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Administrative data

Description of key information

Oral:
In an acute oral toxicity study in rats the LD50 value of the test substance was determined to be 207 mg/kg bw.
Dermal:
In an acute dermal toxicity study in rabbits the LD50 value of the test item was found to be 429 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Michigan, USA
- Weight at study initiation: 205-262 g


Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
no vehicle used

Doses:
0, 169, 205, 248, 300 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 2.5 and 4 hours after administration and once daily thereafter
- Necropsy of survivors performed: yes
Statistics:
Dose-effects were evaluated using the method developed by Litchfield and Wilcoxon.
Sex:
female
Dose descriptor:
LD50
Effect level:
207 mg/kg bw
Based on:
act. ingr.
95% CL:
197 - 216
Remarks on result:
other: Females were more sensitive than males.
Mortality:
In the 205 mg/kg bw dose group, one male and 2 females died, in the 248 mg/kg bw dose group 2 males and 5 females and in the highest dose group all animals died.
Clinical signs:
Diarrhoe was only observed once in the lowest dose group and occurred more frequently in the higher dose groups. Brown/red staining around the mouth was predominantly observed in the 248 and 300 mg/kg bw test groups, as well as respiratory rates, ataxia and lethargy. Other clinical signs reported were hypothermia, bradypnoea and ocular discharge.
Body weight:
No abnormalities were observed.
Gross pathology:
At necropsy, enlarged and reddened adrenal glands, meningeal haemorrhage, dark reddening of the cortico-medullary junctions in the kidneys, reddened and distended stomachs, reddened intestines, dark purple colouring of the livers and in one case a dark reddening of the lungs were found from the 205 mg/kg bw dose groups onwards.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
207 mg/kg bw
Quality of whole database:
GLP and OECD guideline conform study, reliable and sufficient for assessment

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: study conducted according to GLP and OECD Guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Ohio, USA
- Age at study initiation: young adult
- Weight at study initiation: 2.14-2.99 kg


Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount applied: 0, 172, 337, 660 mg a.s./kg bw





No vehicle used.
Duration of exposure:
24 h
Doses:
0, 172, 337, 660 mg a.s./kg bw
No. of animals per sex per dose:
5, control: 3
Control animals:
other: control animals were treated with deionized water
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweights were recorded on days 0, 7 and 14, the animals were examined for clinical signs 1, 3 and 4 hours after treatment and daily afterwards
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Dose-effects were evaluated using the method developed by Litchfield and Wilcoxon.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
429 mg/kg bw
Based on:
act. ingr.
95% CL:
264 - 627
Mortality:
Mortality occurred in males from the 337 mg/kg bw dose group onwards (two males were found dead). In the highest dose group, 4 males and 3 females died.
Clinical signs:
Decreased defecation was observed in all dose groups. Lethargy, ataxia, decreased respiration rate were observed in the 337 and 660 mg/kg bw dose groups. In the highest dose groups, clear nasal discharge, purulent nasal discharge and a clear wet matting around the mouth were also recorded and one animal appeared emaciated.
Body weight:
During the observation period body weight losses were observed in one animal each from the 337 and the 660 mg/kg bw dose groups.
Gross pathology:
At necropsy the application sites of the rabbits found dead during the observation period was thickened, blanched and subcutaneously haemorrhagic. In some of the animals the brain appeared haemorrhagic and dark red areas and red foci were found in the stomachs. Eschar formation on the skin was observed in the animals of the highest dose group. These animals also exhibited a haemorrhagic thymus. A pale and soft liver as well as soft, spongy and dark reddened kidneys were found in one animal of the highest dose group.
The surviving animals also exhibited a thickened application site and eschar formation. Pale, reddened and pitted kidneys were recorded, but pale kidneys were also observed in the control group. One of the three surviving animals of the highest dose group was found to have white nodules in the lungs and red foci in the stomach.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
429 mg/kg bw
Quality of whole database:
GLP and OECD guideline conform study, reliable and sufficient for assessment

Additional information

Oral

In an acute oral toxicity study the test material was administered orally (by gavage) to male and female Sprague Dawley rats at doses of 0, 169, 205, 248, 300 mg/kg bw. 5 male and 5 female animals were dosed in each dose level and the test material was applied in aqueous solution (33 % w/w). Clinical signs such as ataxia, respiratory distress, lethargy and salivation were observed in all dose groups during the 14 days observation period. Mortality was observed from the 205 mg/kg bw dose group onwards, females were more sensitive than males. At necropsy, the following organs appeared abnormal, mainly due to reddening: kidneys, adrenal glands, brain, liver and intestines. The LD50 was determined to be 207 mg/kg bw.

Dermal

The test material was applied as aqueous solution (33 % w/w) to the skin of male and female New Zealand White rabbits (5 per dose group). The following doses were tested (active ingredient): 0, 172, 337, 660 mg/kg bw. Additionally, 3 male and 3 female control animals were treated with deionized water. The test sites were semi-occlusively covered for a period of 24 hours. During the following 14 days observation period mortality was observed in the 337 and 660 mg/kg bw dose groups. Clinical signs were observed at all dose levels, including dermal responses. Gross findings were seen at necropsy of decedents and terminal kill animals. Based on these results, the LD50 was determined to be 429 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
only one study available

Justification for selection of acute toxicity – dermal endpoint
only one study available

Justification for classification or non-classification

On the basis of the available data for acute toxicity the substance is considered to be classified for acute oral and dermal toxicity into category 3 and labelled with H301 (Toxic if swallowed) and H311 (Toxic in contact with skin) under Regulation (EC) No 1272/2008 (CLP).