Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The acute oral LD50 of Acid Yellow 220 was found to be 3934 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:
no data
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:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Test Item: FAT 20049/A
Purity: approx. 89 %
Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals or test system and environmental conditions:
The compound was tested on 40 Tif. RAI rats(20 males/20 females), Animals were bred under SPF conditions in the breeding unit of the testing laboratory. They were 6 to 7 weeks old and weighed 160 to 180 g. The males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5 in a room kept at a constant temperature of 22±1°C and a relative humidity of approximately 50 %. They received water and food (NAFAG, Gossau SG, rat food) ad libitum. The rats were starved during one night before starting dose administration.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
DOSAGE PREPARATION:
The test substance was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 20 and 30% with carboxymethylcellulose 2% and administered by oral intubation. Before administration the suspension was homogeneously dispersed with an Ultra-Turrax and during administration it was kept stable with a magnetic stirrer.
Doses:
2150, 3590, 4640 and 6000 mg/kg bw
No. of animals per sex per dose:
Five/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration (mortality and clinical signs): 14 d
- Necropsy: Yes; performed on dead and killed animals
Statistics:
The LD50 including the 95 % confidence limits were calculated by probit analysis method (Goulden A (1960), Methods of Statistical Analysis, John Wiley and Sons, 3rd printing, pages 404-408).
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 934 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 542 - <= 4 368
Mortality:
A dose dependent increase in mortality was observed. No mortality was noted at the lowest dose, 3/10 and 8/10 animals died at the two subsequent intermediate dose levels respectively and all the animals (10/10) died at the highest dose level.
Clinical signs:
Within 2 h after treatment, all the animals irrespective of dosage groups showed sedation, dyspnoea, curved position and ruffled fur. Additionally in the two highest dosage groups diarrhoea was observed. The surviving animals recovered within 8 to 9 d.
Body weight:
not examined
Gross pathology:
No substance related gross organ changes were seen.
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance was found to be 3934 mg/kg bw in rats.
Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test substance (at ca. 89 % purity) following a method comparable to OECD Guideline 401. Four groups of fasted Tif: RAI rats (5/sex/dose) received the test substance at 2150, 3590, 4640 and 6000 mg/kg bw once by oral gavage. All the animals were observed for mortality and clinical signs for an observation period of 14 d. A dose dependent increase in mortality was observed. No mortality was noted at the lowest dose, 3/10 and 8/10 animals died at the two subsequent intermediate dose levels respectively and all the animals died at the highest dose level. Within 2 hours of treatment, the rats in all groups showed sedation, dyspnoea, curved position and ruffled fur. Additionally, diarrhoea was observed in the two highest dose levels. The surviving animals recovered within 8 to 9 d. Macroscopic post-mortem changes were absent. Hence based on the findings of the study, the oral LD50 of the test substance was found to be 3934 mg/kg bw (i.e.ca. 3501 mg a.i./kg bw) in rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 934 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
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

A couple of studies investigating the acute oral toxicity of Acid Yellow 220 are available which were conducted with a methodology similar to OECD Guideline 401.

In the study designated as key, 4 groups of fasted Tif: RAI rats (5/sex/dose) received the test substance at 2150, 3590, 4640 and 6000 mg/kg bw once by oral gavage. No mortality was noted at the lowest dose, 3/10 and 8/10 animals died at the two subsequent intermediate dose levels respectively and all the animals died at the highest dose level. Hence, the oral LD50 of the test substance was found to be 3934 mg/kg bw (i.e. ca 3501 mg a.i./kg bw) in rats.

In the supporting study (1984), conducted with FAT 20049/D (purity: 22.5 %), a group of Tif: RAI rats (5/sex/dose) received the test substance at 5000 mg/kg bw once by oral gavage. No mortality was observed during the observation period. hence, the LD50 value for FAT 20049/D was considered to be >5000 mg/kg bw (>1125 mg a.i./kg bw).

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Acid Yellow 220 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>250 °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 182 g/L, hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus present in the respiratory tract, thereby further limiting the absorption. Further results of exposure to test animals from the acute toxicity studies via oral route with Acid Yellow 220 indicated low toxicity potential and no classification was needed for acute toxicity or STOT SE. Taking into consideration the above arguments, no elevated toxicity other than already seen in acute oral toxicity studies is expected via the inhalation route and safety for human health can be estimated using the principles of route to route extrapolation. Hence, the conduct of acute toxicity study via inhalation route for Acid Yellow 220 is considered to be scientifically not necessary.

Dermal:

Currently no study to assess toxicity of Acid Yellow 220 on acute dermal exposure is available. However, the molecular weight of the substance is 1183.73 g/mol, which indicates the substance being too large for dermal absorption. Further, high water solubility (182 g/L) indicates the substance being highly hydrophilic. Hence, the dermal uptake for the substance is expected to be low. Further results of exposure to test animals from the acute toxicity studies via oral route indicated low toxicity potential and no classification was needed for acute toxiciy or STOT SE. Taking into consideration the above arguments, no elevated toxicity other than already seen in acute oral toxicity studies is expected via the dermal route and safety for human health can be estimated using the principles of route to route extrapolation. Similarly, absence of systemic toxicity or mortality in skin irritation as well as sensitization studies with Acid Yellow 220, further supports the conclusion that no additional adverse effects other than seen in acute oral toxicity studies are expected via dermal route. Hence, the conduct of acute toxicity study via dermal route for Acid Yellow 220 is considered to be scientifically not necessary.

Justification for classification or non-classification

Based on the available acute oral toxicity studies with Acid Yellow 220 no classification is needed under Regulation (EC) No. 1272/2008 (CLP).