Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 2018 - October 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Sulfuric acid, mono-C8-18-alkyl esters, magnesium salts, compds. with triethanolamine
EC Number:
287-840-3
EC Name:
Sulfuric acid, mono-C8-18-alkyl esters, magnesium salts, compds. with triethanolamine
Cas Number:
85586-38-5
IUPAC Name:
85586-38-5
Test material form:
solid
Remarks:
dried from of a reaction mixture, water and cyclohexanol where evaporated
Details on test material:
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: February 2020
Storage conditions: Room temperature
pH-value: Approx. 7 (moistened with water, determined by Bioassay Laboratories)
Specific details on test material used for the study:
For details see analytical report 18L00152
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: February 2020
Storage conditions: Room temperature
Physical state/ color: Solid / white

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 175-182g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing:
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing

- Diet (e.g. ad libitum): R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany), ad libitum
- Water (e.g. ad libitum):Tap water ad libitum
- Acclimation period:Acclimatization period of at least 5 days before the beginning of the experimental phase
- Microbiological status when known: SPF
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): Approx. 10
- 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.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
preparations in deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20g/100ml
- Amount of vehicle (if gavage): total admin volume 10ml/kg
- Justification for choice of vehicle:solubility

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg Testitem



CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
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 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 by Bioassay.
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.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the first 2000 mg/kg test group.
One animal of the second 2000 mg/kg test group was found dead on day 1 after administration.
Clinical signs:
other: Clinical signs in the first 2000 mg/kg test group revealed in all animals impaired general state and piloerection from hour 1 or 2 until study day 3 after administration, respectively. Cowering position was seen in all animals from hour 2 until hour 4, wh
Gross pathology:
The following macroscopic pathologic findings were observed in the single animal that died in the second 2000 mg/kg bw test group:
o Dark discoloration of liver and lung lobes
o Gasified stomach with liquid contents
o Advanced putrefaction. There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (5 females).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of Component in "Confidentail Name" after oral administration was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method (OECD 423), a dose of 2000 mg/kg bw of the test item Component in "confidential substance name" (preparations in deionized water) were administered by gavage to two test groups of three fasted Wistar rats each (6 females) (BASF SE 2019).
The following test substance-related clinical observations were recorded, clinical signs occurred within the first 3 days after administration:
2000 mg/kg (first test group):
 No mortality occurred
 Impaired general state in all animals
 Piloerection in all animals
 Reduced defecation in one animal
 Cowering position in all animals
2000 mg/kg (second test group):
 Mortality in one animal
 Piloerection in all animals
 Impaired general state in all animals
 Cowering position in two animals
 Dyspnoea in two animals
 Respiratory noises in one animal
 Macroscopic pathological findings in the single animal that died:
o Dark discoloration of liver and lung lobes
o Gasified stomach with liquid contents
o Advanced putrefaction
The body weights of the surviving animals (5 females) increased within the normal range throughout the study period.
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (5 females).
The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw