Registration Dossier

Administrative data

Description of key information

- Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 401, GLP, K, rel. 1)
- Acute toxicity: dermal: LD50 > 2000 mg/kg bw (OECD 402, GLP, K, rel. 1)
- Acute toxicity: inhalation: waiving

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:
From 1994-04-27 to 1994-05-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 401 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Program (inspection date: 1992-10-27 / signed on: 1992-012-04)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Remarks:
Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: approximately 100 g
- Fasting period before study: overnight before dosing
- Housing: in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays.
- Diet: pelleted diet ad libitum (SQC rat and mouse maintenance No. 1 Expanded, produced by Special Diets Services, Witham, Essex).
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 36-62 %
- Air changes (per hr): no data, air conditioned room
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: delivered on 1994-05-22 for the range-finding study and 1994-04-29 from the main study
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
Range-finding test: 25, 50 and 100 mg/mL
main test: 100 mg/mL

DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
Range-finding test: 500, 1000 and 2000 mg/kg bw
Main test: 2000 mg/kg bw
No. of animals per sex per dose:
Range-finding test: 2 animals/sex/dose
Main test: 5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: approximately 30 minutes, 1, 2 and 4 hours afters dosing and thereafter for a further 7 days in the range finding study and 14 days in the main study.
Weighing: on the day of dosing, on days 8 and 15.
- Necropsy of survivors performed: yes, including opening of the thoracic and visceral cavities, opening and examination of the stomach and representative sections of the gastro-intestinal tract and examination of the major organs. Abnormal tissues and organs were preserved in buffered formol saline. Necropsy was not performed on range-finding animals.
Statistics:
none
Preliminary study:
No deaths occurred and no signs of toxicity were exhibited by any animal in any dose group in the range-finding study
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred.
Clinical signs:
All animals maintained a healthy appearance throughout the 15 day observation period.
Body weight:
There was no adverse effect on bodyweight gain in animals of either sex.
Gross pathology:
At necropsy, the submandibular lymph nodes were enlarged and the urinary bladder was distended with fluid in one male. The thymus was red and swollen in one female. No abnormalities were detected in the remaining animals.
Other findings:
none

none

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 Combined > 2000 mg/kg bw
Executive summary:

In a limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, groups of fasted, 4 -6 weeks old, Crl:CD(SD) rats (5/sex) were administered a single oral dose of ST 06 C 93 diluted in water at 2000 mg/kg bw by gavage. This limit dose was selected based on the absence of mortality and clinical signs in 2 animals/sex/dose (500, 1000 or 2000 mg/kg bw) in the range-finding study.

The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. At necropsy, the submandibular lymph nodes were enlarged and the urinary bladder was distended with fluid in one male. The thymus was red and swollen in one female. No abnormalities were detected in the remaining animals.

 

Oral LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, ST 06 C 93 is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score = 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the substance has a low vapour pressure (17.23 Pa at 20°C) and a low freezing point (<-20°C), so the potential for the generation of inhalable forms is low. Dermal exposure is the more likely route of exposure based on physico-chemical properties (Log Kow = 4.68 at 22.5°C, WS = 4.7 mg/L at 20°C).
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:
From 1995-02-08 to 1995-02-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 402 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP compliance programme (inspection date: 1992-10-27)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Storage conditions: 4 °C in the dark
Species:
rat
Strain:
Crj: CD(SD)
Remarks:
Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent
- Age at study initiation: 9-10 weeks
- Weight at study initiation: approximately 200 g
- Fasting period before study: no
- Housing: individually housed in grid bottomed cages suspended over cardboard lined excreta trays.
- Diet (e.g. ad libitum): pelleted rodent diet ad libitum (SQC Rat and Mouse Maintenance Diet No. 1 Expanded, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 31-62 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: on the back
- % coverage: 10 %
- Type of wrap if used: gauze was covered with a strip of aluminium foil. The trunk of each animal was encircled with a length of 5 cm wide non-irritant surgical tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): determined from the individual bodyweight of each animal
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: approximately 30 minutes, 1, 2 and 4 hours afters dosing and thereafter for 14 consecutive days.
Weighing: on the day of dosing, on days 8 and 15.
- Necropsy of survivors performed: yes, including opening of the thoracic and visceral cavities, and opening and examination of the stomach and representative sections of the gastro-intestinal tract and examinations of the major organs. Abnormal tissues and organs were preserved in neutral buffered formaldehyde but were not processed further.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
All animals maintained a healthy appearance throughout the 15 day observation period. A scab was noted on the head of one male on Day 15 but this was not considered to be treatment related.
Body weight:
There was no adverse effect on bodyweight gain in animals of either sex.
Gross pathology:
At necropsy, moderate pelvic dilation of the right kidney and swelling of the left submandibular lymph node were noted on one animal. No abnormalities were detected in the remaining animals.
Other findings:
None

None

Interpretation of results:
not classified
Conclusions:
Dermal LD50Combined > 2000 mg/kg bw
Executive summary:

In a limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, groups of young adult Crl:CD(SD) rats (5/sex) were occlusively exposed to undiluted ST 06 C 93 at a dose level of 2000 mg/kg bw. After a contact period of 24 h, the dressings were removed and the treated skin cleansed with water. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No deaths occurred during the study. All animals maintained a healthy appearance throughout the 15 day observation period. A scab was noted on the head of one male on Day 15 but this was not considered to be treatment related. There was no adverse effect on bodyweight gain in animals of either sex. At necropsy, moderate pelvic dilation of the right kidney and swelling of the left submandibular lymph node were noted on one animal. No abnormalities were detected in the remaining animals. 

 

Dermal LD50Combined > 2000 mg/kg bw

 

Under the test conditions, ST 06 C 93 is not classified according to the the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and of high quality (Klimisch score = 1).

Additional information

Acute toxicity: Oral :

A key study was identified (Toxicol, 1994, rel. 1). In this limit acute oral toxicity study performed according to the OECD test guideline No. 401 and in compliance with GLP, rats were administered a single oral dose of ST 06 C 93 diluted in water at 2000 mg/kg bw by gavage. No mortality and no clinical signs were observed throughout the study. There was no adverse effect on bodyweight gain. At necropsy, the submandibular lymph nodes were enlarged and the urinary bladder was distended with fluid in one male. The thymus was red and swollen in one female. No abnormalities were detected in the remaining animals.

Oral LD50Combined > 2000 mg/kg bw

Acute toxicify: Dermal:

A key study was identified (Toxicol, 1995, rel. 1). In this limit acute dermal toxicity study performed according to the OECD guideline No. 402 and in compliance with GLP, rats were occlusively exposed to undiluted ST 06 C 93 at a dose level of 2000 mg/kg bw. No deaths occurred during the study. All animals maintained a healthy appearance throughout the 15 day observation period. A scab was noted on the head of one male on Day 15 but this was not considered to be treatment related. There was no adverse effect on bodyweight gain in animals of either sex. At necropsy, moderate pelvic dilation of the right kidney and swelling of the left submandibular lymph node were noted on one animal. No abnormalities were detected in the remaining animals. 

Dermal LD50Combined > 2000 mg/kg bw

Acute toxicity: Inhalation:
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the substance has a low vapour pressure (17.23 Pa at 20°C) and a low freezing point (<-20°C), so the potential for the generation of inhalable forms is low. Dermal exposure is the more likely route of exposure based on physico-chemical properties (Log Kow = 4.68 at 22.5°C, WS = 4.7 mg/L at 20°C).

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 (CLP).

Self-classification:

Acute toxicity (Oral route):

Based on the available information, the substance is:

- not classified according to the CLP as the LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS as there is neither mortality nor significant clinical signs of toxicity when tested up to Category 4 values.

Acute toxicity (Dermal route):

Based on the available information, the substance is:

- not classified according to the CLP as the LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS as there is neither mortality nor significant clinical signs of toxicity when tested up to Category 4 values.

Acute toxicity (Inhalation):

This information is not available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available. However, the registered substance is not a skin or an eye irritant, therefore respiratory tract irritation is not expected.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.