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Description of key information

LD50 oral acute rat > 2000 mg/Kg bw (test item)

LD50 dermal acut rat > 2000 mg/Kg bw

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:
April 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not GLP study but good described study
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: First attachments of 30 July 1996 DIRECTIVE 96/54/EC (L 248)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: authorized vendor
- Weight at study initiation: 175 ± 5 g
- Housing: Makrolon cage (48 x 27 x 20 cm), with bedding of wood chips.
- Diet: free access to an experimental diet for rats, provided by an accredited supplier.
- Water: tap water bottles ad libitum
- Acclimation period: 7 days
- Health check: during acclimatation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C (± 2°C).
- Humidity (%): 55% (± 25%)
- Air changes (per hr): 15 air change per hour with filtered air (5 µm)
- Photoperiod (hrs dark / hrs light): 12 hours cycle dark/light
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg for 20 ml of water
- Amount of vehicle : 2 ml of solution for 100 mg of body weight





Doses:
2000 mg/kg
No. of animals per sex per dose:
3 animals per each sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed:
Skin, hair, eyes, mucous membranes, respiratory, circulatory system, central and autonomic nervous system, somatomotor activity and behavior patterns. Particular attention to: tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed
Clinical signs:
no clinical signs observed
Body weight:
no body weight lost
Gross pathology:
no patology observed after necropsy

sacrifice:

All survived animals are killed by CO2 administration

The test was conducted as a limit test, since no mortality was recorded, no further test or analysis are necessary

Interpretation of results:
other: not classified under Regulation 1272/2008
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was tested following Eu Method B1 for acute oral toxicity in rats. Under the epxerimental conditions the LD50 > 1500 mg/kg bw based on active ingredient, LD50 > 2000 mg/kg test item.
Executive summary:

The substance was tested for acute toxicity on Wistar rats following EU Method B1. No signs of toxicity are observed during the experiment at dose of 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
Since November 23,1989 to December
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG
- Age at study initiation: males 11 weeks , females 13 weeks
- Weight at study initiation: males: 256-282 g, females: 199-213 g
- Housing:Individually in Makrolon type-2 cages with standard softwood bedding
- Diet : Pelleted standard Kliba 343, Batch 34/88 rat maintenance diet
- Water : Community tap water from Itingen, ad libitum
- Acclimation period:7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3
- Humidity (%): 40-70 %,
- Air changes (per hr): 10-15 air changes
- Photoperiod: 12 hours cycle dark/light

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 10%
- Type of wrap if used: occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
- Other: On test day 1 the test article was applied evenly on the skin with a syringe

REMOVAL OF TEST SUBSTANCE
- Washing : lukewarm tap water


TEST MATERIAL
- Amount(s) applied: 4 ml
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
4 ml at 2000 mg/kg bw
No. of animals per sex per dose:
5 x sex x single dose
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations :
mortality/ viability: Four times during test day 1, and daily during days 2 - 15
Body Weights: Test days 1 (pre-administration), 8 and 15.
Symptons: Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

GENERAL BEHAVIOR
aggressiveness vocalization, restlessness/excitation nervousness, fear sedation, somnolence, sleep, coma

RESPIRATION
apnea ,dyspnea ,rales

EYE
chromodacryorrhea, exophthalmos, miosis, mydriasis, whitish discharge, lid adhesion, negative corneal reflex

NOSE
rhinorrhea, epistaxis

MOTILITY
akinesia, ataxia ,dropped head, hyperkinesia, hypokinesia, paralysis, flaccid paralysis, spastic , paddiing movements, stiff gait, rolling movements

BODY POSITION
ventral body position
latero-abdominai position
hunched posture

MOTOR SUSCEPTIBILITY
spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus retching, "Straub" phenomenon ,tremor ,muscle-twitching ,muscle-twitching, generalized

SKIN
erythema edema, necrosis ,crusts ,scale formations

VARIDUS
loss of weight ,emaciation ,diarrhea ,ruffled fur ,necrosis of tissue of application area , salivation ,pallor, cyanosis


Test item preparation:
The test article was placed into a glass beaker on a tared Mettler PK 300 balance and the vehicle (distilled water) was added. A weight/volume dilution was prepared using .a homogenizer.
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer.
The preparation was made immediately prior to dosing.
Statistics:
The LOGIT-Model couid not be applied to the observed rate of death. The toxi¬city was estimated without use of a statistical model.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed during the test
Clinical signs:
at 2000 mg/kg: erythema, brown discolored application area, scales (females).
The described symptoms were partly observed until termination of test. No systemic symtoms were observed.
Body weight:
normal
Gross pathology:
No macroscopic organ changes.
Interpretation of results:
other: not classified under Regulation 1272/2008
Conclusions:
The analogue substance was tested for acute dermal toxicity following OECd 402. Under the experimental conditions the LD50 (LD0) > 2000 mg/kg bw.
Executive summary:

The test article was applied to the skin of rats of both sexes for 24 hours at a dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg.

Based on these observations, the LOGIT model could not be applied to the observed rate of death.

Therefore, the toxicity was estimated to be greater than 2000 mg/kg

SYMPTOMS

The following local findings were observed: 2000 mg/kg: erythema, brown discolored application area, scales (females). The described symptoms were partly observed until termination of test. No systemic symtoms were observed.

NECROPSY

The following macroscopic organ changes were observed: No macroscopic organ changes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral exposure pattern is covered by studies on the substance, dermal toxicity is assessed through a very similar substance, and inhalation is not considered as a potential exposure pattern based on the vapour pressure. The oral toxicity has been performed just as a limit test at 2000 mg/Kg bw on the test item, with no effects, it can be concluded that the substance does not arise any concern for acute toxicity by oral route.

For acute dermal toxicity, no studies are available on the substance. A study has been performed on a very similar substance and the results have been taken into account for the assessment. The analogue substance was tsted for acute dermal toxicity and the LD50, LD0 resulted > 2000 mg7kg. Based on the read across considerations same results apply to the target substance.

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), table 3.1.1, Acute toxicity hazard categories and acute toxicity estimates (ATE) defining the respective categories:

For Acute toxicity oral route:

Category 1: ATE <= 5 mg/kg bw

Category 2: 5 < ATE <= 50 mg/kg bw

Category 3: 50 < ATE <= 300 mg/kg bw

Category 4: 300 < ATE <= 2000 mg/kg bw

The LD50 of the test substance was determined to be mroe than  2000 mg/kg bw in the chosen reference test, which is outside the above criteria. Therefore, the test substance is not classified for Acute toxicity by oral exposure.

According to the CLP Regulation (EC n. 1272/2008), table 3.1.1, Acute toxicity hazard categories and acute toxicity estimates (ATE) defining the respective categories:

For Acute toxicity dermal route:

Category 1: ATE <= 50 mg/kg bw

Category 2: 50 < ATE <= 200 mg/kg bw

Category 3: 200 < ATE <= 1000 mg/kg bw

Category 4: 1000 < ATE <= 2000 mg/kg bw

The LD50 of the test substance was determined to be more than 2000 mg/kg bw in the chosen reference test, which is outside the above criteria. Therefore, the test substance is not classified for Acute toxicity by dermal exposure.