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Description of key information

The test item showed an acute oral LD50 greater than 2000 mg/kg bw  in the rat. The dermal LD50 for the test item was found to be greater than 2000 mg/kg bw in the rat. Performance of an inhalation toxicity study was waived, as exposure via inhalation is not considered relevant, due to unlikely exposure via inhalation.

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:
from 1994-11-16 to 1994-11-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study followed the procedures indicated by internationally accepted guidelines and recommendations as Commission Regulation (EC) No 440/2008 (B.1: Acute Toxicity (Oral)).
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
directive 92/69/EEC
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
24 February 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: BRL Ltd., Basel, Switzerland
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: males: mean 267 g; females: mean 181 g
- Fasting period before study: overnight prior to dosing
- Housing: polycarbonate cages, 5 animals per sex per cage
- Diet: standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days, under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50 % relative humidity
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
NA
Doses:
single dose: 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: mortality/viability: twice daily; clinical signs: once daily; body weights: day 1, 8, and 15;
- Necropsy of survivors performed: yes
Statistics:
NA
Preliminary study:
NA
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animals died during the study.
Clinical signs:
No clinical signs were observed during the study period.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
NA
Other findings:
Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities.

no remarks

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of the test item in rats was established as exceeding 2000 mg/kg body weight for both sexes.
Executive summary:

In an acute oral toxicity study, groups of fasted, approx. 10 weeks old Wistar rats (5/sex) were given a single oral dose of the test item in water at a dose of 2000 mg/kg bw and observed for 14 days.

No animals died during the study. No clinical signs were observed during the study period. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities.

The Oral LD50 was 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:
GLP and 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
Study period:
from 1994-08-11 to 1994-08-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study followed the procedures indicated by internationally accepted guidelines and recommendations as Commission Regulation (EC) No 440/2008 (B.3: Acute Toxicity (Dermal)).
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
directive 92/69/EEC
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 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: BRL Ltd., Basel, Switzerland
- Age at study initiation:approx. 8 weeks
- Weight at study initiation: males: mean 207 g; females: mean 175 g
- Fasting period before study: no
- Housing: polycarbonate cages, 5 animals per sex per cage
- Diet: standard pelleted laboratory animal diet (Kliba 343 from Klingentalmuhle AG, Kaiseraugst, Switzerland) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50 % rel. humidity
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day.

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm² (5 x 5 cm) for males and 18 cm² (3.5 x 5 cm) for females
- Type of wrap if used: aluminium foil and flexible bandage (Coban, 3M, St. Paul, U.S.A.)

REMOVAL OF TEST SUBSTANCE
- Washing: residual test substance was removed using a tissue moistened with tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg (1.869 mL/kg) body weight. Dose volume calculated as follows: dose level : specific gravity


Duration of exposure:
24 hours
Doses:
single dose: 2000 mg/kg b.w.
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: mortality/viability: twice daily; body weights on day 1, 8, and 15;
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: at periodic intervals on the day of the treatmen (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded.
Preliminary study:
NA
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of ill health or behavioural changes were observed during the study period. Abnormalites in the treated skin area included scabs in one male between days 5 and 9.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. However, three females showed low body weight gain over the second week of the study.
Other findings:
Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance.

no remarks

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of the test item in rats was established as exceeding 2000 mg/kg body weight.
Executive summary:

In an acute dermal toxicity study, groups of young adult (8 weeks old) Wistar rats (5/sex) were dermally exposed to the test item for 24 hours to (25 cm2 surface) at a limit doses 2000 mg/kg bw. Animals then were observed for 14 days.

No mortality occurred during the study period. No clinical signs of ill health or behavioural changes were observed during the study period. Abnormalites in the treated skin area included scabs in one male between days 5 and 9. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. However, three females showed low body weight gain over the second week of the study. Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance. The dermal LD50 value of the test item in rats was established as exceeding 2000 mg/kg body weight.

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

Additional information

In an acute oral toxicity study, groups of fasted, approx. 10 weeks old Wistar rats (5/sex) were given a single oral dose of the test item in water at a dose of 2000 mg/kg bw and observed for 14 days. No animals died during the study. No clinical signs were observed during the study period. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities. The Oral LD50 was determined to be > 2000 mg/kg bw.

In an acute dermal toxicity study, groups of young adult (8 weeks old) Wistar rats (5/sex) were dermally exposed to the test item for 24 hours to (25 cm2 surface) at a limit doses 2000 mg/kg bw. Animals then were observed for 14 days.

No mortality occurred during the study period. No clinical signs of ill health or behavioural changes were observed during the study period. Abnormalites in the treated skin area included scabs in one male between days 5 and 9. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. However, three females showed low body weight gain over the second week of the study. Macroscopic post mortem examination of the animals at termination revealed a yellowish hard nodule in the papillary process of the liver in one female and pelvic dilation of the kidney in one male. These findings are incidentally noted among the animals of this age and strain and are considered not related to treatment with the test substance. The dermal LD50 value of the test item in rats was established as exceeding 2000 mg/kg body weight.

Testing of inhalation toxicity of the test item was waived, as exposure via inhalation was not considered relevant.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Exposure via inhalation is not considered relevant, due to unlikely exposure via inhalation.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the results obtained from testing of the supporting substance, the test item was not classified and labeled according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).