Reaction mass of 5-[{4-[Benzyl(methyl)amino]phenyl}diazenyl]-1,4-dimethyl-4H-1,2,4-triazol-1-ium bromide and 3-[{4-[Benzyl(methyl)amino]phenyl}diazenyl]-1,4-dimethyl-4H-1,2,4-triazol-1-ium bromide

Endpoint summary

Description of key information

The acute oral LD₅₀ of Basic Red 046 Bromide was determined to be 1129 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:

Experiment start date - 27 August 1980; Experiment end date - 22 September 1980; Study completion date - 02 October 1980.

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:

no

GLP compliance:

no

Test type:

standard acute method

Specific details on test material used for the study:

Name: FAT 31016/C
Purity: 85 %

Species:

rat

Strain:

other: Tif: RAif (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Inhouse breeding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 - 8 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod: 10 hours light.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

400

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

300, 1000, 3000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology.

Statistics:

LD50 including 95 % confidence limits are calculated by the logit model.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 129 mg/kg bw

Based on:

test mat.

95% CL:

> 535 - <= 2 055

Mortality:

At 300 mg/kg: 0/5 males and females each died.
At 1000 mg/kg: 1/5 males were found dead, 5/5 females were found dead.
At 3000 mg/kg: 4/5 males and females each were found dead.

Clinical signs:

other: Sedation, dyspnoea, exopthalamos, ruffled fur, hunched posture was observed in all animals.

Gross pathology:

No substance related gross organ change was noted.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was calculated to be 1129 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted according to guideline equivalent or similar to OECD TG 401 to evaluate toxicity of FAT 31016/C. The test substance was suspended with polyethylene glycol (PEG 400). Doses of 300, 1000 and 3000 mg/kg bw were administered to rats divided in four groups each containing 5 males and 5 females. The treated animals were observed for 14 days for clinical signs and mortality.

Mortality: At 300 mg/kg: 0/5 males and females each died.

At 1000 mg/kg: 1/5 males were found dead, 5/5 females were found dead.

At 3000 mg/kg: 4/5 males and females each were found dead.

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. No substance related gross organ changes were seen at post mortem examinations. Based on the findings of the study, the acute oral LD50 of FAT 31016/C in rats of both sexes observed over a period of 14 days was found to be 1129 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 129 mg/kg bw

Quality of whole database:

Good quality study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

An acute oral toxicity study was conducted according to guideline equivalent or similar to OECD TG 401 to evaluate toxicity of FAT 31016/C. The test substance was suspended with polyethylene glycol (PEG 400). Doses of 300, 1000 and 3000 mg/kg bw were administered to rats divided in four groups each containing 5 males and 5 females. The treated animals were observed for 14 days for clinical signs and mortality.

Mortality: At 300 mg/kg: 0/5 males and females each died.

At 1000 mg/kg: 1/5 males were found dead, 5/5 females were found dead.

At 3000 mg/kg: 4/5 males and females each were found dead.

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. No substance related gross organ changes were seen at post mortem examinations. Based on the findings of the study, the acute oral LD50 of FAT 31016/C in rats of both sexes observed over a period of 14 days was found to be 1129 mg/kg bw.

 

Acute inhalation toxicity

Currently no study is available to assess the acute inhalation toxicity potential of Basic Red 046 Bromide. The calculated value for vapour pressure is expected to be low owing to the high boiling point (>170 °C), hence it 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 7.9 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. Further, results from acute oral toxicity studies are available for consideration, where the lowest LD50 was 1129 mg/kg bw, with no systemic toxicity being seen, hence it does not need to be classified STOT SE. Taking the above arguments into consideration, no more severe effects compared to the oral route are expected upon acute exposure of Basic Red 046 Bromide via inhalation route and safety for human health can be estimated using the principle of route to route extrapolation. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Basic Red 046 Bromide 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 Basic Red 046 Bromide is available. However, the molecular weight of Basic Red 046 Bromide is 401.3 g/mol, indicating it being too large for dermal absorption. It has water solubility of 7.9 g/L and n-octanol/water partition coefficient (log P) of –1.43, 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. Further, results from acute oral toxicity studies are available for consideration, where the lowest LD50 was 1149 mg/kg bw, with no systemic toxicity being seen, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation and sensitisation studies further supports the conclusion that no adverse effects are 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 consideration, low toxicity is expected on acute dermal exposure of Basic Red 046 Bromide and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the available information, Basic Red 046 Bromide does not warrant classification for acute toxicity as per the Regulation EC No. 1272/2008 (CLP) criteria.