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Description of key information

oral LD50 (male/female) > 2000 mg/kg bw (reference 7.2.1 -1)

dermal LD50 (male/female) > 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:
1990-03-13 to 1990-03-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
version 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Chbb: THOM
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 7 to 9 weeks
- Weight at study initiation: 183 (174 - 193) g
- Fasting period before study: ca. 17 h before and 4 h after treatment
- Housing: 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): 24 to 27
- Humidity (%):38 to 46
- Air changes (per hr): not detailed, but room air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 13.03.1990 - 27.03.1990
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.1 g/mL

MAXIMUM DOSE VOLUME APPLIED:
20 mL/kg bw for 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 per sex
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:
The body weight data were processed by means of the program TOX 511 A, developed by the Department of Technical and Scientific Data Processing of E. Merck, Darmstad.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All the rats survived the observation period.
Clinical signs:
No intoxication symptoms were seen.
Body weight:
Body weight development of treated and control rats was normal.
Gross pathology:
In the rats which were all sacrificed at the end of the observation period no organ alterations were seen.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of this study, it is concluded, that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw following oral treatment in rats.
Executive summary:

In an acute oral toxicity study according to OECD 401, groups (5/sex) of Wistar Chbb: THOM rats, were given a single oral dose of the test item in methylcellulose at doses of 2000 mg/kg bw per gavage and observed for 15 days. The limit test with 2000 mg/kg showed no mortality. Body weight development of treated and control rats was normal. No abnormalities were detected during gross pathological examinations. For both sexes the LD50 was therefore determined to be > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 401, GLP

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:
19.09.1990 to 03.10.1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Chbb:THOM
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae, Biberach
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 7 to 9 weeks
- Weight at study initiation: 204 (188 - 220) g
- Fasting period before study: none
- Housing: Makrolon cages type III
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 to 31
- Humidity (%):40 to 56
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 19.09.1990 to 03.10.1990
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The backs and abdomens of the rats were shaved with an electric hair clipper approximately one hour before treatment. The test material preparation was applied to the shaven, unscarified skin in an area of 6 x 6 cm and covered with tin foil which was kept in place and sealed by a rubber sleeve (modified method of NOAKES and SANDERSON, 1969*). The time of occlusive exposure was 24 hours. Then rubber sleeve and tin foil were removed and any remaining test material was wiped off carefully.


Prior to application 4.4 g test item were moistened with 4.4 g aqua pro injectione. From this preparation 4000 mg/kg corresponding to a dose of 2000 mg test item/kg body weight were administered to each rat. The control rats from another study were treated with 20 mL/kg of 0.25 % aqueous solution.
Duration of exposure:
24 h
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: clinical signs: at least 6 hours after administration and then checked 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, mortality
Statistics:
The body weight data were processed by means of the program TOX 511 A, developed by the Department of Technical and Scientific Data Processing of E. Merck, Darmstadt.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All the rats survived the observation period.
Clinical signs:
After removal of the rubber sleeve seven of ten rats showed pale eyes on day 2 of the study. No local symptoms were observed.
Body weight:
Body weight development of treated and control rats was normal.
Gross pathology:
In the rats which were all sacrificed at the end of the observation period no organ alterations were seen.
Other findings:
None.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, test substance can be considered to have no acute dermal toxic potential and the expected LD50 value is higher than 2000 mg/kg bw after dermal administration to rats.
Executive summary:

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw according to OECD Guideline 402 under GLP conditions. There were no deaths during the course of the study, so the lethal dose is expected to be higher than the limit dose tested. The body weight development was inconspicuous and the gross pathological examination revealed no organ alterations. Based on the results of this study, test substance can be considered to have no acute toxic potential and the expected LD50 value is higher than 2000 mg/kg bw after dermal administration to rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 402, GLP

Additional information

Acute oral toxicity study

In an acute oral toxicity study, one group of fasted, young adult Wistar rats (3/sex) were given a single oral dose of the test item prepared with aqueous Methocel® K4M Premium solution (2.5 g/L) as vehicle at a dose of 2000 mg/kg bw and observed for 14 days.

The oral LD50 value was determined to be:

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

No mortality occurred in this limit test.

There were no treatment related clinical signs, necropsy findings or changes in body weight (reference 7.2.1 -1).

Acute dermal toxicity study

In an acute dermal toxicity study, one group of young adult Wistar rats (5 /sex) were dermally exposed to the test item in water for 24 hours to the shaven body surface area of 6 x 6 cm of at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

The dermal LD50 value was determined to be:

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

No mortality occurred in this limit test.

No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg. No deaths occurred during the course of the study. There were no treatment related clinical signs, necropsy findings or changes in body weight (reference 7.2.3 -1).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on actue toxicity, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.