Registration Dossier

Administrative data

Description of key information

Acute oral toxicity studies were conducted on four MDI category members; the substances EC number 406-530-2, 406-370-3, 445-760-8 and 406-690-3. The results from these studies showed no evidence of acute toxicity up to the highest dose tested in any study (2000 mg/kg test item in either cellulose or corn oil). There is no evidence of a relevant intrinsic acute oral toxicity requiring classification or substance specific risk management measures.

Acute dermal toxicity limit studies were conducted on four MDI category members; the substances EC number 406-530-2, 406-370-3, 445-760-8 and 406-690-3. The results from these studies showed no evidence of acute toxicity at the only dose tested in any study (2000 mg/kg test item). There is no evidence of a relevant intrinsic acute dermal toxicity requiring classification or substance specific risk management measures.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
10 male and 10 female rats
Route of administration:
oral: unspecified
Vehicle:
corn oil
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
10 animals per sex per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 2000 mg/kg bw ; Number of animals: 10; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 10; Number of deaths: 0
Clinical signs:
No deaths and no signs of toxicity were observed.
Gross pathology:
No effects on organs
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the test item was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no signs of toxicity were observed.
Executive summary:

The acute oral toxicity of the test item to Crj(CD)SD rats was determined in a limit test conducted according to international guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no signs of toxicity were observed.

The study is a GLP compliant, guideline study and is acceptable with restrictions.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Albino
Sex:
male/female
Details on test animals and environmental conditions:
5 male and 5 female rats
Route of administration:
oral: unspecified
Vehicle:
corn oil
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw ; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 5; Number of deaths: 0
Clinical signs:
No deaths and no signs of toxicity were observed.
Gross pathology:
No treatment-related macroscopic findings were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the test item to albino Wistar rats was determined to be > 2000 mg/kg b.w., the only concentration tested. No signs of toxicity were observed, and the gross pathological examination revealed no treatment-related findings.
Executive summary:

The acute oral toxicity of the test item to albino Wistar rats was determined in a limit test conducted according to international guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No signs of toxicity were observed, and the gross pathological examination revealed no treatment-related findings.

The study is a GLP compliant, guideline study and is acceptable with restrictions.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
corn oil
Remarks:
at 0.5 %
Doses:
5000 mg/kg b.w.
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Details on study design:
The total dose of 5000 mg/kg was given as two doses of 2500 mg/kg administered within a 24 hour period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: No clear toxicologically significant effects were seen.
Gross pathology:
Effects on organs: None.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the test item was determined to be > 5000 mg/kg b.w. No signs of toxicity were observed, and the gross pathological examination revealed no effects on organs.
Executive summary:

The acute oral toxicity of the test item to male and female Wistar rats was determined in a study conducted according to EU Annex V guidelines. The test item was administered to 5 male and 5 female rats, with the 5000 mg/kg/b.w. dose administered as two doses of 2500 mg/kg/b.w. in a 24 hour period. The LD50 was determined to be > 5000 mg/kg b.w. No signs of toxicity were observed, and the gross pathological examination revealed no effects on organs.

The study is a GLP compliant, guideline experimental study and is acceptable with restrictions.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
6 male and 3 female rats
Route of administration:
oral: unspecified
Vehicle:
methylcellulose
Remarks:
at 0.5 %
Doses:
200 and 2000 mg/kg b.w.
No. of animals per sex per dose:
3 animals per sex per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 200 mg/kg bw ; Number of animals: 3; Number of deaths: 0
Male: 2000 mg/kg bw ; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw ; Number of animals: 3; Number of deaths: 0
Clinical signs:
At doses of 200 and 2000 mg / kg, no clinical signs and no mortality were observed in the animals.
Body weight:
The overall weight change of the animals is not affected by the treatment with the substance.
Gross pathology:
No apparent abnormality is observed on macroscopic examination of the main organs of animals sacrificed at the end of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the test item was determined to be > 2000 mg/kg b.w. No signs of toxicity were observed, no effects on body weight were observed and the gross pathological examination revealed no treatment-related findings.
Executive summary:

The acute oral toxicity of the test item to Sprague-Dawley rats was determined in a study conducted according to OECD 423 and EU method B.1 guidelines. The LD50 was determined to be > 2000 mg/kg b.w. No signs of toxicity or effects on body weight were observed, and the gross pathological examination revealed no treatment-related findings.

 

The study is a GLP compliant, guideline experimental study and is acceptable with restrictions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
All studies evaluated for the MDI category have been conducted following standard guidelines and have been previously submitted for regulatory purposes; and therefore they are deemed acceptable for evaluation.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
corn oil
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
No deaths or signs of toxicity were observed.
Gross pathology:
No treatment-related effects on organs were observed
Other findings:
Signs of toxicity (local): At the site of treatment, spots with crusts were noted in 2 females on day 8 and 1 female on day 15
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the acute dermal exposure of rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
Executive summary:

The acute dermal toxicity of the test item was determined in a guideline limit test with male and female wistar rats at a dose level of 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths or effects on organs were observed. At the site of treatment, spots with crusts were noted in 2 females on day 8 and 1 female on day 15. The test item does not meet the GHS criteria and is not classified.

The study is a GLP compliant, guideline study suitable for use for assessment of this endpoint, with restrictions.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
corn oil
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
No deaths or signs of toxicity were observed.
Slight erythema was observed at the site of application in one female on day 2.
Gross pathology:
No treatment-related macroscopic findings were observed
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the acute dermal exposure of Wistar rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
Executive summary:

The acute dermal toxicity of the test item was determined in a guideline limit test with male and female Wistar rats at a dose level of 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths, gross pathological findings or signs of toxicity were observed, except slight erythema at the site of application in one female on day 2. Therefore, the test item does not meet the GHS criteria and is not classified.

The study is a GLP compliant, guideline study suitable for use for assessment of this endpoint with restrictions.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
Version / remarks:
Version not reported
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
corn oil
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Lethargy was noted in 1 male and 1 female during the treatment period.
Gross pathology:
No treatment-related effects on organs were observed.
Other findings:
Signs of toxicity (local): Slight erythema of treated skin was noted in one male on days 5 and 8 and scaliness in 1 male on day 5.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the acute dermal exposure of rats to the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
Executive summary:

The acute dermal toxicity of the test item was determined in a limit test conducted at a dose of 2000 mg/kg b.w., with male and female Wistar rats, according to EU Annex V guidelines. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested.

No deaths and effects on organs were observed. Lethargy was noted in 1 male and 1 female during the treatment period. Slight erythema of treated skin was noted in one male on days 5 and 8 and scaliness in 1 male on day 5. The test item does not meet the GHS criteria and is not classified.

The study is a GLP compliant, guideline experimental study and is suitable for use for assessment of this endpoint with restrictions.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
The substance was moistened with reverse osmosis purified water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
not specified
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
No clinical signs were observed.
Body weight:
A slower body weight gain or a slight decrease in body weight is noted in 2/5 females between days 1 and 8 and in 1/5 females between days 8 and 15. The body weight gain of other animals is similar to that of historical control animals.
Gross pathology:
No treatment-related effects on organs were observed
Other findings:
Signs of toxicity (local): No skin reaction is observed. A white coloring of the skin, due to the substance, could mask a very slight erythema and is noted in all the animals at day 2 only.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for the acute dermal exposure of the test item was determined to be > 2000 mg/kg b.w., the only concentration tested.
Executive summary:

The acute dermal toxicity of the test item was determined in a guideline limit test with male and female Sprague-Dawley rats at 2000 mg/kg b.w. The LD50 was determined to be > 2000 mg/kg b.w., the only concentration tested. No deaths and no effects on organs were observed. A slower body weight gain or a slight decrease in body weight is noted in 2/5 females between days 1 and 8 and in 1/5 females between days 8 and 15. The body weight gain of other animals is similar to that of historical control animals. No local skin reaction was observed, however a white colouring of the skin, due to the substance, could mask a very slight erythema is noted in all the animals at day 2 only. The test item does not meet the GHS criteria and is not classified.

The study is a GLP compliant, guideline experimental study and is suitable for use for assessment of this endpoint with restrictions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
All studies evaluated for the MDI category have been conducted following standard guidelines and have been previously submitted for regulatory purposes; and therefore they are deemed acceptable for evaluation.

Additional information

Justification for classification or non-classification

The oral and dermal LD50 values are greater than 2000 mg/kg bw in all studies conducted on the MDI category, therefore, existing data supports justification for non-classification.