Dinaphtho[1,2,3-cd:3',2',1'-lm]perylene-5,10-dione, (9,10-dihydro-9,10-dioxo-1-anthracenyl)amino derivs.

Endpoint summary

Description of key information

The acute oral LD50 of FAT 45082 in rats of both sexes observed over a period of 14 days is >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:

Study completion date: 01 April, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Code No.: FAT 45082/D
Batch No.: EN 35713.42
Stability: guaranteed by the sponsor until June, 1989
Description: solid
Test Article Received: 11 February, 1985

Species:

rat

Strain:

other: Tif:RAIf(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Weight at study initiation: 194 - 240 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing:The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Société Parisienne des sciures, Pantin).
- Diet: ad libitum.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes: approximately 15 air changes/h.
- Photoperiod: 12 hours light/day

IN LIFE Phase: Date of Administration: 26 February, 1985; Date of Completion: 12 March, 1985

Route of administration:

oral: gavage

Vehicle:

other: Distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80 (prepared by Pharmaceuticals Division, Ciba-Geigy Ltd.).

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Body weight: on days 1, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Preliminary study:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: Dyspnoea, exophthalmos, ruffled fur, and curved body positions were seen, being common symptoms in acute tests. The animals recovered within 14 days.

Gross pathology:

No deviations from normal morphology were found.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 45082/D in rats of both sexes observed over a period of 14 days is considered to be >5000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 45082/D was evaluated in a study conducted according to OECD Guideline 401. A group of rats comprising of 5 males and 5 females were administered the test substance at 5000 mg/kg bw. No mortality occured. Dyspnoea, exophthalmos, ruffled fur, and curved body positions were seen, being common symptoms in acute tests. The animals recovered within 14 days. Normal body weight gain was noted. No gross organ changes were observed. Hence, the acute oral LD50 of FAT 45082/D in rats of both sexes observed over a period of 14 days is considered to be >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 guideline 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

Oral:

The study considered as key was performed according to OECD Guideline 401. In this study, FAT 45082/D with 54.6 % purity was tested on rats by oral administration followed by a 14 observation period. No mortality occurred. Dyspnoea, exophthalmos, ruffled fur and curved body positions were observed. The animals recovered within 14 days. Based on the observations, the median lethal dose (LD50) of the test substance in both male and female rats observed for a period of 14 days was >5000 mg/kg bw.

Similar results were observed in another study performed according to OECD Guideline 401. FAT 45082/E with 28.7 % purity was tested on rats by oral administration followed by a 14 observation period. No mortality was observed. Dyspnoea, exophthalmos, ruffled fur, and curved body position were seen, being common symptoms in acute tests. Additionally, sedation was found three and five hours after the administration. The animals recovered within 8 days. Based on the observations, the median lethal dose (LD50) of the test substance in both male and female rats observed for a period of 14 days was greater than 5000 mg/kg bw.

The outcomes of the above discussed studies was further supprted by the results of the acute oral study with FAT 45082/B (purity: not known). In this study, FAT 45082/B was administered at 5000 mg/kg bw to a group of rats containing 5 males and 5 females. Based on the absence of mortality over a period of 14 days, the LD50 was again >5000 mg/kg bw.

The test material is therefore practically non-toxic to rat by oral route of administration and does not meet the criteria for classification according to GHS.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Vat Black 065 is available. However, the vapour pressure of the substance is considered to be low owing to the high melting point (>350 °C). Hence the substance is considered to have low volatility. Owing to this, the use of this substance will not result in aerosols, particles or droplets of an inhalable size. 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, no systemic toxicity or mortality were observed in the acute oral toxicity studies with Vat Black 065 (LD50: >5000 mg/kg bw). Taking into consideration above information, the acute inhalation exposure is considered to have negligible toxicity potential. Therefore testing by the inhalation route was considered scientifically not necessary and the intrinsic property/toxicity potential can be extrapolated from the acute oral toxicity study.

Dermal:

Currently no study to assess acute dermal toxicity of Vat Black 065 is available. However, the molecular weight of the substance ranges from 830.7 – 919.2 g/mol, which indicates substance is too large for dermal absorption. Further, refering to the low water solubility of the substance (<1 μg/L), the dermal uptake for the substanc is likely to be low as the substance is considered as not sufficiently soluble in water to partition from the stratum corneum into the epidermis. Production and spray drying is performed in closed processes without isolation of reaction products. Isolated products consist either of liquid formulations or of dust free granules (non-dusty solid). In addition, the use of this substance will not result in aerosols, particles or droplets owing to the low vapour pressure, so exposure to humans via the dermal route will be unlikely to occur. The substance showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>5000 mg/kg bw). Since this route does not result in mortality and/or systemic toxicity up to 5000 mg/kg bw in both male and female rats, systemic toxic effects subsequent to dermal exposure is considered to be unlikely to occur. Similarly absence of systemic toxicity or mortality in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected via dermal exposure. 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 further experiments to assess dermal toxicity are not taken into account.

Justification for classification or non-classification

The acute oral LD50 of FAT 45082 in rats of both sexes observed over a period of 14 days is >5000 mg/kg bw. The test material is therefore practically non-toxic to the rat by this route of administration.