animals were sacrificed and autopsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Name: FAT 40075/A
Purity: 74.5 %

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 234 g (males), 160 g (females)
- Fasting period before study: 18 h
- Housing: Rats were caged singly
- Diet: Commercial pelleted diet (ad libitum)
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 °C.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Route of administration:

oral: gavage

Vehicle:

other: deionised water

Details on oral exposure:

The test substance was administered as a single dose by gavage as a 25 % w/v solution in deionised water at a rate of 20 mL/kg (equivalent to 5 g/kg bw of test substance) to rats which had been fasted for 18 h.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 d.
- At the end of the observation period, surviving animals were killed by exsanguinations under other anaesthesia and an autopsy performed.
- Other examinations performed: Mortality, clinical symptoms.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 725 mg/kg bw

Based on:

act. ingr.

Mortality:

No death occurred during the study

Clinical signs:

other: No clinical signs were observed during the study period.

Gross pathology:

No changes in organs or tissues were observed at autopsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance was found to be >5000 mg/kg bw (i.e. ca. >3725 mg a.i./kg bw) in rats.

Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance (of ca. 74.5 % purity) in Sprague-Dawley rats. This test was conducted in accordance to guideline similar to OECD 401. Group of 10 fasted animals (5/sex/dose) received a single oral (gavage) dose of 5000 mg/kg bw. Parameters assessed included mortality, clinical symptoms and autopsy findings after a 14 d observation period. No mortality and no clinical symptoms were observed throughout the observation period and no significant changes in organs or tissues were seen at autopsy. Under the study conditions, the oral LD50 of the test substance was found to be >5000 mg/kg bw (i.e. ca. >3725 mg a.i./kg bw) in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

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:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity:

Acute oral toxicity of Reactive Orange 035 was evaluated in a study (1975) conducted using a methodology similar to OECD Guideline 401. In this study, a group of 10 fasted animals (5/sex/dose) received a single oral (gavage) dose of 5000 mg/kg bw. No mortality and no clinical symptoms were observed throughout the observation period and no significant changes in organs or tissues were seen at autopsy. Hence, the oral LD₅₀ of Reactive Orange 35 was found to be >5000 mg/kg bw (i.e. ca. >3725 mg a.i./kg bw) in rats.

 

Acute inhalation toxicity:

Currently no study to assess the acute inhalation toxicity potential of Reactive Orange 035 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>270 °C). Hence the substance is considered to have low volatility. 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 chemical 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 the chemical is found to have water solubility of 334 g/L, 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: >5000 mg/kg bw), with no mortality or systemic toxicity being seen, hence it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Orange 035 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

 

Acute dermal toxicity:

Currently no study to assess the repeated dose dermal toxicity of Reactive Orange 035 is available. However, the molecular weight of the chemical is 748.17 g/mol, indicating it being too large for dermal absorption. It has n-octanol/water partition coefficient (log P) of -3.46, indicating it being too hydrophilic to cross the lipid rich cell layer 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 studies (LD50 >2000 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 Orange 035 and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

The available data indicate that Reactive Orange 035 is not acutely toxic and hence it does not need to be classified for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.