Pentaerythritol tetrakis(3-mercaptopropionate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-08-20 through 2002-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerythritol tetrakis(3-mercaptopropionate)

EC Number:

231-472-8

EC Name:

Pentaerythritol tetrakis(3-mercaptopropionate)

Cas Number:

7575-23-7

Molecular formula:

C17H28O8S4

IUPAC Name:

3-[(3-sulfanylpropanoyl)oxy]-2,2-bis({[(3-sulfanylpropanoyl)oxy]methyl})propyl 3-sulfanylpropanoate

Details on test material:

- Name of test material (as cited in study report): PET-3-MP
- Physical state: liquid
- Analytical purity: 97.3%
- Purity test date: 2002-06-24
- Lot/batch No.: 2518
- Expiration date of the lot/batch: no data
- Stability under test conditions: guaranteed by the sponsor
- Storage condition of test material: approximately 4°C in the dark, under nitrogen

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman, Hull, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 167-215 g
- Fasting period before study: yes
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2002-08-20 To: 2002-09-02

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30, 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve in distilled water.
- Purity: BP grade

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Information from the sponsor suggested a starting dose of 300 mg/kg.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity %, 1, 2 and 4 hours after dosing
and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

not applicable for ATC method

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Remarks on result:

other: Estimated using the ATC flowchart

Mortality:

Two animals treated with 2000 mg/kg were found dead four hours or two days after dosing. One animal treated with 2000 mg/kg was killed in extremis one day after dosing. There were no deaths noted in animals treated with 300 mg/kg.

Clinical signs:

other: Signs of systemic toxicity noted in animals treated with 2000 mg/kg were hunched posture, increased lachrymation, clonic andlor tonic convulsions, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, loss of righting reflex, ataxia and

Gross pathology:

Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were abnormally red lungs, dark liver, slight haemorrhage or sloughing of the gastric mucosa and slight haemorrhage of the non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

EU classification: Xn, R22: Harmful if swallowed.
EU-GHS classification: Warning, Acute Tox. 4, H302: Harmful if swallowed.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat in accordance with OECD TG 423.

group of three fasted females was treated with the test material at a dose level of
300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 2000 and 300 mg/kg bodyweight. Dosing was performed sequentially.
The test material was administered orally as a solution in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.
Two animals treated with 2000 mg/kg were found dead four hours or two days after dosing. One animal treated with 2000 mg/kg was killed in extremis one day after dosing. There were no deaths noted in animals treated with 300 mg/kg.
Clinical Observations. Signs of systemic toxicity noted in animals treated with 2000 mg/kg were hunched posture, increased lachrymation, clonic and/or tonic convulsions, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, loss of righting reflex, ataxia and hypothermia.
One animal treated with 2000 mg/mg was found comatose. Signs of systemic toxicity noted in animals treated with 300 mg/kg were hunched posture, increased lachrymation, clonic and/or tonic convulsions and pilo-erection. There were no signs of systemic toxicity noted in three animals treated with 300 mg/kg.
The surviving animals showed expected gains in bodyweight over the study period.

Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were abnormally red lungs, dark liver, slight haemorrhage or sloughing of the gastric mucosa and slight haemorrhage of the non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

The acute oral median lethal dose (LDso) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 1000 - 2000 mg/kg bodyweight.