Registration Dossier

Administrative data

Description of key information

The oral and dermal LD50 values for Solvent Yellow 163 were considered to be >2000 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:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 188719.4
- Expiration date of the lot/batch: November 2003

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (approx. 20 °C) away from direct sunlight.
- Stability under test conditions: Stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: 24 hours at room temperature
Species:
rat
Strain:
Wistar
Remarks:
Hanlbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Females: 10 weeks, Males: 8 weeks
- Weight at study initiation: Females: 181.6-186.0 g, Males: 201.0-206.4 g
- Fasting period before study: Approx. 17.5 to 19.5 h
- Housing: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: Pelleted standard Kliba 3433, batch no. 28/98, rat maintenance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) (ad libitum except for the overnight fasting period prior to intubation)
- Water: Tap water (ad libitum)
- Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
- Identification: By unique cage number and corresponding color-coded spots on the tail.

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3 °C
- Humidity: 40-70 % (values above 70% during cleaning process possible)
- Air changes: 10-15 air changes/h
- Photoperiod: 12 h dark/12 h light cycle
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
Test substance preparation:
The test substance was placed into a glass beaker on a tared Mettler PG 503-S balance and the vehicle (polyethylene glycol) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test substance in the vehicle was maintained during treatment. The preparation was made shortly before each dosing.

Treatment
The animals received a single dose of the test substance on a mg/kg bw basis by oral (gavage) following fasting for approx. 17.5 to 19.5 h, but with free access to water. Food was provided again approx. 3 h after dosing.
Dose/kg body weight 2000 mg
Application volume / kg body weight: 10 mL
concentration: 0.2 g/mL
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Other examinations performed: Clinical signs, body weight,organ weights, histopathology, other:
-Mortality / Viability: Four times during test Day 1 and once daily during Days 2-15.
- Body weights: On test Day 1 (pre-administration), 8 and 15.
- Clinical signs: Each animal was examined for changes in appearance and behavior four times during Day 1, and once daily during Days 2-15.
- Necropsy of survivors performed: yes, at the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN at a dose of at least 2 mL/kg bw (equivalent to at least 320 mg sodium pentobarbitone/kg bw). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.
Statistics:
No statistical analysis was used as no deaths occurred.
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 920 mg/kg bw
Based on:
act. ingr.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed troughout the study period.
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance was found to be >2000 mg/kg bw (i.e. ca. >1920 mg a.i./kg bw) in rats.
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in Wistar rats according to OECD Guideline 423 and EU Method B.1. Two groups, each using three female or three male fasted rats, received a single oral (gavage) dose of 2000 mg/kg bw. The test substance was suspended in vehicle (polyethylene glycol) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically after 15 days of observation. No death occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy.

Based on the findings of the study, the oral median lethal dose (LD50) of the test substance was found to be > 2000 mg/kg bw (i.e. ca. 1920 mg a.i./kg bw) in rats.

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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of FAT 41034/A after single dermal administration to rats of both sexes, observed over a period of 14 days was greater than 2000 mg/kg bw.
Executive summary:

Currently no study to assess the acute dermal toxicity of Solvent Yellow 163 is available. However, the source substance, Disperse Red 381 was assessed for acute dermal toxicity in a study conducted according to OECD Guideline 402. In this study, a group of five male and five female HanBrl: WIST rats were treated with FAT 41'034/A at 2000 mg/kg by dermal application. The test item was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume of 4 mL/kg. The animals were examined for clinical signs four times during test day1 and once daily during the test days 2 -15. Mortality/viability was recorded together with the clinical signs at the same time intervals on the test day1. During the test days 2 -15 it was recorded two times a day. BW were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred throughout the study. Red skin and test item residuals were evident in all animals from test day 2 to days 7 or 11. Slight scales on the back were observed in two males and two feamles from test day 8 until test day 11. The bw of the animals were within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. As a conclusion, the median lethal dose of FAT 41034/A after single dermal administration to rats of both sexes, observed over a period of 14 days was 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:
Good quality GLP study

Additional information

Acute oral toxicity:

Solvent Yellow 163 was assessed for acute oral toxicity in couple of studies conducted according to OECD Guideline 423 and another study according to OECD Guideline 401. In the acute oral toxicity study, considered to be key, FAT 93450 was tested in stepwise manner in Hanlbm: WIST (SPF) rats according to OECD Guideline 423 and EU Method B.1 (Ullman and Rosemann, 1999). Two groups, each using three male or three female fasted rats, received a single oral (gavage) dose of 2000 mg/kg bw in two steps. No mortality occurred, no clinical signs were observed and no significant macroscopic abnormalities were seen at necropsy. Thus, the acute oral median lethal dose (LD50) of test substance in the rats was estimated to be >2000 mg/kg bw. Similar outcome was seen in the supporting study (1998) conducted according to OECD Guideline 423, with no mortality seen at two steps conducted a week apart at 2000 mg/kg bw. Hence, the LD50was considered to be >2000 mg/kg bw. In the standard acute oral toxicity study conducted as per OECD Guideline 401, no mortality was seen at 5000 mg/kg bw when tested with a group of 5 male and 5 female rats, hence the LD50was considered to be >5000 mg/kg bw.

Acute inhalation toxicity:

Currently no study to assess the acute inhalation toxicity potential of Solvent Yellow 163 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>350 °C). Hence the substance is considered to have low volatility. 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 a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further the chemical was found to have low acute toxicity when tested via oral route with no mortality when tested upto 5000 mg/kg bw. Hence, considering all the above arguments, it is considered that Solvent Yellow 163 has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary.

Acute dermal toxicity:

Currently no study to assess the acute dermal toxicity of Solvent Yellow 163 is available. However, the source substance, Disperse Red 381 was assessed for acute dermal toxicity in a study conducted according to OECD Guideline 402. In this study, a group, of 5 male and 5 female rats, was exposed to Disperse Yellow 381 (FAT 41034/A) at 2000 mg/kg bw for 24 hours dermally. No deaths occurred during the study. Red skin and test item residuals were evident in all animals from test day 2 to days 7 or 11. Slight scales on the back were observed in two males and two females from test day 8 until test day 11. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. Hence based on these findings, the dermal LD50 for Disperse Red 381 was considered to be >2000 mg/kg bw.

The molecular weight of Solvent Yellow 163 is 424.54 g/mol, indicating it being large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be limited. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50>5000 mg/kg bw), with no mortality or systemic toxicity being seen upto 5000 mg/kg bw, hence it does not need to be classified as STOT SE. Similarly, absence of systemic toxicity in skin irritation and sensitisation studies, further supports the conclusion that no adverse effects are expected for the chemical via the dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Taking into consideration the above arguments and the fact that the source substance Disperse Red 381 displayed low toxicity in the available acute dermal toxicity study, low toxicity is expected on acute dermal exposure of Solvent Yellow 163 as well and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

The available toxicity studies indicate that Solvent Yellow 163 should not be classified for acute toxicity according to CLP Regulation criteria.