Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 5000 mg/kg bw (similar to OECD 401 in rats, K, rel. 2).
Acute toxicity: dermal: LD50 > 2000 mg/kg bw (similar to OECD 402 in rabbits, K, rel. 2).

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 February 11 to 25, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: GLP study comparable to OECD TG 401.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
other: Section 1500.3 - Federal Hazardous Substances Act Regulations - 16 CFR
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
environmental conditions not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sherman-Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200-300 g
- Fasting period before study: Animals were fasted overnight before dosing.
- Diet: Food, ad libitum
- Water: Water, ad libitum

IN-LIFE DATES: From: February 11, 1981 To: February 25, 1981.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data
Doses:
5000 mg/kg bw
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:
Animals were observed for mortality and clinical signs daily for 14 days. Initial and final bodyweights of animals were recorded.
- Necropsy of survivors performed: Yes; animals were subjected to gross necropsy.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 2/5 males and 1/5 female were died within 24 h of dosing.
Mortality:
- 2/5 males and 1/5 females were died within 24 h of dosing.
Clinical signs:
- Animals were depressed, ruffled and dirty within 3-4 h of dosing.
- After 5-6 h several animals were severely depressed or semicomatose.
- Surviving animals remained in generally poor health for 4-5 days before recovering.
Body weight:
- All animals showed expected gains in bodyweight over the 14-day study period.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 Combined > 5000 mg/kg bw
Executive summary:

In an acute oral toxicity study (limit test), performed similarly to OECD Guideline No. 401, a group of Sherman-Wistar rats (5/sex) were administered a single oral dose of test material at 5000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

 

2/5 males and 1/5 females were died within 24 h of dosing. Animals were depressed, ruffled, dirty within 3 -4 h of dosing and severely depressed or semicomatose after 5-6 h of dosing. Surviving animals remained in generally poor health for 4-5 days before recovering. All animals showed expected gains in bodyweight over the 14 -day study period. No abnormalities were noted at necropsy

 

Oral LD50 Combined > 5000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP). 

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:
5 000 mg/kg bw
Quality of whole database:
The key study is of good quality (Klimisch score = 2); a GLP study conducted equivalent to guideline methodologies.

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 February 12 to 26, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Although conducted under worst-case conditions (abraded skin, occlusive dressing), no mortality was observed during this study. A repeat study is unlikely to show worse effects; therefore, this study was considered sufficiently robust to cover this endpoint.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
other: Section 1500.4 - Federal Hazardous Substance Act Regulation - 16 CFR
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(abraded skin, occlusive dressing and 3 animals/sex used; no details on test animals and environmental conditions)
Principles of method if other than guideline:
The abraded skin of albino rabbits (3/sex) was occlusively exposed to undiluted test material for 24 hours at dose of 2000 mg/kg bw. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg

IN-LIFE DATES: From: February 12, 1981 To: February 26, 1981.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE: Abraded skin
- Area of exposure: Back
- % coverage: No data
- Type of wrap if used: Treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any excess material was removed.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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:
Animals were observed for mortality and clinical signs daily for 14 days. Initial and final bodyweights of animals were recorded.
- Necropsy of survivors performed: Yes; gross necropsies were performed on all animals which died during the 14-day observation period and also on all survivors of the 14 days observation period.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
- No mortality was observed
Clinical signs:
- No clinical signs were observed.
Body weight:
- Body weight changes were normal.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50 Combined > 2000 mg/kg bw
Executive summary:

In an acute dermal toxicity study (limit test) performed similarly to the OECD guideline No. 402 and in compliance with GLP, the abraded skin of albino rabbits (3/sex) was occlusively exposed to undiluted test material for 24 h at dose of 2000 mg/kg bw. Animals were observed for mortality, clinical signs and body weight changes daily for 14 days and then necropsied for macroscopic observations.

No mortality or clinical signs were observed. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

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 of good quality (Klimisch score = 2); a GLP study conducted equivalent to guideline methodologies. The study was conducted under worst-case conditions (abraded skin, occlusive dressing) and no mortality was observed during this study. A new study is unlikely to show worse effects; therefore, this study was considered sufficiently robust to cover this endpoint.

Additional information

Acute toxicity via oral route:

A key study was identified (Biosearch Inc., 1981). In this limit acute oral toxicity study performed similarly to the OECD test guideline No. 401, rats (5/sex) were administered a single oral dose of undiluted test material at 5000 mg/kg bw by gavage. 

2/5 males and 1/5 females were died within 24 h of dosing. Animals were depressed, ruffled, dirty within 3 -4 h of dosing and severely depressed or semicomatose after 5-6 h of dosing. Surviving animals remained in generally poor health for 4-5 days before recovering. All animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy

Oral LD50Combined > 5000 mg/kg bw.

Acute toxicity via dermal route:

A key study was identified (Biosearch Inc., 1981). In this limit acute dermal toxicity study performed similarly to the OECD test guideline No. 402 and in compliance with GLP, the abraded skin of albino rabbits (3/sex) was occlusively exposed to undiluted test material for 24 h at dose of 2000 mg/kg bw. Animals were observed for mortality, clinical signs and body weight changes daily for 14 days and then necropsied for macroscopic observations.

No mortality or clinical signs were observed. No abnormalities were noted at necropsy.

Dermal LD50 Combined > 2000 mg/kg bw


Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
Not required for substances at the REACH Annex VII tonnage level.

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Harmonized classification:

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

Self-classification:

Acute toxicity (Oral):

Based on the available information, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 5000 mg/kg bw.

Acute toxicity (Dermal):

Based on the available information, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the dermal LD50 is higher than 2000 mg/kg bw.

Acute toxicity (Inhalation):

No information was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 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 required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 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 Annex VI of the Regulation (EC) No 1272/2008 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.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No information was available.