Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral in rats: LD50 > 2000 mg/kg bw (OECD 420, GLP, K, Rel. 1)

In an acute dermal toxicity study, the dermal LD50 of was estimated higher than 5000 mg/kg bw in rats (Rel. K2).

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:
March 03 to 26, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 420 without any deviation.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on March 12 to 14, 2014/ signed on May 12, 2014)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 159-176 g
- Fasting period before study: Animals were fasted for overnight period before dosing and for approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes / h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: March 03 to 26, 2015
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: DMSO was used as vehicle because the test item did not dissolve/suspend in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: For the purpose of the study, the test item was freshly prepared, as required, as a suspension in dimethyl sulphoxide. The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
Doses:
- Sighting study: 300 and 2000 mg/kg bw
- Main study: 2000 mg/kg bw
No. of animals per sex per dose:
- Sighting study: 1 female/dose
- Main study: 5 females/dose (1 animal included from sighting study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 h after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the observation period, animals were killed by cervical dislocation and subjected to gross necropsy.
Statistics:
None
Preliminary study:
- No mortality or clinical signs were observed at 300 mg/kg bw.
- The animal showed expected gains in body weight over the observation period.
- No abnormalities were noted at necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 2000 mg/kg bw.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Rat Oral LD50 (females) > 2000 mg/kg bw
Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, groups (5 females/dose) of Wistar (RccHan™:WIST) rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Sighting study was conducted at the dose levels of 300 and 2000 mg/kg bw (one female/dose) to determine the dose for main study.

 

In the sighting study, no mortality or clinical signs were observed at 300 mg/kg bw. The animal showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy. In the main study, no mortality or clinical signs were observed at 2000 mg/kg bw. All animals showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Rat Oral LD50 (females) > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Adequate for hazard assessment

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Basic data given, but considered sufficiently reliable for the purpose of hazard assessment
Reason / purpose:
read-across: supporting information
Principles of method if other than guideline:
Standard acute method (limit test)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No data
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
5 000 mg/kg bw
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
No data
Preliminary study:
No data
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
The test material adhered tightly to the skin and could not be removed with standard washing procedures. the skin surface was therefore obscured and initial erythema would have escaped detection.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.
Executive summary:

In an acute dermal toxicity study (limit test), rabbits were given a single dermal application of the test item at 5000 mg/kg bw. Animals were observed for mortality and clinical signs for 14 days.

No mortality or clinical signs was observed.

In this study, the dermal LD50 of the test item was higher than 5000 mg/kg bw in rats.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Cystus concrete and Cyste absolute are obtained from the same botanical source, the Cistus ladaniferus (Cistaceae).
Reason / purpose:
read-across source
Principles of method if other than guideline:
Standard acute method (limit test)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No data
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
5 000 mg/kg bw
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
No data
Preliminary study:
No data
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
The test material adhered tightly to the skin and could not be removed with standard washing procedures. the skin surface was therefore obscured and initial erythema would have escaped detection.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test substance is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS. Therefore, the registered substance is not considered toxic by dermal route.
Executive summary:

In an acute dermal toxicity study (limit test), rabbits were given a single dermal application of the test item at 5000 mg/kg bw. Animals were observed for mortality and clinical signs for 14 days.

No mortality or clinical signs was observed.

In this study, the dermal LD50 of the test item was higher than 5000 mg/kg bw in rats.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS. Therefore, the registered substance is not considered toxic by dermal route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, groups (5 females/dose) of Wistar (RccHan™:WIST) rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Sighting study was conducted at the dose levels of 300 and 2000 mg/kg bw (one female/dose) to determine the dose for main study.

 

In the sighting study, no mortality or clinical signs were observed at 300 mg/kg bw. The animal showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy. In the main study, no mortality or clinical signs were observed at 2000 mg/kg bw. All animals showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Rat Oral LD50 (females) > 2000 mg/kg bw

Acute dermal toxicity:

In an acute dermal toxicity study (limit test), rabbits were given a single dermal application of the cyste absolute at 5000 mg/kg bw. Animals were observed for mortality and clinical signs for 14 days.

No mortality or clinical signs was observed.

In this study, the dermal LD50 of the test item was higher than 5000 mg/kg bw in rats.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.Therefore, the registered substance is not considered toxic by dermal route.

 

Justification for classification or non-classification

Self classification:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the oral and dermal LD50 are higher than 5000 mg/kg bw.