Pentasodium bis[5-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-4-hydroxy-3-[(2-hydroxy-5-nitrophenyl)azo]naphthalene-2,7-disulphonato(4-)]chromate(5-)

Endpoint summary

Description of key information

The oral LD50 was determined to be greater than 5000 mg/kg bw. 

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:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animal: Rat, KFM-Han, Wistar (outbred, SPF-quality);
Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerlan;
Number of animals: 5 males and 5 females; Total number: 10 males and 10 females;
Age of start of treatment: 9-11 weeks;
Body weight at start of the treatment: males:203-240g and female: 181-212 g.
Identification: by unique cage number and corresponding color-coded spots;
Randomization: randomly selected at time of delivery in groups of five.
Acclimation: at least one week under laboratory conditions, after veterinary examination.
Environmental conditions: Standard laboratory conditions: air-conditioned with 10-15 air changes per hour, and hourly monitored environment with temperature 22±3 °C, relative humidity 40-70 %, 12 hours artificial fluorescent light/12 hours dark, music/light period.
Accommodation: Group of five in Makrolon type-3 cages with standard softwood bedding. The cages were cleaned twice weekly during the test period.
Diet: Pelleted standard Kliba 343, batch 36/85 rat maintenance diet available ad libitum.
Water: community tap water from Itingen, available ad libitum.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The animals received the test article on a mg/kg body weight base by oral gavage after being fasted for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately one hour after dosing.

Doses:

20 ml at 3000 mg/kg bw (group 1) and 5000 mg/kg (group 2) bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

FAT 40210/A was administered to rats of both sexes (5 male and 5 female for each group) by oral gavage at doses of 3000 and 5000 mg/kg bw and death rate, symptoms and necropsy were observed and the acute oral toxicity of FAT 40210 was estimated.

Statistics:

None

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

0 % at 3000 mg/kg bw and 10 % at 5000 mg/kg bw

Clinical signs:

other: 3000 mg/kg bw: sedation, dyspnoea, curved body position, ruffled fur, extremities blue to black discoloured. 5000 mg/kg bw: sedation, dyspnoea, ataxia, curved body position, ruffled fur, extremities blue to black discoloured. The rats had recovered from t

Gross pathology:

3000 mg/kg bw - killed: Stomach: partly blue discoloured (10); Kidneys/skin: dark-blue discoloured (5), blue discoloured (5);
5000 mg/kg bw - dead: Lung: blue discoloured, slight (1); Stomach/Intestines: blue to black discoloured, severe (1); adipose tissure: blue discoloured, slight (1);
5000 mg/kg bw- males: Stomach: blue discoloured (9); Intestines: blue discoloured slight (9); Urinary bladder, kidneys, skin: blue discoloured (9). Testis: blue discoloured (4); Uterus: blue discoloured (5).

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity of FAT 40210/A in rats of both sexed, observed over a period of 15 days, was estimated to be greater than 5000 mg/kg bw.

Executive summary:

A key study was performed to determine the oral acute toxicity in rats according to OECD Guideline 401 (Acute Oral Toxicity).

The test article FAT 40210/A was administered to rats of both sexes by oral gavage, at doses from 3000 to 5000 mg/kg bw. The following death rate was observed: 0 % at 3000 mg/kg bw and 10 % at 5000 mg/kg bw. The LOGIT-Model could not be applied to these data. And the acute oral toxicity of FAT 40210/A in rats of both sexed, observed over a period of 15 days, was estimated to be greater than 5000 mg/kg bw, which shall not be classified according to CLP Regulation (Regulation [EC] No. 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Good quality studies

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:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

- Oral toxicity:

FAT 40210 was tested in three acute oral toxicity studies. In the key study, performed according to OECD Guideline 401, the LD50 was determined to be >5000 mg/kg bw. In this study, no mortality was observed at 3000 mg/kg bw, while 10 % mortality was seen with 5000 mg/kg bw.

The outcome of the key study was supported by the supporting studies, as no mortality was seen in these studies even at the highest dose of 5000 mg/kg bw.

- Inhalation toxicity:

Currently no study to assess the acute inhalation toxicity potential of the target chemical, Reactive Black 8, is available. However, the vapour pressure for the target chemical is considered to be low owing to the high melting point, hence it is considered to have low volatility. The low partition coefficient of <-6.29 at 20 °C again point to poor absorption across the respiratory tract. The substance was found to have high water solubility (443 g/L), hence the inhaled dust may be retained within the mucus of the respiratory tract, thereby limiting absorption in the lung. The test item synthesis and spray drying are performed in a closed process; the final product consists of non-dusty granules. In addition, 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. Further, the substance was found to have low acute toxicity when tested via oral route. Hence, considering all the above arguments, it is considered that the substance has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is being waived. 

- Dermal toxicity:

Currently no study to assess acute dermal toxicity of the target chemical, Reactive Black 8, is available. However, the molecular weight of the substance is 1384.8 g/mol, which indicates the substance being too large for dermal absorption. Further, high water solubility (443 g/L) and low partition coefficient (<-6.29), indicate the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance is expected to be low. The substance showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>5000 mg/kg bw). Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected 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 substance only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of the target chemical and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

- Oral toxicity:

Based on the above stated assessment of the acute oral toxicity of Reactive Black 8 the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- Dermal toxicity:

As no local or systemic effects were noted in local irritation studies in rabbits the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- Inhalation toxicity:

Due to the very low vapour pressure of the substance and the fact that the substance is formulated as a dust-free powder or granulate the inhalation route of exposure is considered to be unlikely. 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 CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.