5-[(4-chloro-2-nitrophenyl)azo]-1-ethyl-1,2-dihydro-6-hydroxy-4-methyl-2-oxonicotinonitrile

Endpoint summary

Description of key information

The acute oral LD50 of FAT 36091/D in rats of both sexes observed over a period of 14 days is approximately 8000 mg/kg.

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:

Experiment start date: 06 December 1979; Experiment end date: 04 February 1980; Study completion date: 07 March 1980.

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)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Name: FAT 36091/D
Purity: 50.2 %

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 experiments. 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. 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:

CMC (carboxymethyl cellulose)

Remarks:

2% (w/v) in dist. water.

Details on oral exposure:

VEHICLE
Volume (ml/kg body-weight): 20

The test item was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

5000, 7000, 8000 and 10000 mg/kg.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight.

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.

Statistics:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 8 000 mg/kg bw

Based on:

test mat.

Mortality:

At 5000 mg/kg: No deaths observed.
At 7000 mg/kg: 1 male died
At 8000 mg/kg: 2 male and 3 female died
At 10000 mg/kg: 3 male and 2 female died

Clinical signs:

other: - Sedation, dyspnoea, ruffled fur, diarrhoea, body position curved were observed at 5000 mg/kg. The surviving animals recovered within 7 days. - Sedation, dyspnoea, ruffled fur, diarrhoea, body position curved were observed at 7000 mg/kg. The surviving an

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

No data

Body weight changes:

	Dose (mg/kg)
		5000	7000	8000
Day 1 Male	Mean body weight/SD (g)	208/18.4	185/14.2	188/9.0	188/11.4
Day 1 female	Mean body weight/SD (g)	180/8.3	180/5.9	174/7.3	173/4.6
Day 7 Male	Mean body weight/SD (g)	243/23.4	239/16.7	220/10.0	247/11.3
Day 7 female	Mean body weight/SD (g)	205/13.6	198/8.6	193/10.6	195/.0.
Day 14 Male	Mean body weight/SD (g)	290/25.5	280/21.9	261/12.9	293/20.5
Day 14 female	Mean body weight/SD (g)	237/27.8	212/3.8	223/15.6	218/8.1

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 36091/D in rats of both sexes observed over a period of 14 days is approximately 8000 mg/kg.

Executive summary:

A study was conducted according to method similar or equivalent to OECD TG 401 to determine the acute oral toxicity of the test on rats via oral route. 5 males and 5 females were given following doses; 5000, 7000, 8000, 10000 mg/kg bw. Physical condition and rate of deaths were monitored throughout the whole observation period. Doses of 5000 to 10000 mg/kg bw was given by oral gavage. Before administration, the test item was prepared in CMC (Carboxymethyl cellulose).

Mortality;

At 5000 mg/kg: No deaths observed.

At 7000 mg/kg: 1 male died

At 8000 mg/kg: 2 male and 3 female died

At 10000 mg/kg: 3 male and 2 female died

Symptoms were observed in all dose levels: Sedation, dyspnoea, ruffled fur, diarrhoea, body position curved. The surviving animals recovered within 7 to 8 days. The acute oral LD50 of FAT 36091/D in rats of both sexes observed over a period of 14 days is approximately 8000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 000 mg/kg bw

Quality of whole database:

The experiment was performed according to a guideline equivalent or similar to the OECD Guideline 401 (Acute Oral toxicty).

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

Additional information

Acute toxicity: oral

A n in vivo study was performed to determine the acute oral toxicity of FAT 36091 (batch D) on rats equivalent or similar to the OECD Guideline 401 (Acute Oral toxicity). 5 males and 5 female Tif. RAI rats where exposed at each dose level (5000/7000/8000 and 10000 mg/kg bw) and observed for 14 consecutive days. Symptoms were observed in all dose levels: Sedation, dyspnoea, ruffled fur, diarrhoea, body position curved. The surviving animals recovered within 7 to 8 days. The LD50 was determined to ca. 8000 mg/kg bw in rats of both sexes. A second (supporting) study was carried out to determine of the acute oral toxicity of FAT 36091, (batch A), using Tif. RAI rats. Before administration by gavage, FAT 36091 was suspended in carboxymethyl cellulose (CMC).The test material was administered at different doses to 5 males and 5 females. Symptoms were observed in all dose levels. All surviving animals recovered within 10 days. The acute oral LD50 of FAT36091/A in rats of both sexes observed over a period of 14 days is found to be 6058 mg/kg (5248-6992).

Acute toxicity: inhalation
Currently no study is available to assess the acute inhalation toxicity potential of Disperse yellow 211. The calculated value for vapour pressure was found to be 1.1E-8 Pa at 25 °C. Hence the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in closed processes; 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. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50: >2000 mg/kg bw), with no systemic toxicity being seen, hence it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Disperse yellow 211 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute toxicity: dermal

Currently no study to assess acute dermal toxicity of Disperse Yellow 211 is available. However, the molecular weight of the chemical is 361.7 g/mol, indicating limited dermal absorption. The substance has low solubility in water (3.9 mg/L), hence dermal uptake 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. Further, no adverse effects were observed in acute oral studies (LD50 >2000 mg/kg) suggesting that the substance has low toxicity, hence it does not need to be classified as STOT SE. Hence no significant toxicity is expected via dermal route and safety for human health can be estimated via route to route extrapolation. Similarly, absence of systemic toxicity or mortality in skin irritation and sensitization studies, supports the conclusion that no adverse effects are expected via dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the test item 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 36091/D in rats of both sexes observed over a period of 14 days is approximately 8000 mg/kg. The test item does not meet the criteria for classification according to the Globally Harmonized Classification System.