Registration Dossier

Administrative data

Description of key information

Oral exposure
In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 420, the LD50 of the test material was calculated by exposing 4 females Wistar rats to a dose of 2000 mg/kg of body weight by oral gavage. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.
Dermal exposure
In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 402, the LD50 of the test material was calculated by exposing 5 males and 5 females Wistar rats to a dose of 2000 mg/kg of body weight by contact. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
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
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of et least five dayx the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previous dosed animals.
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to for hours after dosing, free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to acheive limits of 19 to 25°C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchenge was at least fifteen changes per hour and the ligjting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain anay contaminant of a level that might have affected the purpose or integrity of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage using a metin cannula attached to a graduated syringe. The volume administered to each animal was calculated according to ist fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
Clinical observations were made 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorder on day 0 and on days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Preliminary study:
Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the strating dose.
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals was treated.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animals was killed in extremis one day after dosing
Clinical signs:
Signs of systemic toxicity noted were hunched posture, pilo-erection, ataxia, tiptoe gait, lethargy, decreased respiratory rate, laboured respiration, dehydration and hypothermia.
Surviving animals appeared normal one, two, eight or thirteen days after dosing.
Body weight:
Surviving animals showed expected gains in bodyweight during the study, except for one animal which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
Patchy pallor of the liver animal was noted at necropsy of the animal that was killed in extremis. No abnormalities were noted at necropsy of animals that were killed at the end of the test.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 420, the LD50 of the test material was calculated by exposing 4 females Wistar rats to a dose of 2000 mg/kg of body weight by oral gavage. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
1 (reliable without restriction)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
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
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Species:
rabbit
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of et least five dayx the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The animal weighted at least 200g, and the bodyweight variation did not exceed ± 20% of the mean bodyweight for female animals. For male animals, the bodyweight variation of one male did exceed ↑1 20% of the mean bodyweight. This deviation from the Standard test Method was considered not to affect the purpose or intergrity of the study.

The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
The animals were housed individually during the 24-hour exposure period and in groups of up to four, by sex, for the remainder of the study. Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to acheive limits of 19 to 25°C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchenge was at least fifteen changes per hour and the ligjting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain anay contaminant of a level that might have affected the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair.
The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
Duration of exposure:
The animals were caged individually for the 24-hour exposure period and for the remainder of the test.
Shortly after dosing the dressings were examined to ensure that they were securely in place.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
The animals were observed for overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity/mortality inspections were also performed twice daily, eraly and late, during normal working days and once daily at weekends.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored.
Individual bodyweights were recorder on day 0 and on days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Preliminary study:
No mortalities were noted after the 24-hour contact period in one male and one female
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no death
Clinical signs:
There were no signs of systemic toxicity.
There were no signs of dermal irritation.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found greater than 2000 mg/kg bodyweight.
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 402, the LD50 of the test material was calculated by exposing 5 males and 5 females Wistar rats to a dose of 2000 mg/kg of body weight by contact. Under the conditions of the test no systemic signs of toxicity were reported over a period of 14 days and the LD50 was determined to be > 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
1 (reliable without restriction)

Additional information

Oral and dermal exposure conducted to the same result: LD50 > 2000 mg/kg.

The test material does not classification under Regulation 1272/2008.


Justification for selection of acute toxicity – oral endpoint
The two studies were conducted under the same guidelines and under GLP.
The "oral 002" study is retained just because it is more recent.

Justification for classification or non-classification

Oral and dermal exposure conducted to the same result: LD50 > 2000 mg/kg