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Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw (male and female rats)

Dermal Rat: LD50 > 2000 mg/kg bw (rat, semiocclusive)

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:
9 March 1993 to 30 December 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
19 September 1984
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Acute Toxic Class Method (ATC Method) by E. Schlede, U. Mischke, R. Roll, D. Kayser: A National Validation Study of the Acute-Toxic-Class Method - An Alternative to the LD50 Test. Arch. Toxicol. 66: 455-470 (1992).
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: P. 28/93

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, exclusion from light
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, 7950 Biberach
- Age at study initiation: not spezified (young adult animals)
- Weight at study initiation: mean body weigt of three male animals: 183 g; mean body weight of three female animals: 180 g
- Fasting period before study: no feed at least 16 hrs before administration, but water was available ad libitum
- Housing: single housing
- Diet: Kliba diet 343, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 March 1993 To: 25 March 1993
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 400 mg/mL
- Amount of vehicle: 5 mL/kg bw
- Justification for choice of vehicle: test substance is insoluble in aqua bidest

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
-Duration of observation period following administration: 14 days
-Frequency of observation and weighing: animals were checked for mortality twice each workday and once on saturday, sunday and on public holidays for general observations and for any dead or moribund animals. Weighing was performed before application (day 0), weekly thereafter and at the end of the study. Recording of toxicological signs and symptons several times on the day of administration, at least once each workday for the individual animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and symptoms, body weight, general observations and mortality, pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No abnormalities were observed.
Body weight:
Body weight gain during study meets expectations.
Gross pathology:
Necropsy at the end of the study revealed no abnormalities.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP study according to OECD guideline.

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:
07 September 2011 to 18 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Batch identification: 110007P040
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: males: 8 weeks, females: 12 weeks
- Weight at study initiation: 212 ± 7.05g (males); 218.4 ± 4.39 g (females)
- Fasting period before study: no
- Housing: single in Makrolon type III cages
- Diet: VRF1(P); SDS Special diets services, Altrip, Germany, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12h / 12h
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (correspond to at least 10 % of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze and stretch bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24h (directly after removal of the semiocclusive dressing)

TEST MATERIAL
- Amount applied: 1.89 mL/kg bw
- Concentration: undiluted
- Constant volume or concentration used: yes


Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
> clinical signs: several times during exposure, daily thereafter,
> body weight: day 0, weekly thereafter and on the last day of observation,
> skin findings: 30-60 min after removal of the dressing, weekly thereafter according to Draize
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.

local irritation (erythema up to grade 3, edema up to grade 1) were observed up to day 6 in males and up to day 10 in females. Scaling and incrustations were also observed in 1 and 2 females, respectively.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
- Local effects:
In one female animal well-defined erythema (grade 2) was observed from study day 1 until study day 3. In two females moderate erythema (grade 3) was noted from study day 1 until study day 3. In one of these two animals moderate erythema decreased to very slight erythema (grade 1) on study day 6. In the other animal moderate erythema decreased step-wise from well-defined (study day 6) to very slight erythema (study days 7 and 8).
Furthermore following findings were observed in this animal: very slight edema (grade 1) from study day 1 until study day 3, scaling on study day 6 and 7, findings beyond the application area from study day 2 until study day 7 and incrustations from study day 6 until study day 9.
In two further animals well-defined erythema (grade 2) was noticed on study day 1, but increased to moderate erythema (grade 3) and was observed on study day 2 and 3. This grade decreased step-wise: well-defined erythema was observed on study day 6, while very slight erythema was noticed on study day 7. In one of these two animals incrustations were observed from study day 6 until study day 8. All local effects were reversible until day 10 at the latest.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP study according to OECD guideline.

Additional information

Acute oral toxicity

A study was performed to assess the range of mortality following oral administration of the test material, applied as an emulsion in olive oil, to Wistar rats (BASF AG, 1994). The study procedure was based on the EEC guideline and modified according to the acute toxic class method. A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of test material preparation in olive oil dab 10 at a dose level of 2000 mg/kg body weight. Signs of toxicity have not been noted. The expected body weight gain has generally been observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of the animals sacrificed at the end of the study. Under the conditions of this study the range of mortality after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

 

In a second acute toxicity study according to OECD 401 (BASF AG, 1995), 5 male and 5 female Wistar rats were exposed to a single dose of 5000 mg/kg bw test substance in CMC via gavage. The animals were observed for 14 days and showed the expected body weight gain and no clinical signs throughout this period. No mortalities occurred and the necropsy at the end of the study revealed no abnormalities.

 

Acute dermal toxicity

In an acute dermal toxicity study (BASF SE, 2011), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

No mortality occurred. No signs of systemic toxicity were observed in the animals. The following test item-related local effects were recorded during the course of the study:

- Very slight to moderate erythema (grade 1 to 3)

- Very slight edema (grade 1)

- Incrustations (in two females)

- Scaling (in one female)

- Findings beyond the application area (in one female)

- All local effects were reversible until day 6 (males) or day 10 (females) at the latest

The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study Accordingly, the acute dermal median lethal dose (LD50) was determined to beLD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.