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Description of key information

A valid acute oral toxicity study and a valid acute dermal toxicity study are available.

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: Comparable to guideline study with acceptable restrictions (e.g. rel. low purity of test substance 86.3%)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Bor: WISW (SPF Cpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 6 to 8 week old
- Fasting period before study: 16 h
- Housing:separated by sex, max. 5 animals per Makrolon type III cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:at least 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod: 12hrs dark / 12hrs light


I
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30g/100cm3
- Amount of vehicle (if gavage):6.67 cm3/kg body weight
- Justification for choice of vehicle: corn oil was chosen because of low water solubility of test substance


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 1/2, 1, 2, 3, 4, 5, and 6 h post application, once daily during the following 14 days
- Frequency of observations and weighing: day 0, day 7, day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
preliminary study: 2 males and 2 females were orally administered with 2000 mg/kg bw test substance
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
5 - 6 h post applicationem bei drei von fünf männlichen
Tieren kurzzeitig Diarrhoe. Ein weibliches Tier zeigte zu
diesem Zeitpunkt Hockhaltung und ein gesträubtes Fell. 24
und 48 h post applicationem wurde lediglich bei einem Tier
noch ein gesträubtes Fell beobachtet, 72 h post
applicationem war das Tier symptomfrei. Zwei männliche und
vier weibliche Tiere zeigten während der gesamten
Beobachtungsperiode keine Vergiftungssymptome. Die
Körpergewichtsentwicklung der Tiere während der gesamten
Versuchsdauer war normal.

"ENGLISH"

5 up to 6 hours after the application three of five male
test animals showed diarrhoe for a short time. A female
animal showed crouched posture and piloerection. 24 and 48
hours after the application only one animal showed
piloerection and 72 hours after the application the animal
was free of all symptoms. Two male as well as four female
animals showed no symptoms of toxicity during the whole
observation period. The body weight gain of the animals
developped normally during the whole test period.
Gross pathology:
Effects on organs:
Die Sektionen und makroskopischen Untersuchungen der Organe
am Versuchsende ergaben keine Hinweise auf substanzbedingte
Organveränderungen. Es wurden keine geschlechtsspezifischen
Toxizitätsunterschiede festgestellt.

"ENGLISH"

The sections and macroscopic investigations of the organs at
the end of the test showed no indications of substance
related changes of the organs and no sex-specific
differences in toxicity.

Mortality: males: 0/5, females 0/5

Clinical signs:

Five and six hours after the application three of five males showed diarrhea. A female animal showed squatting position and rough coat 5 and 6 h after application, and rough coat after 48 h. After 72 hours the animal was free of all symptoms. Two males as well as four females showed no symptoms of toxicity during the whole observation period.

The body weight gain of the animals developed normally during the whole test period.

Necropsies and gross pathology: no evidence of substance-related organ changes was found

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 was >2000 mg/kg bw.
Executive summary:

In a rat study, which was done under GLP and according to OECD guideline 401, the oral LD50 was >2000 mg/kg bw (Hüls AG 1992a). No effects were observed with regard to mortality, body weight gain and gross examinations. Three male rats showed diarrhoea five and six hours after application. One female showed squatting position and rough coat 5 and 6 hours after the application. After 48 hours only the rough coat was still present and no effects were seen after 72 hours. The other animals showed no symptoms of toxicity during the whole observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (e.g. rel. low purity of test substance 86.3%)
Qualifier:
according to
Guideline:
other: OECD 402
GLP compliance:
yes
Test type:
other: acute dermale toxicity
Limit test:
yes
Species:
rat
Strain:
other: Bor: WISW (SPF Cpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: Winkelmann Co, 4799 Borchen
- Weight at study initiation: 200-300 g
- Fasting period before study:
- Housing:separated by sex, max. 5 animals per Makrolon type III cage
- Diet:ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (12hrs dark / 12hrs light)


Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: intact dorsal skin, 6.67 cm3/kg bw
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with corn oil MEH 56


Duration of exposure:
4 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 1/2, 1, 2, 3, 4, 5, and 6 h post application as well as once daily during the following 14 days
- Frequency of observations and weighing: day 0, day 7, day 14
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
Substanzbedingte Vergiftungssymptome traten nicht auf. Alle
Tiere zeigten während der 14tägigen Beobachtungsperiode eine
normale Körpergewichtsentwicklung.
"ENGLISH"
No substance related symptoms of toxicity occured. All
animals showed a normal body weight development during the
observation period.
Gross pathology:
Effects on organs:
Keine Hinweise auf substanzbedingte Organveränderungen bei
den Sektionen und makroskopischen Untersuchungen.
"ENGLISH"
No indications of substance related changes of the organs
occured during the sections and macroscopic investigations.
Other findings:
Signs of toxicity (local):
Es traten weder bei den männlichen noch bei den weiblichen
Tieren substanzbedingte Vergiftungserscheinungen auf. Im
Applikationsbereich wurde 72 h nach Substanzverabreichung
bei drei weiblichen Tieren Schuppenbildung auf der Haut
beobachtet; zwei Tiere zeigten zusätzlich eine Hautrötung.
Nach Ablösung der Schuppen am 7. Tag post applicationem (2
Tiere), am 9. Tag post applicationem (1 Tier) stellte sich
die Applikationsfläche ohne Befund dar. Fünf männliche und
zwei weibliche Tiere zeigten zu keinem Beobachtungszeitpunkt
eine Hautveränderung.

"ENGLISH"
Neither the male nor the female animals showed substance
related symptoms of toxicity.
72 hours after the application of the substance three female
test animals showed scale formation of the skin in the
application range; two animals showed as well redness of the
skin. After the scales came off after the application
(7. day 2 animals, 9. day 1 animal the treated area was
without any findings. Five male and two female animals never
showed changes of the skin during the observation period.

Mortality:

Male: 2000 mg/kg bw; 0/5; females 0/5

Clinical Signs:

No substance related symptoms of toxicity occured. All animals showed a normal body weight development during the observation period.

Gross pathology:

No indications of substance related changes of the organs occured during the sections and macroscopic investigations.There were no changes of the skin or in the subcutaneous tissue in the region of application.

Other findings:

72 hours after the application of the substance three female test animals showed scale formation of the skin in the application range; two animals showed as well redness of the skin. After the scales came off after the application (7. day 2 animals, 9. day 1 animal the treated area was without any findings. Five male and two female animals never showed changes of the skin during the observation period.

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 after dermal exposure was >2000 mg/kg bw.
Executive summary:

In rats the LD50 after dermal exposure was >2000 mg/kg bw. This dermal acute toxicity study was done under GLP according to OECD guideline 402 (Hüls AG 1992b). No effects were observed with regard to mortality, clinical signs, body weight and gross examinations. However, scale formation in the region of application was observed in three of five animals 72 hours post application. This effect was reversible within 9 days. In addition, two of these animals showed skin redness 72 hours after the application. Although,

no changes of the skin or in the subcutaneous tissue in the application area were found in any of the animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP guideline study

Additional information

Acute toxicity: oral

In a rat study, which was done under GLP and according to OECD guideline 401, the oral LD50 was >2000 mg/kg bw with the test substance Vulcuren (purity: 86.3%, Hüls AG 1992a). No effects were observed with regard to mortality, body weight gain and gross examinations. Three male rats showed diarrhoea five and six hours after application. One female showed squatting position and rough coat 5 and 6 hours after the application. After 48 hours only the rough coat was still present and no effects were seen after 72 hours. The other animals showed no symptoms of toxicity during the whole observation period.

Acute toxicity: inhalation

There are no data available.

Acute toxicity: dermal

In rats the LD50 after dermal exposure was >2000 mg/kg bw test substance Vulcuren (purity: 86.3%). This dermal acute toxicity study was done under GLP according to OECD guideline 402 (Hüls AG 1992b). No effects were observed with regard to mortality, clinical signs, body weight and gross examinations. In three females scale formation in the application area was observed 72 after exposure. This effect was reversible within 9 days. In addition, two of these animals showed skin redness 72 hours after the application. However, no changes of the skin or in the subcutaneous tissue in the application area were found in any of the animals evaluated.

Acute toxicity: other routes

There are no data available.

Human information

There are no human data available.


Justification for selection of acute toxicity – oral endpoint
key study is used (only available study).

Justification for selection of acute toxicity – dermal endpoint
key study is used (only available study).

Justification for classification or non-classification

The data from the acute oral and acute dermal studies showed that the acute toxicity of Vulcuren (purity: 86.3) is very low. The oral LD 50 value is above 2000 mg/kg body weight and the dermal LD50 value is also above 2000 mg/kg body weight.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.