Registration Dossier

Administrative data

Description of key information

Under the conditions of the study in rats according to OECD 401 the acute toxicity after oral application is greater than 2000 mg/kg bw. for the test item (Hüls AG, 1996). Furthermore an acute dermal toxicity study was conducted in rats according to OECD 402 revealed LD50 of greater than 2000 mg/kg bw (Hüls AG, 1996). An inhalation acute toxicity study is not available for the test substance.

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:
1996-03-25 to 1996-04-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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: Harlan Winkelmann GmbH, 33176 Borchen, Germany
- Strain: HsdCpb: WU (SPF)
- Sex. male and female
- Weight at study initiation: male: 129 - 160 g, female: 126 - 137
- Fasting period before study: 16 hours
- Housing: max 5 animals per sex per cage
- Diet (e.g. ad libitum): Ssniff R 10, complete feed for rats, Ssniff Spezialfutter GmbH, 59494 Soest, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark rhythm

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
ADMINISTRATION: 
- Doses per time period: single dose (gavage)
- Volume administered or concentration: 2.110 ml/kg bw ml/kg bw
- At first test item were administrated to 2 male and 2 femal rats, there were no mortality after 24 hours, test item were administrated to 3 male and 3 female rats
Doses:
Limit test: 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
EXAMINATIONS:
- Body weights: days 0, 7, and 14
- Clinical signs and mortality: 1/2, 1, 2, 3, 4, 5, 6 hours after  treatment, thereafter daily
- Necropsy: all animals (macroscopic)
- Post dose observation period: 14 days
Statistics:
not required
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred. 
Clinical signs:
No signs of toxicity were observed in 3 males and 4  females. 
Other animals: - 2-4 hours after treatment: Abnormal gait, crouched posture, slight  sedation and ataxia, piloerection, slight hypothermia (1 male, 1 female),  bloody lacrimation (1 male). - 5 hours after treatment: No more symptoms
Body weight:
Body weight gain was not affected.
Gross pathology:
No evidence of macroscopically discernible organ  changes was found.
Other findings:
no other findings

no other information

Conclusions:
Under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.
Executive summary:

The test item (2000 mg/kg bw) was given to rats by oral administration to obtain information on the toxicity, in particular lethality, of the test item.

The test item was administrated oral to 5 male and 5 female WISTAR rats.

No signs of toxicity were observed in 3 males and 4  females.  2 males and 1 female showed 2 -4 hours after treatment following symptoms: abnormal gait, crouched posture, slight  sedation and ataxia, piloerection, slight hypothermia (1 male, 1 female),  bloody lacrimation (1 male). 5 hours after treatment there were no more symptoms.

There was no influence on the increase in body weight.

Dissection at the end of the experiment revealed no evidence of macroscopically discernible organs.

Under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is a guideline study with Klimisch score 1 (reliable without restrictions).

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:
1996-04-15 to 1996-05-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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: Harlan Winkelmann GmbH, 33176 Borchen, Germany
- Strain: HsdCpb: WU (SPF)
- Sex. male and female
- Weight at study initiation: male: 251-274 g, female: 209-233 g
- Housing: single
- Diet (e.g. ad libitum): Ssniff R 10, Ssniff Spezialfutter GmbH, 59494 Soest, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / light rhythm
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
ADMINISTRATION: 
- Area covered: dorsolumbar region, approximately 10 % of the body surface
- Doses: single dose, 2.110 ml/kg bw
- Occlusion: gauze dressing fixed with Acrylastic bandage (semiocclusive)
- Removal of test substance: after 24 hours with corn oil (MEH 56) and  cellulose
- At first test item were administrated to 2 male and 2 femal rats, there were no mortality after 24 hours, test item were administrated to 3 male and 3 female rats
Duration of exposure:
24 hours
Doses:
single dose: 2.110 ml/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
EXAMINATIONS: 
- Clinical signs, mortality: 1/2, 1, 2, 3, 4, 5, and 6 hours after  treatment, once daily for next 2 weeks
- Dermal response: Daily after patch removal
- Body weights: days 0, 7, and 14
- Macroscopic examination: day 14 (all animals)
Statistics:
not required
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
No signs of toxicity were observed. No erythema or edema  were observed from patch removal to end of study.
Body weight:
Body weight gain was not affected.
Gross pathology:
No macroscopic changes in organs, skin, or  subcutaneous tissue were found.
Other findings:
no other findings

no other information

Conclusions:
Under the conditions of this study the LD50 of the acute dermal toxicity on male and female rats is above 2000 mg/kg of body weight for the test item in rats.
Executive summary:

The test item was applicated at the skin of the male and female rats in a dose of 2000 mg/kg body weight

to obtain information on the toxicity, in particular lethality, of the test item.

The test item was administrated dermal to 5 male and 5 female WISTAR rats.

No mortalities were observed at this dose. No signs of toxicity were observed. No erythema or edema  were observed from patch removal to end of study.

Body weight gain was not affected.

No macroscopic changes in organs, skin, or  subcutaneous tissue were found.

Hence the LD50 of the acute dermal toxicity on male and female rats is above 2000 mg/kg of body weight for the test item in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is a guideline study with Klimisch score 1 (reliable without restrictions).

Additional information

Justification for classification or non-classification

Based on the results of the oral and dermal acute studies in rats and according to the EC Regulation 1272/2008 the test substance must not be classified.