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Administrative data

Description of key information

In an acute oral and a dermal toxicity study with rats, performed according to OECD/EC test guidelines and GLP principles, oral and dermal LD50 values of >2000 mg/kg bw  for Y-513 were determined.

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:
19 February - 06 March 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD and EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 148-165g
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): Free access to pelleted rodent diet
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 - 21.6
- Humidity (%): 39 - 67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.


DOSAGE PREPARATION:
The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines.
Doses:
First set of females 2000 mg/kg
Second set of females 2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Mortality/Viability: Twice daily for 15 days.
- Body weights: Days 1 (pre-administration), 8 and 15.
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes.
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, uncoordinated movements and/or piloerection were noted in all animals on Day 1. In addition, yellow faeces were noted in all animals on Days 2 or 3.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines and GLP principles, an LD50 >2000 mg/kg bw for Y-513 was determined.
Executive summary:

An acute oral toxicity study was performed with rats according to OECD/EC test guidelines and GLP principles following the acute toxic class method. Two groups of three female rats were exposed to 2000 mg/kg bw, no mortality occurred. Hunched posture, uncoordinated movements and/or piloerection were noted in all animals on day 1. No changes in expected body weight gain occurred, no abnormalities were found at necropsy.

Based on these data, the LD50 for Y-513 was determined exceed 2000 mg/kg bw, the substance is thus not classified for oral toxicity according to Regulation (EC) 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study was performed according to OECD and EC guidelines and according to GLP principles (klimisch 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
18 June - 02 July 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD and EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: males around 247-262 g, females around 167-177 g
- Fasting period before study: not applicable
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): Free access to pelleted rodent diet
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 – 21.7
- Humidity (%): 41 - 73
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm2 for males and 18 cm2 for females
- % coverage: test site covered for 100%
- Type of wrap if used: The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin cleaned of residual test substance using tap water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 mL/kg) body weight.

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 ml/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Mortality/Viability: Twice daily for 15 days.
- Body weights: Days 1 (pre-administration), 8 and 15.
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted in two animals on Day 1. This symptom is more often seen in these types of studies. Based on the mild nature and short duration of this symptom and the absence of any corroborative signs in these animals, it was considered to be of no toxicological significance.

Scales and/or scabs on the treated skin were observed in the majority of the animals during the observation period.

Yellow staining of the skin was noted during the observation period which was considered to be related to the staining properties of the test substance.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No toxicologically relevant abnormalities were found at macroscopic post mortem examination of the animals.

Incidental findings:
In one male, reduced size of the left testis and epididymis was found, which is occasionally noted among rats of this age and strain and was therefore considered not toxicologically significant.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines and GLP principles, an LD50 >2000 mg/kg bw for Y-513 was determined.
Executive summary:

An acute dermal toxicity study was performed with rats according to OECD/EC test guidelines and GLP principles. Rats (5/sex) were exposed to 2000 mg/kg bw for 24 hours. No clinical signs were noted, no mortality occurred. No changes in expected body weight gain occurred, no abnormalities were found at necropsy.

Based on these data, the dermal LD50 for Y-513 was determined exceed 2000 mg/kg bw, the substance is thus not classified for dermal toxicity according to Regulation (EC) 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study was performed according to OECD and EC guidelines and according to GLP principles (klimisch 1).

Additional information

An acute oral toxicity study was performed with rats according to OECD/EC test guidelines and GLP principles following the acute toxic class method. Two groups of three female rats were exposed to 2000 mg/kg bw, no mortality occurred. Hunched posture, uncoordinated movements and/or piloerection were noted in all animals on day 1. No changes in expected body weight gain occurred, no abnormalities were found at necropsy. Based on these data, the oral LD50 for Y-513 was determined to exceed 2000 mg/kg bw.

An acute dermal toxicity study was performed with rats according to OECD/EC test guidelines and GLP principles. Rats (5/sex) were exposed to 2000 mg/kg bw for 24 hours. No clinical signs were noted, no mortality occurred. No changes in expected body weight gain occurred, no abnormalities were found at necropsy. Based on these data, the dermal LD50 for Y-513 was determined to exceed 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
One reliable study available.

Justification for selection of acute toxicity – dermal endpoint
One reliable study available.

Justification for classification or non-classification

Based on the available data the substance is not classified for acute oral and dermal toxicity according to Regulation (EC) 1272/2008.