Disodium [4-hydroxy-3-[(2-hydroxy-4-nitrophenyl)azo]naphthalene-1-sulphonato(3-)][1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphtholato(2-)]chromate(2-)

Endpoint summary

Description of key information

Oral:

In total four acute oral toxicity studies performed according to OECD testing guidelines are available. The key study was performed to assess the acute oral toxicity of FAT 20011/E in the Wistar strain rats., according to OECD Guideline 420 and EU Method B.1.

Following a sighting test at a dose level of 3077 mg/kg (equivalent to 2000 mg active ingredient/kg bw) in one female rat, an additional four fasted female animals were given a single oral dose of test item, as a solution in distilled water, at a dose level of 3077 mg/kg bw ( equivalent to 2000 mg active ingredient/kg bw). No deaths were observed during the course of study. There were no signs of systemic toxicity. Blue or blue/black colored staining of the feces was noted in all animals. Blue colored staining of the urine was also noted in the four additional treated animals. All animals showed expected gains in body weight. No abnormalities were noted at necropsy of the initial treated animal. Patchy pallor of the liver and dark kidneys were noted at necropsy of the four additional treated animals.Based on these findings, the acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 3077 mg/kg body weight (equivalent to 2000 mg/kg active ingredient/kg body weight) (Globally Harmonized Classification System - Unclassified). In another experiment considered as supporting study and performed in 1994 to determine the acute oral toxicity of FAT 2001/D (purity 52.5 %), a group of rats (5/sex) were gavaged at 2000 mg/kg bw and observed over a period of 14 days. Within 2 hours after treatment, the rats showed piloerection, hunched posture and dyspnoea, but recovered within 3 days. No substance related gross organ changes were noted. Based on these findings, the acute oral LD50 of FAT 20011/D in rats of both sexes observed over a period of 14 days is greater than 2000 mg/kg bw (based on test material). In a supporting study performed in 1974 to determine the acute toxicity of FAT 20011/A (purity 40 %) according to a methodology similar to OECD Guideline 401 (Acute Oral Toxicity), a group of rats containing 5 males and 5 females were administered the test item at 5000 mg/kg bw. No mortality was observed. Signs of reaction to treatment, observed shortly after treatment, included lethargy, piloerection, diuresis and diarrhoea. The urine and faeces of all rats were stained blue. Recovery of all animals, as judged by external appearance and behaviour, was apparently complete two days after treatment. This observation was substantiated by normal bodyweight increases compared with controls. Autopsy findings were normal. In conclusion, the acute oral LD50 of FAT 20011/A in rats of both sexes, observed over a period of 14 days is greater than 5000 mg/kg. In the study performed in 1982 to determine the acute oral toxicity of FAT 20011/C (purity 52.5 %), groups of rats (5/sex/dose) received the test item at 1000, 2500 and 5000 mg/kg bw. Within 2 hours after treatment, rats of all dosage groups showed piloerection, hunched posture and dyspnea, but recovered within 3 days in the mid (except one female) and low dose groups. In the high dose group death rates of 60 % in males and 100 % in females occurred. In addition one female of the mid dose group also died within the first day post treatment. No gross pathological changes have been noted neither in the animals died subsequently to test substance administration nor in the survivors. Based on the findings of the study, the acute oral LD50 of FAT 20011/C in male rats is >2500, in female rats is 2800 and rats of both sexes observed over a period of 14 days is 3644 mg/kg bw (based on test material). Taking all available data from the above studies into account, the LD50 for acute oral toxicity is set to 2000 mg/kg bw.

 

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Acid Blue 317 is available. However, the vapour pressure for the target chemical is low owing to the high melting point >330 °C, hence it can be 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. Further, the chemical was found to have low acute toxicity when tested via oral route with no mortality when tested upto 2000 mg/kg bw. Hence, considering all the above arguments, it is considered that Acid Blue 317 has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary.

 

Dermal:

Currently no study to assess acute dermal toxicity of Acid Blue 317 is available. However, the molecular weight of the chemical is 791.55 g/mol, indicating low potential for dermal absorption. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >2000 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 chemical only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of Acid Blue 317 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:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Identification: FAT 20011/E TE
Batch: 130923 (China)
Purity: 65 %
Physical state / Appearance: dark blue solid
Sponsor (bulk) description: black powder which makes a blue solution.
Expiry date: 30 Sept 2018
Storage Conditions: room temperature in the dark

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK.
- Weight at study initiation: 154 - 170 g
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Photoperiod: 12 hours light/day

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): Volume (ml/kg body weight) applied: 10

Doses:

3077 mg/kg bw (2000 mg a.i./kg bw)

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days or until all symptoms have disappeared, whichever lasts longer
- Frequency of observations: Clinical observations were made 30 minutes, I, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: yes, At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 3 077 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period. Blue/black colored staining of the feces was noted in the initial treated animal 1 to 5 days after dosing. Blue colored staining of the urine and/or feces was noted in the four additi

Gross pathology:

No abnormalities were noted at necropsy of the initial treated animal. Patchy pallor of the liver and dark kidneys were noted at necropsy of the four additional treated animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 3077 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).

Executive summary:

The study was performed to assess the acute oral toxicity of FAT 20011/E in the Wistar strain rats, according to OECD Guideline 420 and Method B.1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008. Following a sighting test at a dose level of 3077 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw) in one female rat, an additional four fasted female animals were given a single oral dose of test item, as a solution in distilled water, at a dose level of 3077 mg/kg bw ( equivalent to 2000 mg active ingredient/kg bw). Mortality, clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy after observation period of 14 days. No deaths were observed during the course of study. No signs of systemic toxicity were noted during the observation period. Blue/black colored staining of the feces was noted in the initially treated animal 1 to 5 days after dosing. Blue colored staining of the urine and/or feces was noted in the four additional treated animals 2 hours to 7 days after dosing. All animals showed expected gains in body weight. No abnormalities were noted at necropsy of the initially treated animal. Patchy pallor of the liver and dark kidneys were noted at necropsy of the four additional treated animals.Based on these findings, the acute oral median lethal dose (LD50) of the test item in the female Wistar strain rats was estimated to be greater than 3077 mg/kg bw (equivalent to 2000 mg/kg active ingredient/kg bw) (Globally Harmonized Classification System - Unclassified).

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:

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

Justification for classification or non-classification

The oral LD50 for Acid Blue 317 is considered to be >2000 mg/kg bw based on the data from available studies, hence it does not warrant classification for acute toxicity in accordance with the criteria of Regulation (EC) No. 1272/2008.