C.I. Acid Yellow 246

Endpoint summary

Description of key information

The acute oral and dermal median lethal dose (LD50) of FAT 20306/B is determined to be greater than 5000 and 2000 mg/kg bw, respectively.

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 July 1984 to 29 August 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:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Code No: FAT 20306/B
Batch No: HT 2025/50
Stability: 30 years
Description; solid
Contents of active ingredient: approx. 96 %

Species:

rat

Strain:

other: Rat, Tif:RAIf(SPF), F3-crosses of RII 1/Tif x RII 2/Tif

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: 178 - 202 g
- Fasting period before study: overnight
- Housing: They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bed-ding.
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland) was provided ad libitum.
- Water: water was provided 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

Route of administration:

oral: gavage

Vehicle:

other: 01. arachidis Ph. H. VI Siegfried AG

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg body weight
- Rationale for the selection of the starting dose: 5000 mg/kg bw

Doses:

one single dose of 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 7 and 14 day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

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)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality found

Mortality:

No mortality

Clinical signs:

other: Dyspnoea, exophthalmos, ruffled fur, and curved body position and a slight diarrhoea were observed. However, the animals recovered within 13 days.

Gross pathology:

No gross organ changes were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Acute oral median lethal dose (LD50) of FAT 20306/B is determined to be greater than 5000 mg/kg bw.

Executive summary:

In an acute oral toxicity study carried out with FAT 20306/B in rats according to OECD guideline 401, the test article was administrated to rats (5/sex) by oral gavage at one single dose of 5000 mg/kg. No mortality was observed. Dyspnoea, exophthalmus, ruffled fur, and curved body position and a slight diarrhoea were observed . However, the animals recovered within 13 days. No gross organ changes were observed. Based on the study results, acute oral median lethal dose (LD50) of FAT 20306/B is determined to be 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:

Guideline 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

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 July 1984 to 29 August 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Code No: FAT 20306/B
Batch No.: HT 2025/50
Stability: 30 years
Description; solid
Contents of active ingredient approx. 96 %

Species:

rat

Strain:

other: Tif:RAIf(SPF), F3-crosses of RII 1/Tif x RII 2/Tif

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: 192 - 215 g
- Fasting period before study: overnight
- Housing: They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding.
- Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland) was provided ad libitum.
- Water: water was provided 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

Type of coverage:

semiocclusive

Vehicle:

other: 0l. arachidis Ph. H. VI Siegfried AG

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10 %
- Type of wrap if used: adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg hody weight

Duration of exposure:

24 h

Doses:

single dose of 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on working days, daily, a.m. and p.m. a.m. on weekends for mortaility; on days 1, 7, 14 and at death for body weight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortailty

Clinical signs:

other: Dyspnoea, exophthalmos, ruffled fur and abnormal body positions.

Gross pathology:

No tireatment-related deviations from normal morphology detected.

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

An acute dermal median lethal dose (LD50) of FAT 20306/B to rat is greater than 2000 mg/kg bw.

Executive summary:

In an acute dermal study carried out with FAT 20306/B in rats according to OECD guideline 402, the test substance was applied to the skin of rats (5/sex) for 24 hrs at a dose of 2000 mg/kg. No mortality was observed at test concentration. No deviation from normal morphology at necropsy. No treatment-related deviations from normal morphology was detected in any animal. Dyspnoea, exophthalmus, ruffled fur and abnormal body positions were observed, but all rats had recovered within 12 days. Based on the study results, the LD50 of test substance 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:

Guideline study

Additional information

Acute Toxicity: Oral

In an acute oral toxicity study carried out with FAT 20306/B in rats according to OECD guideline 401, the test article was administrated to rats (5/sex) by oral gavage at one single dose of 5000 mg/kg. No mortality was observed. Dyspnoea, exophthalmus, ruffled fur, and curved body position and a slight diarrhoea were observed . However, the animals recovered within 13 days. No gross organ changes were observed. Based on the study results, acute oral median lethal dose (LD50) of FAT 20306/B is determined to be greater than 5000 mg/kg bw.

 

Acute Toxicity: Inhalation

Currently no study to assess the acute inhalation toxicity potential of Acid Yellow 246 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>287 °C). 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. Further, the chemical is found to have water solubility of >100 g/L and have low log partition coefficient (-0.77), hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral and dermal 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 toxicity in skin irritation study and systemic toxicity in skin sensitization study, further supports the conclusion that low toxicity is expected for the chemical via the inhalation route. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Acid Yellow 246 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

 

Acute Toxicity: Dermal

In an acute dermal study carried out with FAT 20306/B in rats according to OECD guideline 402, the test substance was applied to the skin of rats (5/sex) for 24 hrs at a dose of 2000 mg/kg. No mortality was observed at test concentration. No deviation from normal morphology at necropsy. No treatment-related deviations from normal morphology was detected in any animal. Dyspnoea, exophthalmos, ruffled fur and abnormal body positions were observed, but all rats had recovered within 12 days. Based on the study results, the LD50 of test substance was estimated to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the observed LD₅₀ of >2000 mg/kg bw in the acute oral and dermal 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.