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Administrative data

Description of key information

ORAL
LD50 = 1054.03 mg/kg bw (male rat); sound scientific principles; Smyth, 1969
INHALATION
LC50 = > 6.6 mg/l (4h) rat; weight of evidence basis
DERMAL
LD50 = 609.21mg/kg bw (rabbit); sound scientific principles; Smyth, 1969

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:
Not reported.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 rats were administered a single oral dose of test material, by gavage, and observed for 14 days following treatment.
GLP compliance:
not specified
Test type:
other: Not reported.
Limit test:
no
Species:
rat
Strain:
other: Carworth-Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 90 - 120 g
- Fasting period before study: None
- Diet (e.g. ad libitum): Rockland rat diet
Route of administration:
oral: gavage
Vehicle:
other: Unchanged when possible, otherwise diluted in water or corn oil.
Doses:
Arranged in a logarithmic series differing by a factor of 2.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
14 day observation period.
Statistics:
An approximate LD50 value was calculated according to the method detailed in Thompson (1947) using the table of Weil (1952). With a SD of ± 1.96.
Sex:
male
Dose descriptor:
LD50
Effect level:
1.09 mL/kg bw
Based on:
test mat.
95% CL:
0.66 - 1.8
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test material in rats was determined to be 1.09 mL/kg. Using the density of 0.967g/cm³ from Hawley et al (1977) this converts to an LD50 of approximately 1054.03 mg/kg.
Executive summary:

The acute oral toxicity of the test material was determined by administering rats with oral varying doses of test material and observing them for 14 days following treatment for any signs of toxicity. Under the conditions of the study, the oral LD₅₀ of the test material in rats was determined to be 1.09 ml/kg. Using the density of 0.967g/cm³ from Hawley et al (1977) this converts to an LD₅₀

of approximately 1054.03 mg/kg

According to Regulation 1272/2008 the test material requires classification under acute oral toxicity "category 4, H302: Harmful if swallowed".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 054.03 mg/kg bw
Quality of whole database:
The key study was assigned a reliability score of of 2. Two further studies and 3 Material Safety Data Sheets were assigned reliability scores of 4. Results reported accross all data sources were in good agreement and hence the quality of the overall dataset is considered to be good.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
not specified
Adequacy of study:
weight of evidence
Study period:
Not reported.
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Product information from a company SDS and accompanying specification.
Qualifier:
no guideline followed
Principles of method if other than guideline:
No information provided on materials and methods; information presented as short abstracts in the Material Safety Data Sheet.
GLP compliance:
not specified
Test type:
other: not reported
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
6 600 other: mg/m³
Based on:
test mat.
Exp. duration:
4 h
Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 was reported to be 6600 mg/m³ which converts to 6.6 mg/L. According to Regulation 1272/2008 the test material would be classified under acute inhalation toxicity as "category 3, H331: toxic if inhaled" (assuming the test material was dosed as a vapour).
Executive summary:

The LC50 was reported to be 6600 mg/m³ which is equivalent to 6.6 mg/L. According to Regulation 1272/2008 the test material would be classified under acute inhalation toxicity as "category 3, H331: toxic if inhaled" (assuming the test material was dosed as a vapour). The information was reported as a short abstract (in a company MSDS) and there is no available information on the methods adopted.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
6 600 mg/m³
Quality of whole database:
Six study summaries have been included to assess the acute inhalation toxicity of the test material. All studies were assigned relaibility scores of 4 as they lacked detail on experimental methods. The results reported were, in the main, in fairly good agreement with each other and hence the quality of the dataset overall is reasonable.

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:
Not reported.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Four male rabbits were administered test material, which was held in contact with skin for an exposure period of 24 hours. Following exposure, animals were observed for 14 days. Signs of toxicity and mortality were recorded and skin reactions were assessed according to the Draize scale (Draize (1944), one-day cuff).
GLP compliance:
not specified
Test type:
other: not reported.
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5 to 3.5 kg

No further information on test animals and environmental conditions is available.
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE:
Prepared by clipping the fur from the entire trunk.

No further information on dermal exposure is available.
Duration of exposure:
24 hours, during which animals were immobilized.
No. of animals per sex per dose:
4 per dose
Control animals:
not specified
Details on study design:
- observation period of 14 days post exposure.
Statistics:
An approximate LD50 value was calculated according to the method detailed in Thompson (1947) using the table of Weil (1952). With a SD of ± 1.96.
Sex:
male
Dose descriptor:
LD50
Effect level:
0.63 mL/kg bw
Based on:
test mat.
95% CL:
0.39 - 1.03

No further information on results is reported.

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of the test material was reported to be 0.63 mL/kg. Using the density stated in Hawley et al (1977), which is 0.967 g/cm³, the recorded LD50 converts to 609.21 mg/kg.
Executive summary:

The acute dermal toxicity of the test material was determined by exposing 4 male New Zealand white rabbits, per dose, to the test material. The test material was fixed occlusively to the trunk of the test animals for 24 hours. Mortalities were recorded over an observation period of 14 days post exposure. The acute dermal LD50 was determined to be 0.63 ml/kg. Using the density stated in Hawley et al (1977), the LD₅₀converts to 609.21 mg/kg. According to Regulation 1272/2008 the test material requires classification as "category 3, H311: Toxic in contact with skin".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
609.21 mg/kg bw
Quality of whole database:
The key study was assigned a reliability score of of 2. One further study and two Material Safety Data Sheets were assigned reliability scores of 4. Results reported accross all data sources were in good agreement and hence the quality of the overall dataset is considered to be good.

Additional information

ACUTE ORAL TOXICITY

The key study (Smyth, 1969) reported the LD₅₀ to be1054.03 mg/kg. Five male Carworth-Wistar rats were exposed per dose to varying concentrations of the test material, administered by oral gavage. Mortalities were recorded over a 14 day observation period and an LD₅₀ calculated. The study was performed to a good standard and was assigned a reliability score of 2 using the principles for assessing data quality as set out in Klimisch (1997).

Two studies and three material safety data sheets have been provided as supporting data. The two studies determined the oral toxicity by to be; Foulger (1948) minimum lethal dose to be 1000 mg/kg, and Pullin (1975) LD₅₀1000 mg/kg. The material safety data sheets recorded the oral toxicity as follows; Sigma Aldrich (2012) LD₅₀1058 mg/kg, and both TCI (2012) and Alfa Aesar record the LD₅₀as 1057.3 mg/kg. All five studies provided have been taken from abstracts, where only limited details regarding methodology are available. They have been assigned a reliability score of 4, according to the principles for assessing data reliability set out in Klimisch (1977). There is sufficient consistency between the sources to provide support to the key study and validate the classification.

 

ACUTE DERMAL TOXICITY

The key study (Smyth, 1969) determined the LD₅₀ to be 609.21 mg/kg. Four New Zealand white rabbits, per dose, were exposed to the test material. The test material was fixed occlusively to the trunk of the test animals for 24 hours. Mortality was recorded over an observation period of 14 days post exposure. The dermal toxicity was determined to be 0.63 ml/kg, using the density stated in Hawley at al (1977), the LD₅₀converts to 609.21 mg/kg. The study was performed to a good standard and was assigned a reliability score of 2 using the principles for assessing data quality as set out in Klimisch (1997).

Two safety data sheets have been provided as supporting data and have recorded the LD₅₀ as follows; Alfa Aesar (2007) 611.1 mg/kg and Sigma Aldrich (2012) 612 mg/kg. Test guidelines or methods are not mentioned in the abstracts and have thus been assigned a reliability score of 4, according to the principles for assessing data quality set out in Klimisch (1977). There is sufficient consistency between the sources to provide support to the key study and validate the classification.

 

Pullin (1975) determined the LD₅₀ to be > 1000mg/kg. The study has been provided as supporting data as it confirms that the test material causes systemic toxicity, however the derived value is not in agreement with the general consensus of data presented.

ACUTE INHALATION TOXICITY

One study (Smyth, 1969) and three safety data sheets have been provided to address the acute inhalation toxicity endpoint using the weight of evidence approach. Pullin (1975) and Foulger (1948) have been provided as supporting data.

Smyth (1969) determined the LC₅₀ to be > 2000 and < 4000 ppm. Six male rats per dose, were exposed to the test material as a metered vapour. Exposure occurred over a duration of 4 hours and the animals were observed and mortalities recorded over a 14 day period. The test material was reported to cause mortality at a rate of 1/6 at 2000 ppm and 6/6 at 4000 ppm therefore the LC₅₀ would be > 2000 and < 4000 ppm. Smyth (1969) has been assigned a reliability score of 2, in line with the principles for assessing data quality as set out in Klimisch (1977).

The safety data sheets recorded the inhalation toxicity as follows; TCI (2012) LCLo 2000 ppm, and both Sigma Aldrich (2012) and Alfa Aesar record the LC₅₀ as 6.6 mg/kg. Test guidelines or methods are not mentioned in the abstracts. The safety data sheets have been assigned a reliability score of 4, according to Klimisch (1977).

There is sufficient consistency between these sources to provide a weight of evidence and justify a classification. Due to the variation in the values for toxicity the LC₅₀ has been recorded on a worst case basis.

Pullin (1975) determined the LCby exposing rats to the test material at 42.94 mg/l for two hours. This value from this study has been disregarded based on the exposure duration. Foulger (1948) cannot be used to derive a classification based given the results. Both studies have been provided as supporting data, as they supports the conclusion that the test material is acutely toxic and causes respiratory irritation. They have been assigned a reliability score of 4, according to Klimisch (1977).


Justification for selection of acute toxicity – oral endpoint
The study was assigned a relaibility score of 2 according to the principles for assessing data quality as set out in Klimisch (1997) whereas all of the supporting studies were assigned reliability scores of 4.

Justification for selection of acute toxicity – inhalation endpoint
The studies were considered together in a weight of evidence approach. The lowest value recorded for LC50 of the test material is taken forward for risk assessment to consider the worst case scenario.

Justification for selection of acute toxicity – dermal endpoint
The study was assigned a relaibility score of 2 according to the principles for assessing data quality as set out in Klimisch (1997) whereas all of the supporting studies were assigned reliability scores of 4.

Justification for classification or non-classification

ACUTE ORAL TOXICITY

The oral toxicity studies and data from the material safety data sheets indicate that the test material requires classification. Under Regulation 1272/2008 the test material should be classed as "Category 4, H302: Harmful if swallowed”, and signal word “Warning”.

 

ACUTE DERMAL TOXICITY

The dermal toxicity studies and data from the material safety data sheets indicate that the test material requires classification. Under Regulation 1272/2008 the test material should be classed as "Category 3, H311: Toxic in contact with skin”, and signal word “Danger”.

 

ACUTE INHALATION TOXICITY

The inhalation toxicity studies and data from the material safety data sheets indicate that the test material requires classification. Under Regulation 1272/2008 the test material should be classed as "Category 3, H331: Toxic if inhaled”, and signal word “Danger”.