Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 423, 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 1999-04-27 to 1999-05-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 423 and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996
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:
yes (incl. certificate)
Remarks:
UK GLP Compliance Program (inspection date 1998-03-23)
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: Sprague-Dawley CD (Crl : CD®(SD) IGS BR)
- Source: Charles River (UK) Limited, Margate Kent, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: M: 210 to 217 g; F: 208 to 222 g
- Fasting period: overnight before dosing and for approximately 2 hours after dosing.
- Housing: in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diets Services, Witham, Essex).
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): approximately 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN LIFE DATES:
From 1999-04-27 to 1999-05-13
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
Not applicable

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw
The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on available information
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females first, followed by 3 males
Control animals:
no
Details on study design:
- Dosing: animals were dosed once
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: approximately 30 minutes, 1, 2 and 4 hours after dosing and thereafter daily for 14 consecutive days.
Weighing: prior to dosing, 7 and 14 days after treatment.
- Necropsy of survivors performed: yes, external examination and opening of the abdominal and thoracic cavities for examination of major organs.
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:
There were no deaths
Clinical signs:
Ataxia and/or hunched posture was noted in all animals two to four hours after dosing with hunched posture still apparent in all females one day after dosing. Male animals recovered one day after dosing and female animals recovered two days after dosing.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
none

no other information

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

In an acute oral toxic class method study performed according to the OECD test guideline No. 423 and in compliance with GLP, undiluted ST 08 C 98 was tested using a stepwise procedure. Using all available information, 2000 mg/kg bw was selected as the starting dose. In a first step, a group of three fasted Sprague-Dawley CD (Crl : CD®(SD) IGS BR) females rat was treated with the starting dose of 2000 mg/kg bw by gavage. In the absence of compound-related mortality, dosing of three additional fasted males was performed at the same dose level.

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

There were no deaths during the study. Clinical signs of systemic toxicity noted were ataxia and/or hunched posture. Male animals recovered one day after dosing and female animals recovered two days after dosing. All animals showed expected gains in bodyweight over the study period and no abnormality was noted at necropsy.

Oral LD50 Combined > 2000 mg/kg bw

Under the test conditions, ST 08 C 98 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
Value:
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 registered substance has a low vapour pressure (0.053 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 = 4.46 at 25°C, WS = 11.6 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 2000-09-14 to 2000-10-07
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:
Directive 88/320/CEE (Inspected on 1999-09-22)
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: Sprague-Dawley ICO: OFA-SD (lOPS Caw)
- Source: Iffa Credo, 69210 L'Arbresle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: of 265 ± 11 g for the Males and 218 ± 8 g for the Females
- Fasting period before study: no
- Housing: housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm).
- Diet (e.g. ad libitum): free access to A04 C pelleted diet (DAR, 91360 Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±2
- Humidity (%):30 to 70
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: until 2000-09-28
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% (5 cm x 6 cm for the females and 5 cm x 7 cm for the males) of the body surface of the animals
- Type of wrap if used: hydrophilic gauze pad held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done, no residual test substance was observed at removal of the dressing.
- Time after start of exposure: not applicable

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): taking into consideration the specific gravity of 1.0091 g/mL
Duration of exposure:
24 hours
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 and mortality: frequently during the hours following administration of the test substance. Thereafter, at least once a day until day 15.
Weighing: prior to administration of the test substance on day 1 and then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight
- Necropsy of survivors performed: yes. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.
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:
No clinical signs and no cutaneous reactions were observed during the study.
Body weight:
A reduced body weight gain was seen in 4/5 females between day 1 and day 8. The overall body weight gain of the other animals was similar to that of CIT historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
None

no other information

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 test guideline No. 402 and in compliance with GLP, groups of 8-week old Sprague-Dawley rats (5/sex)were exposed to undiluted ST 32 C 99 at dose of 2000 mg/kg bw. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of ST 32 C 99. All animals were subjected to necropsy.

 

No clinical signs and no deaths were observed during the study. A reduced body weight gain was seen in 4/5 females between day 1 and day 8. The overall body weight gain of the other animals was similar to that of CIT historical control animals. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy in any animal.

Dermal LD50Combined > 2000 mg/kg bw

Under the test conditions, ST 32 C 99 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 dermal toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
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 (Safepharm, 1999, rel. 1). In this acute oral toxic class method study performed according to the OECD test guideline No. 423 and in compliance with GLP, undiluted ST 08 C 98 was tested using a stepwise procedure. Using all available information, 2000 mg/kg bw was selected as the starting dose. In a first step, a group of three fasted Sprague-Dawley CD (Crl : CD®(SD) IGS BR) females rat was treated with the starting dose of 2000 mg/kg bw by gavage. In the absence of compound-related mortality, dosing of three additional fasted males was performed at the same dose level.

There were no deaths during the study. Clinical signs of systemic toxicity noted were ataxia and/or hunched posture. Male animals recovered one day after dosing and female animals recovered two days after dosing. All animals showed expected gains in bodyweight over the study period and no abnormality was noted at necropsy.

Oral LD50 Combined > 2000 mg/kg bw

 

Acute toxicity: dermal

A key study was identified (CIT, 2000, rel. 1). In this limit acute dermal toxicity study performed according to the OECD test guideline No. 402 and in compliance with GLP, rats were exposed to undiluted ST 32 C 99 at dose of 2000 mg/kg bw. The test site was then covered by a semi-occlusive dressing for 24 hours.

No clinical signs and no deaths were observed during the study. A reduced body weight gain was seen in 4/5 females between day 1 and day 8. The overall body weight gain of the other animals was similar to that of CIT historical control animals. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy in any animal.

Dermal LD50 Combined > 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 registered substance has a low vapour pressure (0.053 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 = 4.46 at 25°C, WS = 11.6 mg/L at 20°C).

Justification for classification or non-classification

Harmonised classification:

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

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

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

- not classified according to the GHS as the LD50 is not expected to be in the range 2000 -5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the test item is:

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

- not classified according to the GHS as the LD50 is not expected to be in the range 2000 -5000 mg/kg bw.

Acute toxicity via Inhalation:

No data was 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.