Reaction mass of 5-[[4-[benzylmethylamino]phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium methyl sulphate and 3-[[4-[benzylmethylamino]phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium methyl sulphate

Endpoint summary

Description of key information

The acute oral LD₅₀ of Basic Red 046 Methylsulfate was determined to be 1635 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:

27 May, 1980 to 23 June, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

None

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

None

Species:

rat

Strain:

other: Tif: RAIf (SPF) strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

Healthy random bred rats of the Tif: RAIf (SPF) strain (7 to 8 weeks old) raised on the premises were used for these experiment. They were kept at a room temperature of 22±2 °C, at a relative humidity of 55±10 % and on a 10 hours light cycle day. They received ad libitum rat food - NAFAG, Gossau SG - and water. Prior to treatment the animals were adapted to our laboratories for a minimum of 4 days.

During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3 ), individually marked with picric acid.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

polyethylene glycol (PAG 400), Fluka AG, Buchs SG, Art. 81170

Details on oral exposure:

FAT 31015/F was diluted to achieve the corresponding dosage level.
Volume (ml/kg body-weight): 10, 20

Doses:

1000, 1500, 2000 and 3000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Treatment and observations:
Animals fasted overnight were treated by single oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.

Body weights:
Bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.

Autopsies:
Surviving animals were submitted to a necropsy whenever they died, survivors at the end of the observation period.

Statistics:

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

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 635 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 377 - <= 1 898

Mortality:

No mortality was observed in the rats treated at 1000 mg/kg bw. However, 1 male + 3 females and 4 males + 4 females were found dead at 1500 and 2000 mg/kg bw respectively. While, all the males and females treated at 3000 mg/kg bw were found dead.

Clinical signs:

other: The surviving animals recovered within 8 to 9 days. Sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position and tremors were clinical signs observed at the tested dose levels.

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 31016/F in rats of both sexes observed over a period of 14 days was 1635 (1377-1898) mg/kg bw

Executive summary:

The acute oral LD50 of FAT 31016/F was evaluated in a study conducted with the methodology similar to OECD Guideline 401. Groups of male and female rats (5 each) were administered with the test substance at doses of 1000, 1500, 2000 and 3000 mg/kg bw. No mortality was observed in the rats treated at 1000 mg/kg bw. However, 1 male + 3 females and 4 males + 4 females were found dead at 1500 and 2000 mg/kg bw, respectively. While, all the males and females treated at 3000 mg/kg bw were found dead. The surviving animals recovered within 8 to 9 days. Sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position and tremors were clinical signs observed at the tested dose levels. Body weights were not affected by the administration of test substance at any of the doses. No substance related gross organ changes were seen. Hence, based on the findings of the study, the acute oral LD50 of FAT 31016/F in rats of both sexes observed over a period of 14 days was 1635 (1377-1898) mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 635 mg/kg bw

Quality of whole database:

Good quality study

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:

other justification

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

The acute oral LD50 of FAT 31016/F was evaluated in a study conducted with the methodology similar to OECD Guideline 401. Groups of male and female rats (5 each) were administered with the test substance at doses of 1000, 1500, 2000 and 3000 mg/kg bw. No mortality was observed in the rats treated at 1000 mg/kg bw. However, 1 male + 3 females and 4 males + 4 females were found dead at 1500 and 2000 mg/kg bw, respectively. While, all the males and females treated at 3000 mg/kg bw were found dead. The surviving animals recovered within 8 to 9 days. Sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position and tremors were clinical signs observed at the tested dose levels. Body weights were not affected by the administration of test substance at any of the doses. No substance related gross organ changes were seen. Hence, based on the findings of the study, the acute oral LD50 of FAT 31016/F in rats of both sexes observed over a period of 14 days was 1635 (1377-1898) mg/kg bw.

Acute inhalation toxicity

Currently no study to assess the acute inhalation toxicity potential of Basic Red 046 Methylsulfate is available. However, the vapour pressure for Basic Red 046 Methylsulfate is expected to be low owing to the high boiling point (>175 °C),hence it is considered to have low volatility. The low partition coefficient of -1.86 again points to poor absorption across the respiratory tract. Basic Red 046 Methylsulfate was found to have high water solubility (734 g/L), hence the inhaled vapours may be retained within the mucus of the respiratory tract, thereby further limiting the absorption. 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, Basic Red 046 Methylsulfate was evaluated for acute oral toxicity potential yielding a LD₅₀ equal to 1635 mg/kg bw. Taking into consideration the low inhalation as well as low absorption potential if inhaled, it is expected to cause no more severe effects than already seen with acute oral toxicity study, with inhalation exposure. Hence, further experiments to assess acute inhalation toxicity were considered scientifically not necessary.

Acute dermal toxicity:

Currently no study to evaluate the acute dermal toxicity of Basic Red 046 Methylsulfate is available. The molecular weight of Basic Red 046 Methylsulfate is 432.5 g/mol, which indicates substance is too large for dermal absorption. The high water solubility (734 g/L) and low partition coefficient (log Pow = -1.86) of Basic Red 046 Methylsulfate, 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. Basic Red 046 Methylsulfate was evaluated for acute oral toxicity potential yielding a LD₅₀equal to 2289 mg/kg bw, however no substance related systemic toxicity was reported. Further, the absence of systemic toxicity or mortality in skin irritation as well as sensitization studies, further supports the conclusion that no more severe effects than already seen with acute oral exposure, are expected via dermal route. Taking into consideration the above discussion, further experiments to assess acute dermal toxicity were considered scientifically not necessary.

Justification for classification or non-classification

Based on the available information, Basic Red 046 Methosulfate needs to be classified for acute oral toxicity as category 4 (H302), as per the Regulation EC No. 1272/2008 (CLP) criteria.