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Administrative data

Description of key information

The acute oral LD50 of FAT 40554 in rats is greater than 5000 mg/kg and the acute dermal LD50 in rabbits is greater than 2000 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:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None
Reference:
Composition 1
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River U.K. Ltd., Margate, kent, England.- Age at study initiation: 7 weeks old approximately- Weight at study initiation: 160 g - 197 g- Housing: HRC cage type 5 - cages with wire mesh floors - Diet (e.g. ad libitum): standard laboratory rodent diet (Biosure LAD 1) ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: 7 days prior to the start of the main studyENVIRONMENTAL CONDITIONS- Temperature (°C): 21°C - 23°C- Humidity (%): 44 %H- Air changes (per hr): 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hour period
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
None
Doses:
5000 mg / kg bodyweight
No. of animals per sex per dose:
10 (5 males & 5 females)
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 14 days - Frequency of observations and weighing: day 1, 8 & 15- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: macroscopic appearance eaxmined
Statistics:
None
Preliminary study:
The results of the preliminary study indicated that the acute lethal dose to male and female rats of D-523 was greater than 2.5 g/kg bodyweight.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths following a single oral dose of D-523 at 5.0 g/kg bodyweight.
Clinical signs:
Signs of toxicity related to dose levels:Piloerection was noted in all rats within 5 minutes of dosing and throughout day 1. All animals showed the expected gains in bodyweight over the study period.
Body weight:
Slightly low bodyweight gains were recorded on Day 15 for one male and 4 females; these animlas achieved anticipated gains on Day 8. All other rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Terminal autopsy revealed no macroscopic abnormalities for the majority of rats. Unilateral hydronephrosis was apparent for one male on Day 15. A slow incidence of this abnormality occurs spontaneously among untreated rats of the CD starin at this laboratory, the finding was not considered to be related to treatment.
Other findings:
None

INDIVIDUAL BODUWEIGHT CHANGES (g) OF RATS DOSED WITH D-523:

Sex Dose (g/kg) Animal number & ear mark Bodyweight gains (g) at
Week 1 Week 2
Male 5 1 RP 76 50
2LP 90 66
3RPLP 100 74
4RIRO 95 63
5LILO 90 56
Female 5 6RP 54 8
7LP 58 16
8RPLP 37 4
9RIRO 36 9
10LILO 61 1
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results of the main study indicated that the acute lethal dose to male and female rats of FAT 40554 was greater than 5000 mg/kg bodyweight.
Executive summary:

The aim of this study was to determine the acute oral toxicity potency of FAT 40554 in rats after single administartion by oral gavage.

This experiment was performed according to the EU Method B.1 (Acute Toxicity (Oral))

The test was performed on rats (5 males and 5 females) per dose level, at one dose level: 5000 mg/kg.

The test material was dissolved in distilled water.

The observation period was 14 days or until all symptoms have disappeared, whichever lasts longer.

Mortality:

No mortality occured during the experiment.

Body weight:Normal weight gain.

Signs of toxicity: Piloerection was noted in all rats within 5 minutes of dosing and throughout day 1. All animals showed the expected gains in bodyweight over the study period.

Effects in organs: Terminal autopsy revealed no macroscopic abnormalities for the majority of rats. Unilateral hydronephrosis was apparent for one male on Day 15. A slow incidence of this abnormality occurs spontaneously among untreated rats of the CD starin at this laboratory, the finding was not considered to be related to treatment.

In conclusion, the median lethal dose is found to be greater than 5000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

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:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
None
Reference:
Composition 1
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
None
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
None
Species:
rat
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles river Japan- Age at study initiation: 6 weeks old- Weight at study initiation: 243 to 272g for males & 156 to 173g for females- Housing: rectangular suspension cage with a stainless steel wire mesh floor- Diet (e.g. ad libitum): laboratory animal chows (CRF-1, sterilised by CO irradiation, Oriental Yeast Co. Ltd.) ad libitum- Water (e.g. ad libitum): free access to tap water ad libitum- Acclimation period: 8 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 24+-2°C- Humidity (%): 55+-10%- Air changes (per hr): 10 times per hour- Photoperiod (hrs dark / hrs light): fluorescent lighting system - 12 hours light/dark cycle
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
The suspension was spread over the shreaded area (30 cm2) using a plastic syringe (2.5ml) and an attached gastric metal probe with a plastic tip (1.2 mm in diameter, 80 mm in length) at the dosing volume of 10 ml/lg body weight. The treated area was then covered with surgical tape to prevent the animals from licking the test material from the treated area.
Duration of exposure:
24 hours
Doses:
The test material was suspended in 0.5% methylcellulose aqueous solution (MC) at the concentration of 200 mg/ml.
No. of animals per sex per dose:
5 animals per group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: 1, 2 and 4 hours after administration on the first day and once daily for 2 weeks thereafter- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
The mortality and LD50 values were calculated.
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the animals
Clinical signs:
No abnormal signs were observed.
Body weight:
There was no difference in the mean body weight and the mean body weight gain between treated groups and the control group at every determination.
Gross pathology:
Retention of white substances in the urinary bladder (male) and distended uterine horns with fluid retention were found in several animals including controls. These changes have been occasionally found in untreated rats in this laboratory.No skin irritative reaction was observed at the application site. Therefore, no remarkable change related to the administration of the test material was found.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, FAT 40554 did not show acute dermal toxicity.
Executive summary:

An acute dermal toxicity test of D-523 was examined in rats according to EU Method B.3 (Acute Toxicity (Dermal).

5 animals per group were administered the suspension with a dose of 200 mg/ml in 0.5% methylcellulose aqueous solution (MC).

Neither abnormal signs nor dead animals were found in any group among animals of either sex, and the acute dermal LD50 value for both males and females was estimated to be greater than 2000 mg/kg body weight.

The body weight was not affected by the administration of the test material. In gross pathology, there was neither a remarkable change related to the test material nor a skin irritative reactions at the application site in any animal.

Therefore, the FAT 40554 did not show any acute dermal toxicity in animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute Oral Toxicity:

A key study was performed to determine the acute oral toxicity potency of FAT 40554 in rats after single administartion by oral gavage.

This experiment was performed according to the EU Method B.1 (Acute Toxicity (Oral).

No mortality occurred during the experiment with normal weight gain. Piloerection was noted in all rats within 5 minutes of dosing and throughout day 1. All animals showed the expected gains in bodyweight over the study period. Terminal autopsy revealed no macroscopic abnormalities for the majority of rats. Unilateral hydronephrosis was apparent for one male on Day 15. A slow incidence of this abnormality occurs spontaneously among untreated rats of the CD strain at this laboratory, the finding was not considered to be related to treatment.

In conclusion, the median lethal dose is found to be greater than 5000 mg/kg bodyweight.

Acute Dermal Toxicity:

An acute dermal toxicity of D-523 was examined in rats according to EU Method B.3 (Acute Toxicity (Dermal).

5 animals per group were administered the suspension with a dose of 200 mg/ml in 0.5% methylcellulose aqueous solution (MC).

Neither abnormal signs nor dead animals were found in any group among animals of either sex, and the acute dermal LD50 value for both males and females was estimated to be greater than 2000 mg/kg body weight. The body weight was not affected by the administration of the test material. In gross pathology, there was neither a remarkable change related to the test material nor a skin irritative reactions at the application site in any animal.

Therefore, the FAT 40554 did not show any acute dermal toxicity in animals.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study

Justification for selection of acute toxicity – dermal endpoint
Non GLP guideline study

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).