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Description of key information

Acute Oral Toxicity:

An acute oral toxicity study in female Wistar rat was carried out with FAT 66042/A according to OECD guideline 423 and EU method B.1. Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a dosing volume of 10 ml/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Soft feces were recorded in one animal at the 3-hour observation. Otherwise, no clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose (LD50) of FAT 66042/A after single oral administration to female Wistar rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Acute Inhalation Toxicity:

Currently no study to assess acute inhalation toxicity of Stilbene optical brightener is available.However, low vapour pressure owing to high melting point (>350 °C), the substance is considered to have low volatility. Synthesis 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. The chemical showed low toxicity potential in the available acute oral (LD50>2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified as STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure ofStilbene optical brightenervia inhalation route.

Acute Dermal Toxicity:

Currently no study to assess the acute dermal toxicity of Stilbene optical brightener is available. However, it has water solubility of 380 g/L and n-octanol/water partition coefficient (log P) of -3.392, indicating it being too hydrophilic to cross the lipid rich environment of thestratum corneum. Synthesis 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 (LD50>2000 mg/kg bw), with no mortality or systemic toxicity, hence it does not need to be classified as STOT SE.Similarly, absence of local toxicity in eye and skin irritation studies as well as absence of systemic toxicity in sensitization studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Stilbene optical brightener 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:
30 April to 23 May 2008.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17th December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
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 number of test material: 0582900
- Expiration date of the lot/batch: 25-FEB-2013

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5 °C, light protected.
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCCLtd Laboratory Animal Services Wölferstrasse 4 4414 Füllinsdorf / Switzerland
- Animals: rat, HanRcc: WIST(SPF).
- Age at study initiation: 11 weeks.
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz, Switzerland) .
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 12/08 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum.
- Water: community tap water from Füllinsdorf ad libitum.
- Acclimation period: under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C, continuously monitored.
- Humidity: between 30-70 % (values above 70 % during cleaning process possible).
- Air changes: 10-15 air changes per hour.
- Photoperiod: light cycle of 12 hours light and 12 hours dark.
- Other: music during the daytime light period.
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on oral exposure:
VEHICLE
- Vehicle: polyethylene glycol 300 (PEG 300)
- Justification for choice of vehicle: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the statement of compliance.
- Lot/batch no.: 1310049

DOSE FORMULATION
The dose formulations were made shortly before each dosing occasion using a magnetic stirrer, a spatula and/or an Ultra-Turrax (Janke & Kunkel, D-79219 Staufen) as homogenizers.
The test item was weighed into a tarred glass beaker on a suitable precision balance and the vehicle added (weight:volume).
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
The test item was diluted in vehicle at a concentration of 0.2 g/ml and administered at a dosing volume of 10 ml/kg.

TREATMENT
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 17 to 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
The dosing volume was 10 ml/kg body weight.
Doses:
Single dose at 2000 mg/kg bw.
No. of animals per sex per dose:
3 females per group; two groups tested.
Control animals:
no
Details on study design:
OBSERVATIONS
- Duration of observation period following administration: 15 days
- Mortality / Viability: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
- Body Weights: on test days 1 (prior to administration), 8 and 15.
- Clinical Signs: daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy: all animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Statistics:
No statistical analysis was used.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
other: Soft feces were recorded in one animal at the 3-hour observation. Otherwise, no clinical signs were observed during the course of the study.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Mortality / Clinical Signs

Dose mg/kg bw Animal N. Sex Signs Test days
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
0.5 1 2 3 5
2000 1 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √
2 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √
3 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √
2000 4 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √
5 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √
Soft feces √
6 F No clinical signs √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √ √

Key:  √ noted

* Examinations were performed within the first 30 minutes and 1, 2,3 and 5 hours after treatment.

No clinical signs were evident in any animal during the acclimatization period.

Macroscopical findings (scheduled necropsy, 21 May-08, day 15 after treatment)

Group 1:

Animal 1: no findings noted

Animal 2: no findings noted

Animal 3: no findings noted

Group 2:

Animal 4: no findings noted

Animal 5: no findings noted

Animal 6: no findings noted

Interpretation of results:
GHS criteria not met
Conclusions:
The oral median lethal dose (LD50) of FAT 66042/A in female rat is greater than 2000 mg/kg body weight.
Executive summary:

An acute oral toxicity study in female Wistar rat was carried out with FAT 66042/A according to OECD guideline 423 and EU method B.1. Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a dosing volume of 10 ml/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality / viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. Soft feces were recorded in one animal at the 3-hour observation. Otherwise, no clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose (LD50) of FAT 66042/A after single oral administration to female Wistar rats, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP compliance and OECD 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
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the observed LD50 of >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.