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Administrative data

Description of key information

The oral LD50 is > 2000 mg/kb bw. There was no death and no sign of reaction to treatment.

The dermal LD50 is 4100 ± 1300 mg/kb bw. Deaths occured within 24 hours at the highest dose level. The rapidity with which lethality followed was proportional to the dose level applied. Hind limb weakness, and respiratory slowing preceded death by several days in all but one of the rabbits that died.

A study for acute inhataion toxicty is not available. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

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:
4 January 1993 - 2 February 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-conducted and documented study performed according to established guidelines and GLP. Report includes COA of test material.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Young adult rats of the CD strain (remote Sprague-Dawley origin) were supplied by Charles River (U.K.) limited, Margate, Kent, England. The animals were bred under barriered conditions and travelled from the supplier to the animal holding room in sealed boxes with filter protected air-vents. The animals were housed in stainless steel grid cages. Five animals of the same sex were accommodated in each cage.

The animals were held in a limited-access facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18 - 21 °C and a relative humidity range of 38 - 57% R.H. were achieved. Electric tim-switches regulated a lighting cycle of 12 hours of artificial light per day.

A commercially-available complete pelleted rodent diet was fed without restriction except for the removal of food for approximately 18 hours before administration of the test material. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional components, aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contained no antibiotic or other chemotherapeutic or prophylactic treatment. Animals had free access to tap water taken from the public supply. Certificates of analysis were routinely received from the supplier (Suffolk Water Company).
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: not specified in report
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared shortly before administration and any surplus remaining after dosing was destroyed on the same day.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon). The type, time of onset and duration of reactions to treatment were recorded. The test was terminated on the morning of Day 15.
- Necropsy of survivors performed: yes. Each animal was thoroughly examined for abnormality of tissues or organs. All body cavities were opened, larger organs were sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. All abnormalities were described or the normal appearance of major organs was confirmed.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs, see above. The bodyweight of each animal was recorded on theday before dosing and on Days 1, 8 and 15. Histopathology was not performed.
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities at 2000 mg/kg
Mortality:
None in males or females
Clinical signs:
None in males or females
Body weight:
The animals achieved expected bodyweight gains.
Gross pathology:
Necropsy, on Day 15, revealed no significant macroscopic lesions.
Other findings:
None reported.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.
Executive summary:

The acute oral toxicity of the substance was investigated in a group of five male and five felame CD rats at a dosage of 2000 mg/kg. Mortality and signs of reaction to treatment were recorded during a subsequent 14 -day observation period. The animals were killed on the following day and subjected to necropsy.

There was no death and no sign of reaction to treatment. The animals achieved expected bodyweight gains and necropsy revealed no significant macroscopic lesions.

Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The key study was considered reliable without restrictions.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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:
June 1959
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed pre-OECD guidelines and pre-GLP. The methods used are similar to OECD402. There is no information on substance composition in the report, no CoA.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 1.9-2.5 kg
- Fasting period before study: no data
- Housing: individual
- Diet (e.g. ad libitum): ad libitum, rabbot chow and fresh greens
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: entire trunk area
- % coverage: no data
- Type of wrap if used: impervious plastic sleeve contricted at the ends to prevent leakage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess material was removed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): between ± 1-17 grams
- Concentration (if solution): not applicable
- Constant volume or concentration used: no
- For solids, paste formed: no applicable
Duration of exposure:
24 hours
Doses:
0.512, 2.048, 3.072, 4.096, 8.192 g/kg
No. of animals per sex per dose:
From low to high dose: 1, 6, 5, 6, 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweight was determined on day 1 and 14. observations were made of the condition of the skin, the physical apperance of the animal and behavior.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology: the liver, kidney, spleen, skin and lungs of representative rabbits were examined.
Statistics:
No data
Sex:
male
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
Based on:
test mat.
Remarks on result:
other: ± 1300 mg/kg bw
Mortality:
Deaths occured within 24 hours at the highest dose level. The rapidity with which lethality followed was proportional to the dose level applied (see table 1).
Clinical signs:
Hind limb weakness, and respiratory slowing preceded death by several days in all but one of the rabbits that died.
Body weight:
No effects observed.
Gross pathology:
Necropsy revealed no significant gross pathology in the rabbits at any of the 5 treatment levels.
Other findings:
- Histopathology:
Histopathological examinations were made of the livers, kidney, spleens, lungs and the treated skin areas of the 7 rabbits at the critical or lethal levels.
The treated skin areas included subepidermal fibrosis (in the animal at the 3 g/kg) and subepidermal inflammation and necrosis at the 4 and 8 g/kg, the severity increasing with the dosage.
Acanthosis (diffuse epidermal hyperplasia) was seen in one rabbit at 4 and 1 rabbit at 8 g/kg. The latter is regarded a significant adverse finding.
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The LD50 is 4100 mg/kg bw ± 1300.
Executive summary:

23 healthy albino male rabbits weighing 1.9 -2.5 kg were depilated over the entire trunk area. Graded doses of undiluted test material were applied and maintained in contact with the skin by encasing the trunk in an impervious platic sleeve constricted at the end to prevent leakage. Contact was continued for a 24 hour period during which the animals were restrained in stocks. Doses of 0.512, 2.048, 3.072, 4.096, 8.192 g/kg were applied. Bodyweight was determined on day 1 and 14. Observations were made of the condition of the skin, the physical apperance of the animal and behavior.

Deaths occured within 24 hours at the highest dose level. The rapidity with which lethality followed was proportional to the dose level applied (see table 1). Hind limb weakness, and respiratory slowing preceded death by several days in all but one of the rabbits that died. There was no effect on bodyweight. Necropsy revealed no significant gross pathology in the rabbits at any of the 5 treatment levels. Histopathological examinations were made of the livers, kidney, spleens, lungs and the treated skin areas of the 7 rabbits at the critical or lethal levels.

The treated skin areas included subepidermal fibrosis (in the animal at the 3 g/kg) and subepidermal inflammation and necrosis at the 4 and 8 g/kg, the severity increasing with the dosage. Acanthosis (diffuse epidermal hyperplasia) was seen in one rabbit at 4 and 1 rabbit at 8 g/kg. The latter is regarded a significant adverse finding.

The LD50 is 4100 mg/kg bw ± 1300.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 100 mg/kg bw
Quality of whole database:
Reliable with restrictions.

Additional information

There are 2 studies available for acute oral toxicity. Both show very low toxicty. The LD50 from the key study is >2000 mg/kg bw without any mortality or reaction to treatment. This is supported by another study that showed 20% mortality at 32,000 mg/kg bw study and the only reaction to treatment was urinary incontinence.

There is one study available for acute dermal toxicity, the dermal LD50 is 4100 ± 1300 mg/kb bw.

There is no data available for acute inhalation toxicity.

Justification for selection of acute toxicity – oral endpoint

Apparently well conducted GLP study.

Justification for selection of acute toxicity – dermal endpoint

Adequately conducted study.

Justification for classification or non-classification

The oral LD50 is > 2000 mg/kg bw. There was no death and no sign of reaction to treatment. Therefore the substance is not classified for acute oral toxicity.

The dermal LD50 is 4100 ± 1300 mg/kg bw. Therefore the substance is not classified for acute dermal toxicity.

There is no data available for acute inhalation toxicity therefore classification is not possible.