Registration Dossier

Administrative data

Description of key information

(LD50 (oral, rat) > 2000 mg/kg bw: no clinical findings, no mortality
LD50 (dermal, rat) > 2000 mg/kg bw: no clinical findings, no mortality

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: study report in brief, but sufficient information aviailable to be taken for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Single oral application of 1000 and 5000 mg/kg bw Nigrosin WLF to groups of 10 female Wistar rats dissolved in water and observed over a period of 14 daxs for clinical signs and mortality.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation:150-200 g
- Diet ad libitum
- Water ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Single oral application of 1000 and 5000 mg/kg bw Nigrosin WLF to groups of 10 female Wistar rats dissolved in water and observed over a period of 14 daxs for clinical signs and mortality.
Doses:
1000 or 5000 mg/kg bw
No. of animals per sex per dose:
10 per dose group
Control animals:
no
Details on study design:
Single oral application of 1000 and 5000 mg/kg bw Nigrosin WLF to groups of 10 female Wistar rats dissolved in water and observed over a period of 14 daxs for clinical signs and mortality. Results evaluated by Probit-analysis according to Fink and Hund, arneimittelforschung 15, 1965
Statistics:
Results are evaluated by Probit-analysis according to Fink and Hund, Arzneimittelforschung 15, 1965
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: no mortality, fo clinical findings
Mortality:
no animal died
Clinical signs:
mo clinical signs wre observed
Body weight:
mean body weight development was not affected by treatment
Gross pathology:
no data
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

An acute oral toxicity study is available with single oral application of 1000 and 5000 mg/kg bw Nigrosin WLF to groups of 10 female Wistar rats dissolved in water and observed over a period of 14 days for clinical signs and mortality. No animal died , no clinical signs were observed and body weight development was not affected by treatment. Thus the LD50 is >5000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The study is performed similiar to the current guideline and has Klimisch Score 2

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: Guideline study and GLP
Qualifier:
according to
Guideline:
other: OECD TG 402 and EEC Directive 440/2008 Part B, Method B.3
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9-13 weeks
- Weight at study initiation:
males 291-300 g
females 226-247 g
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%):55
- Air changes (per hr) 10:
- Photoperiod (hrs dark / hrs light): 12/12




Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was applied to a wet gauze layer which was then applied to the shaved area of the back of the rabbits. The patches were held in place by semi-occlusive dressing (gauze strip and a tape). After 24 hours the dressings were removed and the area was rinsed with tepid water
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
other: the opposite site of the back of each animal served as control
Details on study design:
The test substance was applied to a wet gauze layer which was then applied to the shaved area of the back of the rabbits. The patches were held in place by semi-occlusive dressing (gauze strip and a tape). After 24 hours the dressings were removed and the area was rinsed with tepid water. The opposite site of the back of each animal served as control. Animals were observed for clinical signs and mortality for 14 days, weight gain was checked weekly. after termination of the observation period the animals were sacrificed and examind macroscopically
Statistics:
Only the limit dose was tested
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Remarks on result:
other: no death occurred and no clinical signs were reported
Mortality:
no animal died
Clinical signs:
no clinical sign is reported
Body weight:
no effect on weight development
Gross pathology:
no gross pathological f9nding
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Executive summary:

Nigrosin WLF was applied dermally to the shorn back and flank of groups of male and female Wistat rats at a dose of 2000 mg/kg bw under semiocclusive conditions. After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry. The dose of 2000 mg/kg bw was tolerated by male and female rats without mortalities or toxcolological relevant clinical signs. No adverse effects on body weight development in males and females nor gross pathological findings were observed. Thus, the LD50( rat, dermal) is > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
the study is a guideline study and is GLP compliant and has Klimisch Score 1

Additional information

ORAL APPLICATION

An acute oral toxicity study is available with single oral application of 1000 and 5000 mg/kg bw Nigrosin WLF to groups of 10 female Wistar rats dissolved in water and observed over a period of 14 days for clinical signs and mortality. No animal died , no clinical signs were observed and body weight development was not affected by treatment. Thus the LD50 is >5000 mg/kg bw

DERMAL APPLICATION

Nigrosin WLF was applied dermally to the shorn back and flank of groups of male and female Wistat rats at a dose of 2000 mg/kg bw under semi-occlusive conditions. After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry. The dose of 2000 mg/kg bw was tolerated by male and female rats without mortalities or toxcolological relevant clinical signs. No adverse effects on body weight development in males and females nor gross pathological findings were observed. Thus, the LD50( rat, dermal) is > 2000 mg/kg bw

INHALATION ROUTE

According to Regulation /EC) No. 1907/2006 ANNEX VIII column 2: In addition to the acute toxicity study using the oral route, for substances other than gases, at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an other study available using the dermal route: this study is performed according to respective guideline and is GLP compliant and evaluated with Klimisch Score 1. Thus, there is no need to conduct an acute toxicity study using the inhalation route..


Justification for selection of acute toxicity – oral endpoint
the only available study which is performed similiar to the current guideline

Justification for selection of acute toxicity – inhalation endpoint
According to Regulation /EC) Mo. 1907/2006 ANNEX VIII colun 2: In addition to the acute toxicity study using the oral route, for substances other than gases, at least the acute toxicity data for one other route should be provided. This recommendation is fulfilled because there is an other study available using the dermal route: this study is performed according to respective guideline and is GLP compliant and evaluated with Klimisch Score 1. Thus, there is no need to conduct an acute toxicity study using the inhalation route.

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

Justification for classification or non-classification

Based on the available data no classification or labelling is required