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Administrative data

Description of key information

One GLP OECD study available for oral toxicity, 3 other values for oral. inhalation and dermal toxicity found in publicly available material (published sds), but with no further information on test methods etc.

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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
other: Crl: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories,Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 163 - 209 g
- Fasting period before study: 16 hours
- Housing: kept individually in MAKROLON cages (type III plus)
- Diet (e.g. ad libitum): Commercial ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany; served as food ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark
Route of administration:
oral: gavage
Vehicle:
other: Sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 18-207 mg/ml
- Amount of vehicle (if gavage): 1,7-2,1 ml
- Lot/batch no. (if required): Batch no. 5135601; Henry Lamotte Oils GmbH, 28197 Bremen, Germany

MAXIMUM DOSE VOLUME APPLIED: 2,1 ml:
Doses:
181 mg/kg b.w.
568 mg/kg b.w.
1809 mg/kg b.w.
2067 mg/kg b.w.
No. of animals per sex per dose:
181 mg/kg b.w. : 5
568 mg/kg b.w. : 5
1809 mg/kg b.w. : 1
2067 mg/kg b.w. : 1
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration, thereafter daily. Weighing: recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death . Changes in weight were calculated if survival exceeds one day.
- Necropsy of survivors performed: yes
- Other examinations performed: cDuring the follow-up period (two weeks), changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
The LD50 value and the confidence interval were calculated using the software “AOT425statpgm (Version: 1.0) . Acute Oral Toxicity (OECD Test Guideline 425) Statistical Programme (AOT 425 StatPgm). Version: 1.0, 2001. [http://www.oecd.org/chemicalsafety/¬testingofchemicals/¬section4software.htm]
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
568 mg/kg bw
Based on:
act. ingr.
95% CL:
> 256 - < 568
Key result
Sex:
female
Dose descriptor:
other: No-observed-effect level
Effect level:
< 181 mg/kg bw
Based on:
act. ingr.
Mortality:
181 mg/kg b.w. : None of 5 animals died during the 14 days obserservation period after administration
568 mg/kg b.w. 4 of 5 animals died within 24 hours after administration, 1 animal survived during the 14 days obserservation period after administration
1809 mg/kg b.w. 1 of 1 animal died within 24 hours after administration.
2067 mg/kg b.w. 1 of 1 animal died within 24 hours after administration.

Clinical signs:
181 mg/kg b.w.: reduced motility, ataxia, reduced muscle tone and dyspnoea in all 5 of 5 animals on test day one. No animal died prematurely.
568 mg/kg b.w. : reduced motility, ataxia, reduced muscle tone and dyspnoea in all 5 of 5 animals. Four of 5 animals died prematurely within 24 hours after administration.
1809 mg/kg b.w. : reduced motility, ataxia, reduced muscle tone, dyspnoea and dorsal position in the one animal employed. The animal died within 24 hours after administration.
2067 mg/kg b.w. : reduced motility, tremor, reduced muscle tone, dyspnoea and necrosis in the one animal employed. The animal died within 24 hours after administration.
Body weight:
163 - 209 g
Gross pathology:
No signs or abnormalities were observed at necropsy. All surviving animals gained the expected body weight.
Other findings:
None
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 of test item : 568 mg/kg b.w., by oral administration
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
568 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other: Material Safety data sheet
Species:
rat
Route of administration:
inhalation
Duration of exposure:
4 h
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
4-hour inhalation (Rat) LC50: 20 mg/l
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
20 000 mg/m³
Quality of whole database:
Unknown, data from published sds

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other: Material safety data sheet
Species:
rabbit
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute dermal toxicity (Rabbit) LD50: >2000 mg/kg
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Unknown, data from published sds

Additional information

Since the most reliable available data shows the most critical endpoint value and no further information, besides the value itself, on the 3 other endpoints studies are avilable, the performed OECD GLP is chosen as the definitive for the toxicity of the chemical.


Justification for selection of acute toxicity – oral endpoint
Most reliable endpoint study selected, GLP study done according to OECD guideline.

Justification for selection of acute toxicity – inhalation endpoint
Only data value available, reliability is unknown

Justification for selection of acute toxicity – dermal endpoint
Only data value available, reliability is unknown

Justification for classification or non-classification

Since the GLP OECD oral toxicity study performed showed a LD50 of 568 mg/kg b.w. and this falls within the classification criteria for classification as Acute oral toxicity category 4, according to CLP EU Regulation 1278/2008, we chose to classify as such.