Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

The LD50 for acute oral toxicity was determined to be > 2000 mg/kg bw and the LD50 for acute dermal toxicity was determined to be > 5000 mg/kg bw. Therefore, the test item is not considered to cause acute toxicity via oral or demal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1963
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
For assessment of the acute oral toxicity, Deriphat 160 -C (10% active ingredient in water), was administered by single gavage to rats, at dose levels of 15400, 23100, 34600 and 51900 mg/kg bw. Each test group comprised 2 male and 2 female animals. The testing method in principle was similar to the OECD TG 401.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not specified
- Weight at study initiation: approx. 130 g
- Fasting period before study: 16 hours (food withdraw)
- Housing: individually in stock cages
- Diet: Standard laboratory rat diet (Rockland Rat Diet, Rockland Farms, New City, New York), ad libitum
- Water: ad libitum
- Acclimation period: 5 days
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
15400, 23100, 34600 and 51900 mg/kg bw (calculated doses of the undiluted test material)
No. of animals per sex per dose:
2/sex/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: particular attention was given to observation for mortalities and clinical symptoms during the first 4 hours following treatment.
Statistics:
The LD50 was calculated using the techniques of Weil CS (Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8: 249-263, 1952), Thompson WR (Use of moving averages and interpolation to estimate median-effective dose. Bact Rev Nov 1947), and Thompson & Weil (On the construction of tables for moving average interpolation. Biometrics, March 1952).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
31 300 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 130 mg/kg bw
Based on:
act. ingr.
Mortality:
- 100% (4/4) mortality was observed at 51900 mg/kg bw;
- 50% (2/4) mortality was observed at 34600 mg/kg bw;
- 25% (1/4) mortality was observed at 23100 mg/kg bw;
- no mortality occurred at 15400 mg/kg bw.
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
PRODUCT IDENTIFICATION: sodium N-(2-carboxyethyl)-N-dodecyl-β-alaninate, 16% Solids, pH 7.0, #54R-74
PRODUCT DESCRIPTION: Clear yellow liquid.
PSL NO.: E20506-2
PRODUCT IDENTIFICATION: Mirataine H2C-HA
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Royalhart Colony
- Weight at study initiation: 20-35g
- Fasting period before study: 18h prior
- Housing: housed in stainless steel wire bottomed cages in an environmentally controlled room
- Diet and water: ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 22.2°C
- Photoperiod: 12h dark / 12h light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.66 mL
Doses:
10, 15 and 20 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: signs of gross toxicity
Statistics:
common statistics
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
17.8 mL/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
2.85 mL/kg bw
Based on:
act. ingr.
Mortality:
20 mL/kg bw - Morality male 5/5, female 4/5
15 mL/kg bw - Morality male 0/5, female 0/5
10 mL/kg bw - Morality male 0/5, female 0/5
Clinical signs:
No clinical signs observed.
Body weight:
No effects observed.
Gross pathology:
No effects observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 130 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): DERIPHAT 160 C
- Physical state:Solid, white
- Analytical purity: 97% The test substance was characterized analytically (for details see the analytical report; project no.: AU 122958-1)
- Lot/batch No.:4986V1
- Expiration date of the lot/batch: until 03 Jun 2014
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system 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. 12 weeks
- Weight at study initiation:203-236g
- Housing:Makrolon cage, type III
- Diet & water: ad libitum
- Acclimation period: At least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light):12 / 12
Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure:40 cm²
- % coverage: at least 10% of the body surface
- Type of wrap if used: semi-occlusive dressing

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: suspension in olive oil

VEHICLE (olive oil)
- Amount(s) applied (volume or weight with unit): 20 mL/kg bw (substance in vehicle)
- Concentration (if solution): 25 g/100 mL (concentration of substance in olive oil)
Duration of exposure:
24h
Doses:
5000 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
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: Recording of clinical signs 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) and several times (see results) until the last day of observation
- Mortality: Check for any dead or moribund animals at least once each workday
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period
Statistics:
common statistics
Key result
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination
Body weight:
The mean body weight of the:
- male animals increased throughout the study period within the normal range.
- female animals did not change significantly, during the first post-exposure observation week. The reason is that female animals have already reached the phase of slow growth when they are used for the experiment at the required age 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:
Skin effects:
Very slight erythema (grade 1) at the application site was observed in all male animals, during study day 1 and 2.
Very slight erythema (grade 1) at the application site was observed in four out of five female animals during study day 1 until day 2
One female animal revealed very slight erythema (grade 1) during study day 1 and day 2, well-defined erythema (grade 2) during study day 2 and day 3 and scaling on day 6.
Scaling was observed in 2 more female animals, of which one also revealed incrustations,during study day 6.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

Acute toxicity via the oral route:

The assessment of the acute toxicity via the oral route for the test substance is based on 2 study records used in a Weight of Evidence approach. In the first study record, for assessment of the acute oral toxicity the test item (10% active ingredient in water), was administered by single gavage to rats, at dose levels of 15400, 23100, 34600 and 51900 mg/kg bw (IBT,1963). Each test group comprised 2 male and 2 female animals. The testing method in principle was similar to the OECD TG 401. 100% (4/4) mortality was observed at 51900 mg/kg bw, 50% (2/4) mortality was observed at 34600 mg/kg bw and 25% (1/4) mortality was observed at 23100 mg/kg bw, whereas no mortality occurred at 15400 mg/kg bw dose group. Hence the LD50 was set to 31300 mg/kg bw. Taking the dilution factor into account the LD50 was found to be 3130 mg/kg bw (calculated for active ingredient). In the other study record the test item (16% active ingredient), was administered by single gavage to mice at dose levels of 10, 15 and 20 ml/kg bw (PSL, 1982). Each test group comprised 5 male and 5 female animals. The testing method in principle was similar to the OECD guideline 401. The following mortality was observed: At the dose of 20 mL/kg bw, 5/5 males and 4/5 females died. At the dose of 15 mL/kg bw and at the dose of 10 mL/kg bw no mortality was observed. The LD50 was calculated as 17.8 mL/kg bw. Taking the dilution factor into account the LD50 was found to be 2.85 mL/kg bw.

 

Acute toxicity via the dermal route:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the test substance (as suspension inolive oil Ph.Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours according to OECD 402. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. The following test item-related local effects were recorded during the course of the study: Very slight to well-defined erythema (grade 1 to 2), very slight edema (grade 1), incrustations and scaling. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals did not significantly change during the first post-exposure observation week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. No signs of systemic toxicity or mortality were observed in the animals. 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 > 5000 mg/kg bw (BASF, 2013).

 

For assessment of the acute dermal toxicity the test item was applied onto the clipped dorsal skin of rabbits, under occlusive conditions, for 24 hours. The test conduct was in principle similar to the OECD TG 402. The tested dose levels were 6800 and 10200 mg/kg bw. After removal of the dressing, the animals were observed over a period of 14 days. Since neither mortality nor clinical symptoms of toxicity were observed, the LD0 was set at 10200 mg/kg bw; no LD50 was derived. Taking the dilution factor into account the LD0 was found to be 1020 mg/kg bw (calculated for active ingredient) (IBT, 1963).

 

Justification for classification or non-classification

Based on the available information classification for acute oral and dermal toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.