N-[2-[(2-cyano-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide

Endpoint summary

Description of key information

Acute Oral Toxicity Study:

FAT 36156/D was assessed for acute toxicity potential via ora route according to OECD Guideline 420 and EU Method B.1. Following a sighting test at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths and no signs of systemic toxicity. However, green stained feces were noted in the initial treated animal. Animals showed expected gains in body weight, except for one animal which showed expected gain in body weight during the first week but body weight loss during the second week. No abnormalities were noted at necropsy.In conclusion, the acute oral median lethal dose (LD₅₀) of FAT 36156/D in the female Wistar rat was estimated to be greater than 2000 mg/kg bw. In a supporting study, FAT 36156/A was assessed for acute toxicity potential via oral route in albino rats. The study was carried out according to the OECD Guideline 401. Five rats per sex were used at each dose of 2000 and 5000 mg/kg bw. No mortality was seen at 2000 mg/kg bw, however 3 males and 2 females at 5000 mg/kg bw were found dead on Day 1. Hence, the acute oral median lethal dose (LD₅₀) in rats was greater than 2000 mg/kg bw.

 

 

Acute Inhalation Toxicity Study:

Currently no study to assess the acute inhalation toxicity potential of Disperse Blue 165:1 is available. However, the vapour pressure for the substance can be considered low (2.2 x 10^-11Pa). Hence, the substance 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 substance is imported into the EU in a formulated form as liquid formulation, the exposure via inhalation is considered to be unlikely. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Disperse Blue 165-1 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

 

Acute Dermal Toxicity Study:

Currently no study to assess the acute dermal toxicity of Disperse Blue 165:1 is available. However, it possesses molecular weight of 425.4 g/mol, hence considered to have limited dermal absorption. Also, it was found to have very low solubility in water (0.20 mg/L), hence dermal uptake is likely to be low as the substance is considered as not sufficiently soluble in water to partition from theStratum corneuminto the epidermis, again indicating limited dermal absorption. Synthesis and spray drying of this chemical is performed in a closed process; without isolation of reaction products. Isolated products consist of either liquid formulations or dust free granules (non-dusty solid). In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the dermal route will be unlikely to occur. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Similarly, absence of local or systemic toxicity in skin irritation and sensitisation studies further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Taking above arguments into account, low toxicity potential is expected on acute exposure of Disperse Blue 165 -1 via dermal route and hence acute toxicity 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:

25 August 2015 to 3 November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Test material identified as: FAT36156/D TE

SOURCE OF TEST MATERIAL
- Batch number of test material:
20140804
- Expiration date of the lot/batch:
21 August 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
room temperature in the dark

Species:

rat

Strain:

Wistar

Remarks:

RCCHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
8 to 12 weeks
- Weight at study initiation:
159 to 186 g
- Fasting period before study:
Overnight
- Housing:
in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
19 to 25
- Humidity (%):
30 to 70
- Air changes (per hr):
15
- Photoperiod (hrs dark / hrs light):
12 hours continuous light and 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

arachis oil

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths found during the study period.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period. However, green stained feces was noted in the initial treated animal on Days 1 to 6.

Gross pathology:

No abnormalities were noted at necropsy.

Individual Clinical Observations and Mortality Data

 

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	0	0	0F	0F	0F	0F	0F	0F	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 =     No signs of systemic toxicity

F =      Green stained feces

 

 

Individual Body Weights and Body Weight Changes 

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	160	180	188	20	8
	2-0 Female	159	173	200	14	27
	2-1 Female	171	188	199	17	11
	2-2 Female	186	203	200	17	-3
	2-3 Female	164	176	180	12	4

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the FAT 36156/D in the female Wistar rat was estimated to be greater than 2000 mg/kg bw.

Executive summary:

FAT 36156/D was assessed for acute toxicity potential via ora route according to OECD Guideline 420 and EU Method B.1. Following a sighting test at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths and no signs of systemic toxicity. However, green stained feces were noted in the initial treated animal. Animals showed expected gains in body weight, except for one animal which showed expected gain in body weight during the first week but body weight loss during the second week. No abnormalities were noted at necropsy. In conclusion, the acute oral median lethal dose (LD₅₀) of FAT 36156/D in the female Wistar rat was estimated to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

High quality GLP 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

Justification for classification or non-classification

Based on the observed LD₅₀of >2000 mg/kg bw in the acute oral toxicity study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.