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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September - November 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Phosphoric acid, mono C16-20 (branched, even numbered) alkyl esters
Molecular formula:
unspecified
IUPAC Name:
Phosphoric acid, mono C16-20 (branched, even numbered) alkyl esters
Test material form:
liquid: viscous
Details on test material:
- Name as cited in the report: SAT150011
- Chemical name: Phosphoric acid, mono C16-20 (branched, even numbered) alkyl esters
- Batch No.: RP GW 915 MU
- Storage Conditions: room temperature
- Expiration date: March/April 2016
- Description: clear, light amber, viscous liquid
- Molecular weight: approx. 340 Da
- Purity: 73.8 % Mono- and Diester (NMR)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
ANIMALS

Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 per step
Age at the beginning of the study: 7-9 weeks old
Body weight on the day of administration: step 1: 148 -150 g; step 2: 147 -150 g

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

HOUSING & FEEDING

- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0631)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102150820)
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least four to five days) under laboratory conditions

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
< 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off
Mortality:
None.
Clinical signs:
other: The test item showed acute oral toxicity characteristics after a single dose administration (reduced spontaneous activity, prone position, slow movement, wasp waist, piloerection and eyes half closed).
Gross pathology:
No specific gross pathological changes were recorded for any animal.

Any other information on results incl. tables

CLINICAL SIGNS PER STEP

STEP 1: 2000 mg/kg bw, 3 females

 0 minutes  none
 60 minutes  Spontaneous activity slightly reduced, piloerection (slight), eyes half closed
 2 d - 15 d  none

STEP 2: 2000 mg/kg bw, 3 females

 0 minutes  none
 60 minutes  Spontaneous activity slightly reduced, slow movements, Piloerection (moderate), eyes half closed
 2 d - 15 d  none

PATHOLOGY

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

LD50 CUT-OFF

 starting dose [mg/kg bw]  no. of animals  no. of intercurrent deaths  LD50 cut-off
 2000  6  0  5000 mg/kg bw

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral application of the test item SAT150011 to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of SAT150011 after a single oral administration to female rats, observed over aperiod of 14 days is:
LD50 cut-off (rat): 5000 mg/kg bw
According to Annex I of Regulation (EC) 1272/2008 the test item SAT150011 has no obligatory labelling requirement for toxicity and is not classified.
According to GHS (Globally Harmonized Classification System) the test item SAT150011 has obligatory labelling requirement for toxicity and is classified into Category 5.
Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved in the vehicle corn oil at a concentration of 2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study were allowed to acclimatise to the laboratory conditions for at least 4-5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs, All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

- Step 1: 3 females, starting dose 2000 mg/kg bw, number of intercurrent deaths: 0

- Step 2: 3 females, starting dose 2000 mg/kg bw, number of intercurrent deaths: 0

All animals survived until the end of the study showing signs of toxicity. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, prone position, slow movement, wasp waist, piloerection and eyes half closed . All symptoms recovered within 1 day post-dose.

Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain.

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

On the basis of the test results given below and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be: not classified.

On the basis of the test results given below and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be: classified into category 5.

- LD50 cut-off: 5000 mg/kg bw

- Species/strain: WISTAR Crl: WI(Han) rats

- Vehicle: corn oil

- Number of animals: 3 per step 1 2 steps performed

- Method: OECD 423, EC 440/2008, Method 8 .1 tris, OPPTS 870.1100