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Administrative data

Description of key information

Two GLP guideline studies are available for the oral and dermal route.

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:
June 21, 1990 to July 05, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: males: about 8 weeks, females: about 10 weeks
- Weight at study initiation: males: 188 g, females: 179 g (mean deviation < 20 % for both)
- Fasting period before study: 16 hours before and up to 4 hours after application
- Housing: groups of 5 under conventional conditions
- Diet: fixed-formula standard diet
- Water: ad libitum
- Acclimation period: 6 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 50 ± 10 %
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark/hrs light): 12 hrs dark/12 hrs light
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): Constant application volume = 10 ml/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspection: twice daily (once on weekends and holidays), several times on day of administration; weighing: once a week until end of observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the 14-day observation period.
Clinical signs:
After single administration of 2000 mg/kg no clinical signs were observed.
Body weight:
Growth was not retarded in male and female rats.
Gross pathology:
There were no gross pathological findings in any of the male and female animals of the dose 2000 mg/kg sacrificed at the end of study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the observation that no acute toxic effects were observed during the present study the test item is not classified.
Executive summary:
In an acute oral toxicity study, groups of 8 week old male and 10 week old female Wistar rats (5/sex) were given a single oral dose of the test item in polyethylene glycol 400 at 2000  mg/kg bw and observed for 14 days.

No mortality occurred at the limit dose of 2000 mg/kg bw.

The test item not classified toxic based on a LD0 2000 mg/kg.

There were no treatment related clinical signs, necropsy findings or changes in body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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
Study period:
1991-01-17 to 1991-01-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
For logistic reasons (application as paste) and the short period between preparation and application no analytical examination of the stability of the sample in the formulation was conducted.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen (Germany)
- Age at study initiation: 9 weeks (m); 13 week (f)
- Weight at study initiation: 230 g (m); 204 g (f)
- Housing: Makrolon cages Type II on non-dusty wood pellets
- Diet (e.g. ad libitum): Fixed-formula standard diet, Altromin 1324 pellets (Altromin GmbH und Co KG, Lage) ad libitum
- Water (e.g. ad libitum): Potable water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 50 ± 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
castor oil
Remarks:
Cremophor EL
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flanks
- % coverage: 10 %
- Type of wrap if used: Fermoflexband, Beiersdorf AG

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): No data
- Lot/batch no. (if required): No data
- Purity: No data
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly (day 1, 8 and 15)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
During the observation period none of the animals died. The growth of male animals was not affected. The females' body weight slightly decreased in the first week of observation. At the end of the experiment none of the killed animals showed pathological-anatomical findings.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
During the testing no mortalities occurred.
Clinical signs:
No systemic symptoms of poisoning were observed.
No local skin alterations that could be attributed to the test sample were observed.
From the beginning of the experiment, crystallised residues of the substance were partly sticking to the skin, causing skin lesions at the time the bandage was removed. The effect occurred in 4 of 5 male and 5 of 5 female animals and continued until day 12.
Body weight:
The body weight of female animals slightly decreased during the first week of observation.
Gross pathology:
No apparent pathological findings were observed during the experimental period.
Other findings:
No other findings.

Bodyweights of male and femal rats:

Male

Female

Animal

Day

Animal

Day

1

8

15

1

8

15

1

233 g

248 g

276 g

1

206 g

197 g

202 g

2

225 g

234 g

259 g

2

207 g

202 g

209 g

3

231 g

244 g

262 g

3

203 g

199 g

204 g

4

234 g

243 g

276 g

4

200 g

196 g

202 g

5

229 g

240 g

266 g

5

205 g

199 g

204 g

Av.

230 g

242 g

268 g

Av.

204 g

199 g

204 g

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study in rat according to EU method B.3, no mortality or clinical signs were reported up to a limit dose of 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study, groups of young adult Wistar rats (5 male and 5 female) were dermally exposed to the test item (95.7 %) in Cremophor EL paste for 24 hours applied on 10 % of body surface area at a dose of 2000 mg/kg bw. Animals were then observed for 14 days.

No mortality occurred in limit the test at a concentration of > 2000 mg/kg bw both in male and female rats.

The test item is not classified following CLP Annex I based on the exceeded limit dose of 2000 mg/kg bw for male and female rats.  

Systemic poisoning was not observed. Local skin alterations did not appear. When removing the coverage, skin lesions occurred. The lesions were not considered substance related. The growth of male and female rats was not affected. Female animals slightly lost weight during the first week of observation. No mortalities occurred. At the end of the 14 days of observation all of the killed animals were without pathological findings.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

No mortality has been reported after administration of the test item at a limit dose of 2000 mg/kg bw by oral gavage or dermal exposure, respectively, in reliable GLP guideline studies.


Justification for selection of acute toxicity – oral endpoint
OECD GLP guideline study

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study

Justification for classification or non-classification

No mortality has been reported after administration of the test item at a limit dose of 2000 mg/kg bw by oral gavage or dermal exposure, respectively, in reliable GLP guideline studies.