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Administrative data

Description of key information

Oral (OECD TG 401), rat: LD50 between 1000 and 2000 mg/kg bw (reference 7.2.1 -1)

Dermal (OECD TG 402), rat: LD50 > 2000 mg/kg bw (reference 7.2.3 -1).

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:
1996-08-01 to 1996-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
29 December 1992
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Remarks:
HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 6 to 9 weeks
- Weight at study initiation: 152 - 202 g (mean: 177 g)
- Fasting period before study: ca. 17 h before and 4 h after treatment
- Housing: single, Makrolon cages type III
- Diet: ad libitum, besides fasting period
- Water: ad libitum, besides fasting period, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 41 - 77
- Air changes (per hr): not detailed, but room air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 08.08.1996 - 29.08.1996
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
1.697 mL/kg bw for 2000 mg/kg bw
0.849 mL/kg bw for 2000 mg/kg bw
Doses:
1000 and 2000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 per sex
1000 mg/kg bw: 5 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observation: daily; body weight: on days 2, 4, 6, 8,11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
For body weights the group mean value and the difference to the first value, expressed as percentage, were calculated for each measurement.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 3 Deaths occured up to day 3 after treatment.
Male: 1000 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:
1000 mg/kg: locomotor disturbance started between 15 to 60 minutes after treatment and lasted on day 1.
2000 mg/kg: Symptoms of intoxication were first seen 1 to 15 minutes after treatment. They lasted up to day 3 and consisted of locomtor disturbance, dyspnea, retention of feces, blood crusted snout, salivation, and abdominal position.
Body weight:
Body weight development was impaired on day 2 for females and on day 2 and 4 for males treated with 2000 mg/kg bw. Afterwards bodyweight gain was observed.
Males treated with 1000 mg/kg bw showed body weight gain on all days.
Gross pathology:
The rats that died or were sacrificed at the end of the observation period did not show any abnormalities in the macroscopic examination.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
For both sexes the combined LD50 was therefore determined to be >1000 to < 2000 mg/kg bw.
Executive summary:

An in vivo oral toxicity study according to OECD 401 using the test substance was conducted in rats. Each 5 male and female animals were treated with 2000 mg/kg bw test substance per gavage and observed for 15 days. Furthermore, 5 males were treated with 1000 mg/kg bw test substance. In animals treated with 2000 mg/kg bw symptoms of intoxication were first seen 1 to 15 minutes after treatment. They lasted up to day 3 and consisted of locomotor disturbance, dyspnea, retention of feces, blood crusted snout, salivation, and abdominal position. After treatment with 1000 mg/kg bw locomotor disturbance developed after 15-60 minutes and lasted up to one day. Three male rats from the high dose group died up to day 3 of the study. Body weight development was impaired on day 2 for females and on day 2 and 4 for males treated with 2000 mg/kg bw. Afterwards bodyweight gain was observed. Males treated with 1000 mg/kg bw showed body weight gain on all days.No abnormalities were detected during gross pathological examinations. Based on the observed mortality the LD50 for male rats was determined to be below 2000 mg/kg bw but greater than 1000 mg/kg bw. For females the observed LD 50 was greater than 2000 mg/kg bw. For both sexes the combined LD50 was therefore determined to be >1000 to < 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw

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:
2000-01-25 to 2000-02-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
29 Decembre 1992
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 7 to 10 weeks
- Weight at study initiation: 217 g (range from 202 to 240 g)
- Housing: separately in Makrolon cages type III
- Diet: ad libitum, diet (Altromin Standard Diät TPF®N 1324)
- Water: ad libitum, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 38 - 66
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs and abdomens, area of 6 x 6 cm
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 1.7 mL/kg
Duration of exposure:
24 h
Doses:
2000 mg/kg
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: daily, weighing was performed on days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The body weight data were recorded with the PC-program „AKUDAT". The statistical evaluations of the body weight were carried out with the PC-program „TOX 511 A", developed by the Institute of Toxicology of Merck KGaA, Darmstadt. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement.
Key result
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
All the rats survived the observation period.
Clinical signs:
No signs of intoxication and no signs of local irritation occurred after treatment.
Body weight:
An inhibition of body weight, released from the tape, was observed on day two of the experimental part. Later on the body weight development of the treated rats was inconspicuous.
Gross pathology:
All rats which were sacrificed at the end of the study showed no macroscopic abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, the test item has no acute toxic potential and the LD50 value is higher than 2000 mg/kg bw after single dermal administration to male and female rats.
Executive summary:

The test substance was tested for acute toxicity in rats after dermal administration of 2000 mg/kg body weight in accordance with OECD guideline 402. Groups of Wistar rats (5/sex) were dermally exposed to the test substance for 24 hours. The test material was a liquid and was spread on the shaven skin in an area of 6 x 6 cm covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The gauze and adhesive fabric were removed after exposure time and any remaining test material was wiped off carefully. Animals were then observed for 14 days.

No signs of toxicity were detected in the rats after treatment with 2000 mg/kg. Weight development was not affected by the treatment. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

Based on the result of this study, the test substance can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

An in vivo oral toxicity study according to OECD 401 using the test substance was conducted in rats. Each 5 male and female animals were treated with 2000 mg/kg bw test substance per gavage and observed for 15 days. Furthermore, 5 males were treated with 1000 mg/kg bw test substance. In animals treated with 2000 mg/kg bw symptoms of intoxication were first seen 1 to 15 minutes after treatment. They lasted up to day 3 and consisted of locomotor disturbance, dyspnea, retention of feces, blood crusted snout, salivation, and abdominal position. After treatment with 1000 mg/kg bw locomotor disturbance developed after 15-60 minutes and lasted up to one day. Three male rats from the high dose group died up to day 3 of the study. Body weight development was impaired on day 2 for females and on day 2 and 4 for males treated with 2000 mg/kg bw. Afterwards bodyweight gain was observed. Males treated with 1000 mg/kg bw showed body weight gain on all days. No abnormalities were detected during gross pathological examinations. Based on the observed mortality the LD50 for male rats was determined to be below 2000 mg/kg bw but greater than 1000 mg/kg bw.For females the observed LD 50 was greater than 2000 mg/kg bw. For both sexes the combined LD50 was therefore determined to be >1000 to < 2000 mg/kg bw.

Acute dermal toxicity

The test substance was tested for acute toxicity in rats after dermal administration of 2000 mg/kg body weight in accordance with OECD guideline 402. Groups of Wistar rats (5/sex) were dermally exposed to the test substance for 24 hours. The test material was a liquid and was spread on the shaven skin in an area of 6 x 6 cm covered with a gauze patch. This was kept in place by a self-adhesive fabric (Fixomull® stretch, Beiersdorf). The gauze and adhesive fabric were removed after exposure time and any remaining test material was wiped off carefully. Animals were then observed for 14 days.

No signs of toxicity were detected in the rats after treatment with 2000 mg/kg. Weight development was not affected by the treatment. There were no deaths during the course of the study. The gross pathological examination revealed no organ alterations.

Based on the result of this study, the test substance can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Justification for classification or non-classification

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute oral toxicity cat. 4 (Harmful if swallowed) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521. No claasification is needed for acute dermal toxicity.