Reaction mass of Sodium 2-(2 or 3-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate and Sodium 2-(3 or 2-{[(chloroacetyl)amino]methyl}-4-{[4-(cyclohexylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino}phenoxy)-5-methylbenzenesulfonate

Endpoint summary

Description of key information

Oral:

A study was performed to determine the acute oral toxicity of FAT 20077/A, by treating male and femaleSprague-Dawleyrats at 5000mg/kg bw and observed over a period of 14 days. A 25 % w/v solution of the compound in deionised water was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20 ml/kg (equivalent to 5000 mg/kg compound).

No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.Hence, based on these findings, the acute oral LD50 of FAT 20077/A in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of FAT 20077 is available. However, the vapour pressure for the target chemical is considered to be low owing to the high melting point >350 °C, hence its 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 humansviathe inhalation route will be unlikely to occur. Further the chemical was found to have low acute toxicity when testedviaoral route with no mortality and clinical signs when tested at 5000 mg/kg bw. Hence, considering all the above arguments, it is considered that FAT 20077 has a low toxicity potentialviainhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary. 

Dermal:

Currently no study to assess acute dermal toxicity of FAT 20077 is available. However, the molecular weight of the chemical is 710.17 g/mol, indicating it being too large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be low. The chemical showed low toxicity potential in the available acute oral toxicity study (LD₅₀>5000 mg/kg bw), with neither mortality nor clinical sings being seen. Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expectedviathe 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 FAT 20077 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:

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)

Principles of method if other than guideline:

None

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

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 weeks
- Weight at study initiation: 192 g (males), 143 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:

A 25 % w/v solution of the compound in deionised water was administered as a single dose by gavage to rats which had been fasted overnight, at a dose rate of 20 ml/kg (equivalent to 5 g/kg compound).
Ten rats (5 males and 5 females) were used for the study.

Doses:

5000 mg/kg/d

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

Statistics:

Not available

Preliminary study:

Not available

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

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.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of FAT 20077/A in rats is greater than 5000 mg/kg bw.

Executive summary:

A study was performed to determine the acute oral toxicity of FAT 20077/A, by treating male and female Sprague-Dawley rats at 5000 mg/kg bw and observed over a period of 14 days. A 25 % w/v solution of the compound in deionised water was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20 ml/kg (equivalent to 5000 mg/kg compound). No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.Hence, based on these findings, the acute oral LD50 of FAT 20077/A in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No toxicity was seen in the acute oral toxicity study with FAT 20077/A, hence the substance does not warrant classification for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.