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Description of key information

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:
16.4-30.4.2002
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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: Ace Animals, Inc., Boyertown, PA
- Age at study initiation: Young adult (9-10 weeks)
- Weight at study initiation: males 201-236 grams and females 137-184 grams
- Fasting period before study: app. 19 hours
- Housing: singly housed in suspended stainless steel caging with mesh floors.
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Filtered tap water
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23 'C (animal room)
- Photoperiod (hrs dark / hrs light): 12 hour cycle
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% w/w solution in distilled water.
- Amount of vehicle (if gavage): calculated based on the initial bodyweights
Doses:
Each animal received 5.000 mg/kg of the test substance, administered using a stainless steel ball-tipped gavage needle attached to an appropriate syringe.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity and behavioral changes at 1 and 3 hours post-dosing and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observationis of tremours, convulsions, salivation, diarrhea and coma. Individual bodyweights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination).

- Necropsy of survivors performed: Gross necropsis were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survived
Body weight:
All animals gained weight during the study.
Gross pathology:
No gross abnormalitites
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
All animals survived, gained weight and appeared active and healthy. Apart from all animals exhibiting black colored feces on Day 1, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. Gross necropsy findings at terminal sacrifice were unremarkable.
Under the conditions of this study, the single dose acute oral LD50 of the substance is greater than 5.000 mg/kg of bodyweight in male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from August 21, 2007 to Septamber 20, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was carried out in accordance with internationally valid GLP principles.
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeding farm BioTest s.r.o., Konarovice, 281 25, Czech Republic,
- Weight at study initiation: 211 – 254 g
- Housing: animal room with monitoring conditions – one animal in one plastic cage
- Diet (e.g. ad libitum): ST 1 BERGMAN – complete pelleted diet ad libitum
- Water (e.g. ad libitum): drinking tap water ad libitum
- Acclimation period: 8 days
- Bedding: sterilized shavings of soft wood
- Randomisation: according to the internal rule, at the start of the study the weight variation of animals was minimal and did not exceed + 20 % of the mean weight
- Identification of animals: colour marks on tail, each cage was marked with the number of study, number of animal, sex, name and dose of the test
substance
- Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, during the acclimatisation period and before the start of study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 22 +/- 3°C, permanently monitored
- Humidity (%): relative humidity 30 – 70 %, permanently monitored
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark
Type of coverage:
occlusive
Vehicle:
other: No vehicle, the substance was moistened with the smallest amount of water
Details on dermal exposure:
TEST SITE
- Area of exposure: 6x6 cm
- % coverage: 10%
- Type of wrap if used: covered by mull, plastic foil and held in contact by plaster (strapping)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The substance was tested as such, moistened with the smallest amount of water. 2000 mg/kg

VEHICLE
no vehicle
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
10 animals: 5 females+ 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Observation: the first day: twice (30 minutes and 3 hours after application), the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, nutritive condition, autonomic and central nervous systems, psychic activity, somatomotor activity, reactions to stimuli, function of respiratory, circulatory, digestive and urogenital system. Also presence of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma was carefully observed.
Weighing: The animals were weighed at the start of the study (before application), at 8th day and in the end of experiment (15th day). Average body weight in-group was counted from individual body weights.
- Necropsy of survivors performed::
All test animals survived to the end of study were sacrificed on the 15th day by injection of veterinary preparation T61 (1 ml iv.) and gross necropsy was carried out. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated.
Preliminary study:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality
Clinical signs:
Without clinical changes
Body weight:
Weight increments in all animals were in physiological range.
Gross pathology:
No death of animals was observed during 14 days observation period.
Macroscopic changes were diagnosed during pathological examination in two animals (Lungs – dark red punctiform strata). In one male viscous content of intestine (diarrhoea) and in one female dilatation of uterus (demonstration of oestrus cycle) were found out.

Pathological examination  2000 mg/kg males 

Animal No.

         

Findings

1

Without pathologic changes

2

Lungs: dark red punctiform strata

3

Lungs: dark red punctiform strata

4

Without pathologic changes, (viscous content of intestine)

5

Without pathologic changes

Pathological examination  2000 mg/kg females

 

Animal No.

         

Findings

1

Without pathologic changes

2

Without pathologic changes

3

Without pathologic changes, (Uterus – dilatation, demonstration of oestrus cycle)

4

Without pathologic changes

5

Without pathologic changes

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

The test was performed according to the Method B.3 Acute Toxicity (Dermal), Directive 92/69/EEC, published in OJ L 383A, 1992.

The test substance was tested for the assessment of acute dermal toxicity using Wistar rats.

The study was performed as limit test: two groups of animals - 5 males and 5 females and the dose of 2000 mg/kg. The test substance was applied on the shaved skin of the test animals in delivered form (moistened with the smallest amount of water) for 24 hours.

The test animals were observed 14 days after application, afterwards were sacrificed and the necropsy for macroscopic examination of the organs was performed.

The test substance applied in dose 2000 mg/kg did not cause the death of animals. No clinical signs of toxicity were observed during the study in all animals. Macroscopic changes were diagnosed during pathological examination in two animals (lungs – dark red punctiform strata).

According to the results of study the value of LD50 dermal of the test substance for rats of both sexes is higher than 2000 mg/kg.

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

Additional information

One GLP study for acute toxicity exist for the substance in which the LD50 for rat was shown to be >5000 mg/kg bw.

The results for acute toxicity after dermal administration is based on read-across from a GLP study on the source substance Humic acids, potassium salt, in which the LD50 for rats was shown to be >2000 mg/kg bw. A justification document for read-across is attached to the dossier.

Inhalation exposure for humans is unlikely and a study has not been performed.

Justification for classification or non-classification

Based on experimental results it is concluded that the substance shall not be classified as acute toxic according to CLP.

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