Propanoic acid, 3-mercapto-, C11-14-isoalkyl esters, C13-rich

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-09-08 to 1998-10-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

; starting dose was not one of the four fixed levels given in the current guidelines

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

; starting dose was not one of the four fixed levels given in the current guidelines

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of iso-tridecyl 3-mercaptopropionate and iso-dodecyl 3-mercaptopropionate

IUPAC Name:

Reaction mass of iso-tridecyl 3-mercaptopropionate and iso-dodecyl 3-mercaptopropionate

Constituent 2

Reference substance name:

iso-Tridecyl 3-Mercaptopropionate

Molecular formula:

C16 H32 O2 S

IUPAC Name:

iso-Tridecyl 3-Mercaptopropionate

Constituent 3

Reference substance name:

iso-Tridecyl 3-Mercaptopropionate

IUPAC Name:

iso-Tridecyl 3-Mercaptopropionate

Constituent 4

Reference substance name:

Reaction mass of isotridecyl 3-mercaptopropionate and isododecyl 3-mercaptopropionate

EC Number:

929-442-0

Cas Number:

1040871-35-9

IUPAC Name:

Reaction mass of isotridecyl 3-mercaptopropionate and isododecyl 3-mercaptopropionate

Details on test material:

- Name of test material (as cited in study report): iso-tridecyl 3-mercaptopropionate
- Physical state: liquid
- Analytical purity: 99.7% w/w
- Purity test date: 1995-05-05
- Lot/batch No.: B98E2682
- Storage condition of test material: room temperature in the dark

comment: test substance used in this study
The study was performed with a test material identical to the submission substance (identical producer and identical way of synthesis). In the test report the test item is named iso-tridecyl-3-mercaptopropionate, which is used as the chemical name and as the trade name by the producer.

Test animals

Species:

rat

Strain:

other: Sprague-Dawley Crl :CD (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles RIver (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 203-227g (males), 204-217g (female)
- Fasting period before study: overnight fast before dosing
- Housing: in groups of up to three by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): free access to "Rat and Mouse Expanded Diet No. 1"; special diets services limited; Witham; Essex; UK
- Water (e.g. ad libitum): free access
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 47-64%
- Air changes (per hr): approximately fifteen
- Photoperiod (hrs dark / hrs light): 12h / 12h


IN-LIFE DATES: From: 2008-09-08 To: 2008-10-12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20, 50 and 200mg/mL
- Amount of vehicle (if gavage): 10mL/kg
- Justification for choice of vehicle: test substance did not dissolve in distilled water or other aqueous vehicles

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION (if unusual): formulations were dosed within 42 minutes of preperation

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 200mg/kg was suggested

Doses:

200, 500 and 2000mg/kg bw

No. of animals per sex per dose:

3 males and three females for dose group 200 and 500mg/kg bw;
3 females for dose group 2000mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4h after dosing and subsequently once daily (signs of toxicity); prior to dosing and 7 and 14 days after treatment (weighing)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and necropsy

Statistics:

not applicable

Results and discussion

Preliminary study:

none

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 - < 2 000 mg/kg bw

Mortality:

No mortalities were noted at 200 or 500 mg/kg bw. Two animals treated with 2000 mg/kg were found dead during the day of dosing and the remaining animal treated with 2000 mg/kg was found dead one day after dosing.

Clinical signs:

other: Common signs of systemic toxicity noted, prior to death, in animals treated with 2000mg/kg were hunched posture, lethargy, decreased respiratory rate, laboured respiration, prostation, tonic convulsions, increased salivation with incidents of pallor of th

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test material was determined to be greater than 500mg/kg but less than 2000mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the SpragueDawley CD strain rate. The method used was according to the "Acute toxic Class Method”.

Using all available information, 200mg/kg bodyweight was selected as the starting dose. A group of three fasted females was treated with the starting dose of 200mg/kg. This was followed by a group of three fasted males at the same dose level. Based on the results from this dose level a further group of fasted females was treated at a dose level of 2000mg/kg bodyweight and a further group of fasted males and females was treated at a dose leve of 500mg/kg bw. Dosing was performed sequentially.

 

The test material was administered orally as a solution in arachis oil. Clinical observations were performed 0.5 1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy.

 

Two females treated with 2000mg/kg were found dead during the day of dosing and the remaining female treated with 2000mg/kg was found dead one day after dosing. Clinical signs of toxicity noted, prior to death, in animals treated with 2000mg/kg were hunched posture, lethargy, decreased respiratory rate, laboured respiration, prostration, ataxia, increased salivation, tonic convulsions and pallor of the extremities. Clinical signs of toxicity noted in animals treated with 500mg/kg were hunched posture, up to one day after dosing. No clinical signs of toxicity were noted in animals treated with 200mg/kg. The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Mortalities were noted at a dose level of 2000mg/kg bodyweight. No mortalities were noted in animals treated with 200 or 500mg/kg bw.

The acute oral LD50 of the test material was determined to be greater than 500mg/kg but less than 2000mg/kg bw.