Registration Dossier

Administrative data

Description of key information

Oral LD50 > 500 mg/kg bw and < 2000 mg/kg bw

Dermal LD50>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
Study period:
02 Nov 2016 to 08 Dec 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 30, 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Version / remarks:
November 24, 2000
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: BASF SE
- Lot/batch No. of test material: Ra-He 2014-054
- Expiration date of the lot/batch: October, 2017
- Purity test date: 100% UVCB
- Appearance: solid / beige

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: between 170 - 180 g
- Fasting period before study: 16 hours
- Housing: caged individually in Makrolon cage, type III
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Enrichment: Wooden gnawing blocks (Type 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
- Air changes (per hr): Approx. 10
- Photoperiod: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.5, 2.5 and 10 g/100 mL
- Amount of vehicle: 20 mL/kg bw
- Justification for choice of vehicle: Aqueous preparation corresponds to the physiological medium.

DOSAGE PREPARATION
The test item preparation for each test group was produced shortly before administration by stirring with a magnetic stirrer. The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.

TEST GROUPS
- Test group 1: 2000 mg/kg bw in 1 administration
- Test group 2: 500 mg/kg bw in 1 administration
- Test group 3: 500 mg/kg bw in 2 administrations
Doses:
500 and 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Observation period: 14 days
- Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter, on the last day of observation and on the day of death starting with study day 1.
- Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
- Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived
- Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
- Histology: No histological examinations were performed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- All animals of the single 2000 mg/kg bw test group died on study day 1 after administration.
- No mortality occurred in both 500 mg/kg bw test groups.
Clinical signs:
- Clinical signs in the single 2000 mg/kg test group revealed in all animals impaired general state and piloerection at hour 5 or from hour 4 until hour 5 after administration, while dyspnea and cowering position were seen at hour 5. All animals were found dead on day 1.
- Clinical signs in the first 500 mg/kg bw test group were in all animals impaired general state and piloerection from hour 2 until hour 5 or day 1 after administration.
- Clinical signs in the second 500 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 3 until hour 5 after administration, while one of these animals additionally showed dyspnea from hour 3 until hour 5.
Body weight:
The body weights of all surviving animals increased throughout the study period within the normal range.
Gross pathology:
- The following macroscopic pathologic findings were observed in the animals that died in the 2000 mg/kg bw test group (3 females): strong filled stomach, mustard discolored contents, strong red discoloration of the glandular stomach, strong red discoloration of the small intestine, congestion of the kidneys.
- There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (both 500 mg/kg bw. groups, 6 females).
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
500 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:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg
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: Charles River Wiga GmbH, Germany
- Age at study initiation: males approx. 8 weeks, females approx. 12 weeks
- Weight at study initiation: mean males 231.2 g, mean females 203.0 g
- Housing: single housing, in Makrolon type III cages; H15005-29 bedding, Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany); NGM E-022 enrichment, ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before the experimental phase
- Females were nulliparous and non-pregnant

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:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10
- Type of wrap if used: semi-occlusive 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: after removal of the semi-occlusive dressing, the application site was rinsed with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.4 mL/kg bw was applied to the clipped epidermis (dorsal and dorsolateral parts of the trunk)
Duration of exposure:
24 hours
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 for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Scoring of the skin finding: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
The body weight of the male animals increased within the normal range throughout the study period. The female animals showed stagnation of body weight in two animals, while in the other three animals a marginal loss of body weight was observed during the first week. Two female animals gained weight in a normal range during the second week, while the other three animals showed stagnation of body weight during the second week. Due to the fact, that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.
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:
Four female animals showed well-defined erythema (grade 2) from day 1 until day 2 or 8 after application, which decreased in three of these animals to very slight erythema (grade 1) from day 5 or 12 until day 8 or 14. In the fourth animal well-defined erythema regressed to very slight erythema (grade 1) on day 5, but progressed again to well-defined erythema on day 8, followed by very slight erythema from day 12 until day 14. In the fifth animal, very slight erythema was seen on day 1, only. Very slight edema (grade 1) was noted in four animals from day 1 until day 2. Scaling was noted in three animals on day 5 and persisted in one of these animals until day 6. Additionally, incrustations were noted in three animals from day 8 or 12 until day 14.
Eczema like skin lesions were seen in one animal from day 5 until day 8, while weeping areas of the skin were noted in two other animals on day 1 after application only.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

In an Acute Toxic Class Method study performed according to OECD 423 under GLP conditions, the acute oral toxicity to rats was assessed (Bioassay, 2017). A group of three fasted female Wistar rats were exposed to the test substance at a dose of 2000 mg/kg bw by gavage in one administration as a first step. In the second step, two groups of three fasted female Wistar rats were exposed to the test substance at a dose of 500 mg/kg bw. The first group received the dose in one administration, the second in two administrations. After an observation period of 14 days animals were necropsied. In the 2000 mg/kg bw group, the following clinical signs were recorded: mortality in all animals, impaired general state in all animals, dyspnoea in all animals, piloerection in all animals and cowering position in all animals. In the two 500 mg/kg bw groups, no mortality occured. The following clinical signs were recorded: impaired general state in all animals, piloerection in all animals and dyspnea in one animal. Body weigths were normal and no macroscopic pathological findings were observed in the surviving animals. The LD50 was determined to be >500 mg/kg bw and < 2000 mg/kg bw.

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 2000 mg/kg bw of Fatty acids, C12-14, a-sulfo, disodium salts (as suspension in deionized water) (Bioassay, 2017). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

Neither mortality nor signs of systemic toxicity were observed in the animals.

The following test item-related local effects were recorded during the course of the study, local effects occurred within 14 days after application:

 Very slight to well-defined erythema (grade 1 to 2)

 Very slight edema (grade 1)

 Incrustations

 Scaling

 Eczema like skin lesions

 Weeping areas of the skin

 No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study.

The body weight of the male animals increased within the normal range throughout the study period. The female animals showed stagnation of body weight in two animals, while in the other three animals a marginal loss of body weight was observed during the first week. Two female animals gained weight in a normal range during the second week, while the other three animals showed stagnation of body weight during the second week. Due to the fact, that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.

No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw

Justification for classification or non-classification

Based on the available data, the substance has to be classified as Acute Tox. 4; H302: 'Harmful if swallowed' according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008