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Administrative data

Description of key information

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

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

Acute inhalation: waiver

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 1991-07-11 to 1991-07-25
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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
During the acclimation period the temperature rose above the range 19-25°C on several occasions, a maximum temperature of 33°C being recorded on one occasion.
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
UK GLP (inspection date: 1990-06-19 / signature date: 1990-10-05)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent
- Age at study initiation: 5-7 weeks
- Weight at study initiation: M: 110 to 129 g; F: 119 to 127
- 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: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C/ During the acclimatisation period the temperature rose above this range on several occasions, a maximum temperature of 33°C being recorded on one occasion.
- Humidity (%): 42-62 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: not justified
- Lot/batch no. (if required): no data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Assess to food was permitted immediately after dosing
- 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, 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.
Statistics:
not done
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred throughout the study
Clinical signs:
other: No clinical signs were observed throughout the study
Gross pathology:
The necropsy findings were consistent with the background macroscopic pathology of this strain of rats:
- Urinary bladder: contained white waxy plug in 1M
- Left eye: appeared small, palpebral fissure reduced in size in 1M
- Uterus: minimally distended with fluid in 1F
Other findings:
None

No other information

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50Combined > 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, 5-7 weeks old, Crl:CD(SD) rats (5/sex) were administered a single oral dose of 2000 mg test material/kg bw by gavage. 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. No abnormality was revealed at autopsy.

 

Oral LD50Combined > 2000 mg/kg bw

 

Under the test conditions, the test material 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 key study is GLP compliant and of high quality (Klimisch score = 1).

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:
From 1991-07-18 to 1991-08-01
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 with acceptable restrictions: the % area exposed is not mentioned.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
% area exposed not mentioned
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
Inspected on 19 June 1990. Signed on 5 October 1990.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate Kent
- Age at study initiation: 10-11 weeks
- Weight at study initiation: M: 249-266 g; F:230-245g
- 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: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 °C
- Humidity (%): 55-65 %
- 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: no data
- Type of wrap if used: pad of surgical gauze 4 plies thick overlaid with a strip of aluminium foil and secured in position by a length of 5.0 cm wide 'Elastoplast' elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
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, abdominal and visceral cavities, and examination of the major organs. Abnormal tissues and organs were preserved in buffered formol saline.
Statistics:
none
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/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: Peri-nasal staining was noted in most animals, onset and recovery occurring earlier in males than in females. Piloerection was also observed in 4 males and 1 female, lasting from one to 5 days.
Gross pathology:
The necropsy findings were consistent with the background macroscopic pathology of this strain of rats:
- Thyroid: reddened appearance in 1 animal (1M)
- Thymus: reddened appearance in 4 animals (2M, 2F)
- Urinary bladder: distended with fluid in 1M and contained white waxy plug in 3M
Other findings:
None

no other information

Interpretation of results:
GHS criteria not met
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 test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs including dermal reactions and body weight for 14 days and then necropsied for macroscopic observations.

 

No mortality occurred during the study. There was no adverse effect on bodyweight gain.

Peri-nasal staining was noted in most animals, onset and recovery occurring earlier in males than in females. Piloerection was also observed in 4 males and 1 female, lasting from one to 5 days. These effects, considered as mild, were fully reversible. Therefore the test material was considered to be essentially non-toxic at 2000 mg/kg bw.

 

Dermal LD50Combined > 2000 mg/kg bw

Under the test conditions, the test material 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 key study is GLP compliant and of high quality (Klimisch score = 1).

Additional information

Acute toxicity: oral

A key study was identified (Safepharm, 1992, 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 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. No abnormality was revealed at autopsy. 

Oral LD50 Combined > 2000 mg/kg bw.

Acute toxicity: dermal

A key study was identified (Toxicol, 1991, 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 test material at the dose of 2000 mg/kg bw.

No mortality occurred during the study. There was no adverse effect on bodyweight gain.

Peri-nasal staining was noted in most animals, onset and recovery occurring earlier in males than in females. Piloerection was also observed in 4 males and 1 female, lasting from one to 5 days. These effects, considered as mild, were fully reversible. Therefore the test material was considered to be essentially non-toxic at 2000 mg/kg bw.

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 (< 0.04 Pa at 25°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 = 5.52 at 25°C - from analogue, WS = 0.9 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 (Oral):

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 the LD50 is higher than 2000 mg/kg bw and the substance does not meet the specific criteria for the Category 5 defined in the GHS.

Acute toxicity (Dermal):

The substance is:

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

- not classified according to the GHS as the dermal LD50 is higher than 2000 mg/kg bw and the substance does not meet the specific criteria for the Category 5 defined in the GHS.

Acute toxicity (Inhalation):

No information 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 required.

Specific target organ toxicity: single exposure (Inhalation):

No information was available.

Aspiration hazard:

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