Registration Dossier

Administrative data

Description of key information

The oral LD50 of the test item in female rats has been determined to be greater than 2000 mg/kg bw. 
The dermal LD50 in rats was determined to be > 2000 mg/kg bw.

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:
12 November 2013 to 05 December 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD test guideline method.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: RccHan : WIST(SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. Horst, The Netherlands
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 193.4 to 213.7g
- Fasting period before study: Overnight
- Housing: Makrolon Type 4 cages
- Diet (e.g. ad libitum): Teklad Rat-Mouse diet 2914C ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 6 to 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): >30%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From: 12 November 2013 To: 05 December 2013
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The LD50in rats is
>5000 mg/kg body weight (based on data from components or similar materials), therefore the
starting dose was set at 2000 mg/kg body weight.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily during acclimatization; prior to treatment, within the first 30 minutes and approximately 1, 2, 3
and 5 hours after treatment on test day 1; once daily during test days 2 - 15. Body weights were taken at start of acclimatization, on test day 1 (prior to treatment), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.
Preliminary study:
A preliminary study was performed in a single animal at 2000 mg/kg body weight.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occured during the course of the study.
Clinical signs:
After treatment on test day 1, 2 of 5 animals (animal nos. 2 and 3) showed ruffled fur at all observation time points (within 0.5 h and at 1, 2, 3 and 5 hours). From test day 2 onwards, no clinical signs were observed in any animal.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings wererecorded at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days, is: LD50(female rat): greater than 2000 mg/kg body weight.
Executive summary:

Test Guidance

The acute toxicity of the test substance when administered by a single oral gavage to rats was investigated according to OECD test guideline No. 420 and Commission Regulation (EC) No. 440/2008, B.1.

Method

To determine the dose level for the main study, one sighting study was conducted with one female RccHan:WIST (SPF) rat. The animal was treated with the test item at a dose level of 2000 mg/kg body weight by single oral gavage administration. The test item was formulated in Polyethylene glycol 300 (PEG 300) at a concentration of 0.2 g/mLand administered at a dosing volume of 10 mL/kg body weight. Since no mortality occurred in the animal dosed at 2000 mg/kg, four additional females were treated at this dose level in the main study. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 - 15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during testdays 2 - 15. Body weights were recorded at acclimatization start, on test day 1 (prior to administration), on test days 8 and 15. All animals were necropsied and macroscopically examined.

Results

No intercurrent deaths occurred during the course of the study. After treatment on test day 1, 2 of 5 animals showed ruffled fur at all observation time points. From test day 2 onwards, no clinical signs were observed in any animal. The body weight of the animals was within the range commonly recorded for this strain and age. No abnormal macroscopic findings were recorded at necropsy.

Conclusion

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days, is: LD50(female rat): greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Klimisch grade 1, modern GLP compliant study.

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:
12 November 2013 to 03 December 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in accordance with recognised guideline
Justification for type of information:
With regard to why some higher tier testing was conducted and included in this dossier without prior to submission of a testing proposal to EU:  global chemical companies who manufacture and/or place substances on the global market are obligated to meet the relevant chemical control laws in each jurisdiction that they do business. For this EC number 941-129-0, additional testing was required in order to meet global registration requirements outside of the EU.  The requirements of Article 22 of REACH place a responsibility on the registrant to update their registration with relevant new information.  These additional studies required for non-EU global registration purposes were deemed as relevant information and hence they were included in the EU REACH dossier. 
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: RccHan WIST(SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, B.V. Horst, Netherlands
- Age at study initiation: 8 to 12 Weeks
- Weight at study initiation: Males 242.6 to 281.7g, Females 208.79 to 210.74g
- Fasting period before study: None
- Housing: Makrolon Type 3 cages furnished with woodflakes.
- Diet (e.g. ad libitum): Teklad Rat-Mouse Rodent Diet. ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 °C
- Humidity (%): >30 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light/dark cycle


IN-LIFE DATES: 12 November 2013 to 03 December 2013
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: ca. 10%
- Type of wrap if used: self adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm water, dried with paper towels.
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 500 mg/ml, 4 ml/kg body weight
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
Single dose level of 2000 mg/kg bodywight
No. of animals per sex per dose:
5m, 5f, dosed at 2000 mg/kg bw
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity ½, 1, 2, 3 and 5 hours after dosing and subsequently twice daily for 15 days. Animals were weighed on days 1, 8 and 15
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, dermal reaction
Statistics:
No statistical analysis was performed.
Preliminary study:
not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occured during the course of the study.
Clinical signs:
Scratching was observed on the back of one female (animal No. 7) during the first two days after removal of dressing.
Body weight:
The body weight of animals was within the range commonly recorded for this strain and age.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of the test substance after single dermal application to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight.
Executive summary:

Test Guidance

OECD Guideline 404 and EC Method B3

Method and materials

Five male and five female RccHan:WIST (SPF) rats were treated with the test substance at the limit dose of 2000 mg/kg by dermal application. The test item was formulated in PEG 300 at a concentration of 0.5 g/mL and administered at a dose volume of 4 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability, clinical signs and local dermal signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutesand approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 - 15. Local dermal signs were noted once daily from test day 2 to 15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during test days 2 - 15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were necropsied and macroscopically examined.

Results

No intercurrent deaths occurred during the course of the study. Scratching was observed on the back of one female during the first two days after removal of dressing. No local dermal signs were observed throughout the entire observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Conclusion

The median lethal dose of the test substance after single dermal application to rats of both sexes, observed over a period of 14 days, is: LD50 (rat) greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Klimisch grade 1, modern GLP compliant study.

Additional information

Oral

The acute toxicity of the test item when administered by a single oral gavage to rats was investigated according to OECD test guideline No. 420 and Commission Regulation (EC) No. 440/2008, B.1. To determine the dose level for the main study, one sighting study was conducted with one female RccHan:WIST (SPF) rat. The animal was treated with the test item at a dose level of 2000 mg/kg body weight by single oralgavage administration. The test item was formulated in Polyethylene glycol 300 (PEG 300) at a concentration of 0.2 g/mLand administered at a dosing volume of 10 mL/kg body weight. Since no mortality occurred in the animal dosed at 2000 mg/kg, four additional females were treated at this dose level in the main study. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 - 15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during testdays 2 - 15. Body weights were recorded at acclimatization start, on test day 1 (prior to administration), on test days 8 and 15. All animals were necropsied and macroscopically examined.

No intercurrent deaths occurred during the course of the study. After treatment on test day 1, 2 of 5 animals showed ruffled fur at all observation time points. From test day 2 onwards, no clinical signs were observed in any animal. The body weight of the animals was within the range commonly recorded for this strain and age. No abnormal macroscopic findings were recorded at necropsy.

The median lethal dose of the test item after single oral administration to female rats, observed over a period of 14 days, is: LD50(female rat): greater than 2000 mg/kg body weight.

Dermal

In accordance with OECD Guideline 404 and EC Method B3, five male and five female RccHan:WIST (SPF) rats were treated with test item at the limit dose of 2000 mg/kg by dermal application. The test item was formulated in PEG 300 at a concentration of 0.5 g/mL and administered at a dose volume of 4 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability, clinical signs and local dermal signs were recorded. All animals were examined for clinical signs before treatment, within the first 30 minutesand approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2 - 15. Local dermal signs were noted once daily from test day 2 to 15. Mortality/viability was recorded before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during test days 2 - 15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were necropsied and macroscopically examined.

No intercurrent deaths occurred during the course of the study. Scratching was observed on the back of one female during the first two days after removal of dressing. No local dermal signs were observed throughout the entire observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose of the test item after single dermal application to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg body weight.

Inhalation

The substance is a liquid with a vapour pressure of 0.000028 Pa at 25°C and is used primarily as a component of lubricants and greases by workers and consumers. It is expected that inhalation exposure from these uses will be low and that the most likely route of exposure for workers and consumers is the dermal route.


Justification for selection of acute toxicity – oral endpoint
One study is available. Guideline, GLP study; K=1

Justification for selection of acute toxicity – dermal endpoint
One study is available. Guideline, GLP study; K=1

Justification for classification or non-classification

In an acute oral toxicity study in rats the LD50 was determined to be > 2000 mg/kg bw.

In an acute dermal study in rats the LD50 was determined to be > 2000 mg/kg bw.

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for acute toxicity