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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 to 18 October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The acute oral toxicity study was undertaken as a bridging study to demonstrate equivalence between the Target substance (XP 475) and the Source substance (XP 338; CAS 569318-35-0) for the read-across of other data. A full discussion of read-across and supporting data is given in the attached justification.
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
27 November 2003 to 16 December 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 Dec 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
The substance is the Source of the read-across for other toxicological endpoints. The acute oral toxicity study shows equivalent results to the Target Substance.
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: gavage
Vehicle:
arachis oil
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 > 2500 mg/kg.
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
GLP compliance:
not specified
Specific details on test material used for the study:
Test material is a hydrolysis product of the test material XP 475.
Species:
rat
Route of administration:
oral: gavage
Sex:
not specified
Dose descriptor:
LD50
Effect level:
4 710 - 5 840
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
Isopropanol LD50 range = 4710 - 5840 mg/kg. Isopropanol is a hydrolysis product of the test material XP 475. The data is provided as supporting material for the assessment of XP 475.
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Specific details on test material used for the study:
Test material is a hydrolysis product of XP 475.
Species:
rat
Route of administration:
oral: gavage
Dose descriptor:
LD50
Effect level:
> 3 980 mg/kg bw
Based on:
test mat.
Mortality:
In rats, oral LD50 values of 3,980 mg/kg bw and higher (12,300 mg/kg bw
for males and 10,800 mg/kg bw for females) are reported. In a test with 5 male and 5 female rats
per dose, rats dosed 2-4 g/kg bw exhibited moderate diarrhea, rats dosed 8 g/kg bw showed
moderate to severe diarrhea. Doses of 10 g/kg bw killed 1/5 male and 2/5 female rats (clinical
signs: rapid erratic respiration, lethargy, severe diarrhea, ruffled and unkempt coats). After
forced feeding of 16 g/kg bw all rats died within 30 min.
Interpretation of results:
GHS criteria not met
Conclusions:
Ethyl acetoacetate, a hydrolysis product of XP 475, does not meet the criteria for classification.
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Specific details on test material used for the study:
Test substance is a hydrolysis product of target substance.
Species:
rat
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
Aluminium hydroxide: LD50 (rat) > 5000 mg/kg.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
17th December 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Female, nulliparous and non pregnant animals.
Age of animals: Young adult rat, 8-9 weeks old in sighting and in main study.
Body weight in sighting study: 191 g.
Body weight range in main study: 193 - 214 g.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other:
Remarks:
The test item was dosed as a formulation in Helianthi annui oleum raffinatum solution.
Details on oral exposure:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage.
Doses:
Starting dose of the sighting study was selected on the OECD Guideline No.:420. A sighting study starting dose of 2000 mg/kg followed by dosing of a further four animals at this level as a limit test for relevant guideline.
No. of animals per sex per dose:
Starting dose of the sighting study was selected on the OECD Guideline No.:420. A sighting study starting dose of 2000 mg/kg followed by dosing of a further four animals at this level as a limit test for relevant guideline.
Control animals:
yes
Details on study design:
Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 14th day after the treatment.

Results and discussion

Preliminary study:
No lethality was noted at after a single oral dose of 2000 mg/kg bw.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The rat (No.: 7548) dosed at 2000 mg/kg bw XP 475 did not die in sighting study.
No deaths occurred at the 2000 mg/kg single oral dose of the test item in the main study. All rats survived until the end of the 14-day observation period.
Clinical signs:
No treatment related symptoms were observed in the 2000 mg/kg bw dose group throughout the 14-day post-treatment period.
Body weight:
The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2000 mg/kg bw of the test item survived until the scheduled necropsy on Day 14.
Slight hydrometra was observed in female No.: 7548 and severe hydrometra was detected in animal No.: 7551, respectively. Hydrometra is physiological finding and connected to the oestrus cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw of the test item.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 >2000 mg/kg.