Registration Dossier

Administrative data

Description of key information

Oral: LD50> 2000 mg/kg bw, male and female rat, OECD 401, Anon, 1991.

Dermal: LD50> 2000 mg/kg bw, male and female rat, OECD 402, Anon, 1991.

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:
13 December 1990 to 27 December 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The methodology used in this study was equivalent to the current guideline requirements at the time the study was conducted. Although there are some minor deficiencies in reporting compared to modern requirements, the study is considered suitable as a key study for acute oral toxicity.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not applicable
Principles of method if other than guideline:
The procedures used in this study met the requirements of the test for acute oral toxicity described in document L251/1. an EEC Commission Directove of 25 April 1984.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4 ºC / Dark
- Stability under test conditions: Assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: N/A
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD(SD)BR Strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Source: Recognised supplier
-Age/weight at study initiation: 4-6 weeks / 100 grams
-Fasting period before study: over night fasting
-Housing: groups of five in grid bottom cages
-Diet: Pelleted rodent diet ad libitum
-Water: main drinking water via polypropylene bottles
-Acclimation period: 6 days

ENVIRONMENTAL CONDITION
-Temperature: 18 -21°C
-Humidity: 30 - 70%
-Air changes (per hour): Air conditioned
Photoperiod (hrs dark/hrs light: 12 hrs dark/12 hrs light
Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
test item suspended in corn oil giving dose of 10 ml/kg
Details on oral exposure:
The prepared test item was administered to one group of 10 rats (5/sex) at oral dose of 2000 mg/kg/bw. by peroral injection using a rubber catheter attached to a syringe.
Doses:
A single doise of 2000 mg/kg
No. of animals per sex per dose:
5 per sex per dose; 10 in total
Control animals:
no
Details on study design:
A single dose administration followed by 14 days observation periood.
Fregrancy of observation and weighing: the animals were examined at approximately 30 minutes and 1, 2 and 14 hours after dosing then once daily for 14 days. Animal weights were taken at a weekly intervals
Necropsy of surving animals: Yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female death reported on day two, no clinical signs were observed prior to its death.
Clinical signs:
Piloerection in one male after 2 - 4 hours of dosing which was noted in all surving animals. Hypoactivity in all males and two females.
Body weight:
all animals gained body weight.
Gross pathology:
Gastric non-glandular mucosa and salivary glands reddened in 4/5 males, left testis enlargemnet in one male and fluid distented uterus in 2/5 females, these were consitent with normal macroscopic background pathlogy.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the condition of this study the LD50 was dertermined to be > 2000 mg/kg/bw in male and female rats.
Executive summary:

A GLP study was performed folowing a method similar to OECD 401 to assess the toxicity of the test item following oral administration to Sprague-Dawley rats. The test item was administered as a single dose to a group 5 males and 5 female rats at dose level of 2000 mg/kg bw, this is followed by 14 days observation period for any signs of toxicity or any other effects of treatment. All animals were examined for gross patholog, one female death noted on day two of treatment. Piloerection and hyperactivity were noted in majority of the animals, one male exhibited a hunched posture - all clinical signs subsided by day 3. Necropsy findings were consitent with normal macroscopic background pathathology. Under the conditions of this study the LD50 was determined to be > 2000 mg/kg bw in male/female Sprague-Dawley rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
06 June 1991 to 20 June 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The methodology used in this study was equivalent to the current guideline requirements at the time the study was conducted. Although there are some minor deficiencies in reporting compared to modern requirements, the study is considered suitable as a key study for acute oral toxicity.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not applicable
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
not applicable
Principles of method if other than guideline:
The procedures used in this study met the requirements of the test for acute dermal toxicity described in document L251, an EEC Commission Directive of 25th April 1984.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4 ºC / Dark
- Stability under test conditions: Assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: N/A
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Source: Recognised supplier
-Age/weight at study initiation: young adult / 200 - 300 grams
-Fasting period before study: over night fasting
-Housing: groups of five in grid bottom cages
-Diet: Pelleted rodent diet
-Water: main drinking water via polypropylene bottles
-Acclimation period: 5 days

ENVIRONMENTAL CONDITION
-Temperature: 19 -22°C
-Humidity: 39 - 62%
Photoperiod (hrs dark/hrs light: 12 hrs dark/12 hrs light)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test site
- Area of exposure: clipped back with an Oster Model A5 clipper with size 40 blade.
- Type of occlusion if used: surgical gauze four pile thick overlaid with a strip of aluminium foil held in place with elastoplast of 5.0 cm wide.
Duration of exposure:
24 hours
Doses:
2000 mg/kg/bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 and subsequent daily for 14 consecutive days.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, including the nature, severity, approximate time of onset and duration of each sign. Individual body weight of rats on Days 1 (day of dosing), 8 and 15.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single dermal dose of the test item at 2000 mg/kg bodyweight.
Clinical signs:
There were no signs of systemic reaction. Incidence of enlarged submandibular lymp node was slighly higher but was consistent with normal background pathology.
Body weight:
All animals acheived anticipated body weight gains throughout the study.
Gross pathology:
No gross pathological findings were observed, autopsy revealed no macroscopic abnirmalities.
Interpretation of results:
GHS criteria not met
Conclusions:
The results of an acute dermal toxicity study on the test item didt not produce any signs of toxicity and the acute lethal dermal dose LD50 to rats was found to be > 2000 mg/kg bodyweight.
Executive summary:

An acute dermal toxicity study was performed using a method similar to OECD Guideline for Testing of Chemicals 402 "Acute Dermal Toxicity", and EEC Methods for the determination of toxcity, Directives 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B3. Acute Toxicity (Dermal). The application of of the test item at a single dose of 2000 mg/kg bw to the dorsal skin of 5 rats/sex under occlusive dressing for 24hours did not produce any signs of toxicity and it is concluded that the acute dermal dose LD50 to rats was found to be in excess of 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute Oral Toxicity (Anon, 1991): A GLP study was performed folowing a method similar to OECD 401 to assess the toxicity of the test item following oral administration to Sprague-Dawley rats. The test item was administered as a single dose to a group 5 males and 5 female rats at dose level of 2000 mg/kg bw, this is followed by 14 days observation period for any signs of toxicity or any other effects of treatment. All animals were examined for gross patholog, one female death noted on day two of treatment. Piloerection and hyperactivity were noted in majority of the animals, one male exhibited a hunched posture - all clinical signs subsided by day 3. Necropsy findings were consitent with normal macroscopic background pathathology. Under the conditions of this study the LD50 was determined to be > 2000 mg/kg bw in male/female Sprague-Dawley rats.

Acute Dermal Toxicity (Anon, 1991); An acute dermal toxicity study was performed using a method similar to OECD Guideline for Testing of Chemicals 402 "Acute Dermal Toxicity", and EEC Methods for the determination of toxcity, Directives 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B3. Acute Toxicity (Dermal). The application of of the test item at a single dose of 2000 mg/kg bw to the dorsal skin of 5 rats/sex under occlusive dressing for 24hours did not produce any signs of toxicity and it is concluded that the acute dermal dose LD50 to rats was found to be in excess of 2000 mg/kg bodyweight.

Justification for classification or non-classification

Substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.