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Administrative data

Description of key information

In the acute oral toxicity study, the LD50 value was greater than 5010 mg/kg bw.
And in the acute dermal toxicity study, the LD50 value was greater than 2000 mg/kg bw.

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
1 and 10% in aqueous solution
Doses:
20, 79, 316, 1260 and 5010 mg/kg bw
No. of animals per sex per dose:
high dose: 10 animals
lower doses: 1 animal
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: after 1 hour, 24 hours, 48 hours, 3 days and 7 days.
- Necropsy of survivors performed: yes
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 010 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
No effects were reported.
Gross pathology:
Blood congestion in the liver and spleen in 4 animals at the high dose.
Interpretation of results:
GHS criteria not met
Conclusions:
In the acute oral toxicity study in rats, the LD50 value was greater than 5010 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
In accordance with column 2 of REACH Annex VIII-X, in addition to the oral route, for substances other than gases, an acute toxicity study for at least one other route is required. The choice of the second route will depend on the nature of the substance and the likely route of human exposure. As dermal is the most likely route of exposure and acute dermal toxicity data is available, no data gap exists.
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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay Labor für biologische Analytik GmbH
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 11-0041
- Test substance No.: 08/0054-4

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: male animals approx. 8 weeks; female animals approx. 10 weeks.
- Weight at study initiation: Males: 225-259 g; Females: 201-219 g (both males and females ± 20% of the mean weight)
- Housing: single housing in Makrolon cage, type III. Fully air-conditioned rooms. Bedding: H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany). Enrichment: NGM E-022; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany) ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Deionized
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm²
- % coverage: At least 10% of the body surface
- Type of wrap: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL / VEHICLE
- Amount(s) applied: 4 mL/kg bw
- Concentration: 50 g/100 mL
Duration of exposure:
24 hours
Doses:
A single exposure of 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Test item preparation: The test item preparation was produced for the application group shortly before application by stirring with a magnetic stirrer. Additionally the homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer.

ANALYSIS
- Conduct of analyses: Samples of the test-item formulation were sent to the sponsor for analysis (BASF SE, Z470, 67056 Ludwigshafen, Germany).
- Stability of the test item preparation: The stability of the test item in the vehicle will determined indirectly by concentration control analysis. For this purpose, the samples taken were stored at room temperature over the maximum duration of the administration period, subsequently deep-frozen and sent to the sponsor for analysis.
- Homogeneity of the test item preparation: The homogeneity of the test item preparation will be determined indirectly by concentration control analysis.
- Concentration control analysis of the test item preparation: A concentration control analysis of the test item preparation and archiving of the respective data will be done by the sponsor.
- Analysis of feed: The feed used in the study was assayed for chemical and microbial contaminants by the manufacturer in quarterly intervals.
- Analysis of drinking water: The drinking water was regularly assayed for contaminants by the municipal authorities of Heidelberg. The German Drinking Water Regulation of Dec. 5, 1990 served as the guideline for maximum tolerable contaminants.
- Bedding and enrichment analysis: The bedding and enrichment were regularly assayed for contaminants (chlorinated hydrocarbons and heavy metals).

EXPERIMENTAL PROCEDURE
- Observation period: 14 days
- Body weight determination: shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.
- Assessment of skin reactions: The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.
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 local or systemic clinical signs were observed during clinical examination.
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.
Interpretation of results:
GHS criteria not met
Conclusions:
In the acute dermal toxicity study, an LD50 value greater than 2000 mg/kg bw in rats was determined.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral toxicity

In an acute oral toxicity study comparable to OECD guideline 401 (BASF, VIII/56, 1958), rats were exposed to dose levels of 20, 79, 316, 1260 and 5010 mg/kg bw of the substance by gavage and observed for 7 days. The highest dose was tested with 10 animals, the other doses were tested with 1 animal. No mortality and no clinical signs were observed. Gross pathology revealed blood congestion in the liver and spleen in 4 animals at the high dose. The LD50 was determined to be >5010 mg/kg bw.

 

Dermal toxicity

In a GLP acute dermal toxicity study (Limit Test), according to OECD 402 (Bioassay, 11-BF-DT109, 2012), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test substance (as suspension in deionized water) 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 or skin effects were observed in the animals. 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 be LD50, dermal, rat > 2000 mg/kg bw.

Inhalation toxicity

In accordance with column 2 of REACH Annex VIII-X, in addition to the oral route, for substances other than gases, an acute toxicity study for at least one other route is required. The choice of the second route will depend on the nature of the substance and the likely route of human exposure. As dermal is the most likely route of exposure and acute dermal toxicity data is available, no data gap exists.

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 acute toxicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP).