6,18-dihydrodinaphtho[2,3-i:2',3'-i']benzo[1,2-a:4,5-a']dicarbazole-5,7,12,17,19,24-hexone

Endpoint summary

Description of key information

Oral:

The study considered as key was performed according to OECD Guideline 401. In this study, FAT 46014/F with 35.7% purity was tested on rats by oral administration followed by a 14 day observation period. No mortality was seen at the administered dose of 5000 mg/kg bw. Dyspnoea, exophthalmos, ruffled fur and curved body positions were observed. In addition, a transient diarrhea and tremor was observed. The animals receovered within 10 days. At necropsy, no substance related gross organ changes were seen. 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.

 

In several other supporting studies, LD50 values of > 10000, >15000 and > 8000 mg/kg were recorded.

 

The above values show that FAT 46014 is non-toxic via oral route of administration.

 

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Vat Orange 011 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 Orange 011 upto 5000 mg/kg bw. Taking into consideration the 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 Orange 011 is available. However, the molecular weight of the substance is 646.6 g/mol, which indicates substance is too large for dermal absorption. Further, referring to the low water solubility of the substance (<1 μg/L), the dermal uptake for the substance 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.

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: 28 March, 1984

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 46014/F
Batch No. : EN 94071.32
Stability: guaranteed by the sponsor until November 1988
Description: solid
Contents of active ingredient: 35.7 %
Test Article Received: December 6, 1983

Species:

rat

Strain:

other: Tif. RAI (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 179-215 g
- 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 (per hr): approximately 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hours light/day

IN LIFE PHASE: From: 01 February, 1984; To: 15 February, 1984

Route of administration:

oral: gavage

Vehicle:

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

Details on oral exposure:

- Amount of vehicle (if gavage): 20 ml/kg
The animals were allocated to the different dose groups by random selection.
Prior to dosing, the animals were fasted overnight.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males/5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, symptoms, body weight.

Statistics:

From the body weights, the group means and their standard deviations were calculated.
Where feasible, the LD50 including the 95% confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944).

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:

Dyspnoea, exophthalmos, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, a transient diarrhea and tremor was observed. The surviving animals recovered within 10 days.

Body weight:

No effect on body weight gains was seen.

Gross pathology:

No gross lesions were found at necropsy.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The acute oral LD50 of FAT 46014/F in rats of both sexes observed over a period of 14 days is 5000 mg/kg.

Executive summary:

The acute oral toxicity of FAT 46014/F was assessed in a study conducted according to OECD Guideline 401. In this study, a group of 5 male and 5 female rats were administered a dose of 5000 mg/kg bw. No mortality was seen. Dyspnoea, exophthalmos, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, a transient diarrhea and tremor was observed. The surviving animals recovered within 10 days. No adverse effect on body weight gain was seen. No gross lesions were found at necropsy. Thus, based on the findings of the study, the LD50 of FAT 46014/F was determined 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

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 substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The LD50 value for FAT 46014/F upon oral administration was found to be greater than 5000 mg/kg bw. Hence, it does not warrant classification for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.