Registration Dossier

Administrative data

Description of key information

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:
14th to 30th September 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in a GLP compliant laboratory according to accepted regulatory guidelines
Qualifier:
according to
Guideline:
other: Annex V (Acute toxic class)
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Reputable commercial supplier
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 225-231g (males) and 201-206g (females)
- Fasting period before study: overnight before dose administration and for 3-4 hours after dose administration
- Housing: solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): free access (Rat and Mouse Expanded Diet No.1)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25C
- Humidity (%): 30-70%
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): Not stated

IN-LIFE DATES: From: To: 14-30th September 1999
Route of administration:
oral: gavage
Vehicle:
other: Arachis oil BP.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve in distilled water or other aqueous vehicles.
- Lot/batch no. (if required): N/a
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual): Not unusual

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The information available suggested a starting dose of 2000 mg/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were observed for deaths or overt signs of toxicity \12, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: no
- Other examinations performed: All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No signs of systemic toxicity were noted during the study period.


All animals showed expected gains in bodyweight over the
study period.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs:
No abnormalities were noted at necropsy of animals killed at the end of the study period.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose, (LD50) of the test material, S-900, in the SpragueDawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
No mortalities were noted at 2000 mg/kg bodyweight.
No symbol and risk phrase are required according to EU labelling regulations.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted in a GLP compliant laboratory according to accepted regulatory guidelines

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:
26th October to 9th November 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in a GLP compliant laboratory according to accepted regulatory guidelines
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: REPUTABLE COMMERCIAL SUPPLIER
- Age at study initiation: 8-12 weeks
- Weight at study initiation:200-221g (males); 200-222g (femailes)
- Fasting period before study: No
- Housing: The animals were housed in suspended polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25C
- Humidity (%): 30-70%
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): Not stated

IN-LIFE DATES: From: To: 26th October to 9th November 1999
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage:105 of total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution):N/a
- Constant volume or concentration used: yes
- For solids, paste formed: yes test substance already a paste

Duration of exposure:
24 h
Doses:
2000 mg/kg/body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity Yz, 1,2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: no
- Other examinations performed: Gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormal ities was recorded. No tissues were retained.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No clinical signs of toxicity were noted during the study.

All animals showed an expected gain in bodyweight during the
study.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
Effects on organs:
No abnormalities were noted at necropsy.
Other findings:
Signs of toxicity (local):
Very slight to well defined erythema was noted at the
treatment sites of all animals one day after dosing and in
four female animals two and three days after dosing. Other
skin reactions noted at the treatment sites of all female
animals were haemorrhage of the dermal capillaries and crust
formation. The treatment sites appeared normal two to seven
days after dosing.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD 5O) of the test material, S-900, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted in a GLP compliant laboratory according to accepted regulatory guidelines

Additional information

Justification for selection of acute toxicity – oral endpoint

The acute oral median lethal dose, (LD50) of the test material, S-900, in the SpragueDawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. No mortalities were noted at 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Justification for selection of acute toxicity – inhalation endpoint

The test material is a dark brown paste or viscous liquid with a measured vapour pressure of 2.0 x 10-20 Pa at 25' C (see report no 744/070 documented elsewhere in this dossier). Exposure by the inhalation route is unlikely to occur as the test material will not form a vapour and is unlikely to form droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint

The acute dermal median lethal dose (LD50) of the test material, S-900, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

The LD50 for the acute oral and acute dermal studies were both >2000 mg/kg bodyweight. with no clinical signs reported.