Octanoic acid, 6,8-dimercapto-

Endpoint summary

Description of key information

A acute oral toxicity study according to OECD 401 is available.

The acute oral median lethal dose (LD50) in female rats was calculated to be 576 mg/kg bodyweight

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:

20.07.1999 - 20.08.1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation:8-12 weeks
- Weight at main study initiation: 226 -245 g (males), 205 - 230 g (females)
- Fasting period: overnight immediately before dosing and for approx. 3-4 h after dosing
- Housing: in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food ( Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): free access to drinking water
- Acclimation period: 5 days

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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

Range-finding study: 2000, 1000, 600, 500 and 250 mg/kg
Main study: 1000, 707, 500 mg/kg

No. of animals per sex per dose:

Range-finding study: one male and one female per dose
Main study: five females per dose and additionaly five males for the 500 mg/kg dose group

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, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Day 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross lession, body weight, and other toxicological effects

Statistics:

Using the mortality data obtained, the actual oral median lethal dose (LD50) and 95 % confidence limits of the test material were calculated using probit method of Finney D J `Probit Analysis´1971, Cambridge University Press.

Preliminary study:

Undiluted:
All animals were found dead during the day of dosing or one day after dosing. Clinical signs of toxicity noted were ataxia, clonic convulsions, hunched posture, lethargy, ptosis, decreased respiratory rate, laboured respiration, body tremors or occasional body tremors, vasodilation and splayed gait.
Test material formulation:
There were no deaths. Hunched posture was commonly noted.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

576 mg/kg bw

Based on:

test mat.

Mortality:

Deaths were noted one day after dosing.

Clinical signs:

other: Hunched posture was commonly noted in all groups. Incidents of lethargy were noted in animals treated with 707 or 1000 mg/kg. Additional incidents of systemic toxicity noted in animals treated with 707 mg/kg were pilo-erection, occasional body tremors and

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, pale spleen, dark kidneys and sloughing of the non-glandular epithelium of the stomach. Scattered areas of white foci on the non-glandular epithelium of the stomach were noted at necropsy of one female and four male animals treated with 500 mg/kg that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of Lipoic Acid was determined to be 576 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of Dihydrolipoic Acid in the Sprague-Dawley CD strain rat. The method used was based was based on the recommendations of the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" and Method B.1 of Commision Directive 92/69/EEC.

Following a range-finding study, three groups of five fasted females were given a single oral dose of test material, as a solution in arachis oil BP at dose levels of 500, 707 and 1000 mg/kg bodyweight. A further group of five fasted males was similarly treated, at a dose level of 500 mg/kg bodyweight, to confirm that this sex was not markedly more sensitive to the test material. The surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

Deaths were noted one day after dosing. Clinical signs of toxicity noted were hunched posture, lethargy, pilo-errection, decreased rate, occasional body tremors and tiptoe gait. Surviving animals recovered two to five days after dosing.

Surviving animals showed expected gain in bodyweight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, pale spleen, dark kidneys and sloughing of the non-glandular epithelium of the stomach. Scattered areas of white foci on the non-glandular epithelium of the stomach were noted at necropsy of one female and four male animals treated with 500 mg/kg that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

The acute oral median lethal dose (LD50) and 95 % confidence limits of the test material were calculated by the probit method of Finney D J to be 576 (445 - 746) mg/kg bodyweight (female only)

Male animals were considered not to be markedly more sentitive to the test material than female animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

576 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was performed to assess the acute oral toxicity of Dihydrolipoic Acid in the Sprague-Dawley CD strain rat. The method used was based was based on the recommendations of the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" and Method B.1 of Commision Directive 92/69/EEC.

Following a range-finding study, three groups of five fasted females were given a single oral dose of test material, as a solution in arachis oil BP at dose levels of 500, 707 and 1000 mg/kg bodyweight. A further group of five fasted males was similarly treated, at a dose level of 500 mg/kg bodyweight, to confirm that this sex was not markedly more sensitive to the test material. The surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

Deaths were noted one day after dosing. Clinical signs of toxicity noted were hunched posture, lethargy, pilo-errection, decreased rate, occasional body tremors and tiptoe gait. Surviving animals recovered two to five days after dosing.

Surviving animals showed expected gain in bodyweight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver or patchy pallor of the liver, pale spleen, dark kidneys and sloughing of the non-glandular epithelium of the stomach. Scattered areas of white foci on the non-glandular epithelium of the stomach were noted at necropsy of one female and four male animals treated with 500 mg/kg that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

The acute oral median lethal dose (LD50) and 95 % confidence limits of the test material were calculated by the probit method of Finney D J to be576 (445 - 746) mg/kg bodyweight (female only)

Male animals were considered not to be markedly more sentitive to the test material than female animals.

Justification for classification or non-classification

According to Regulation (EC) No. 1272/2008 a LD50 of 576 mg/kg bodyweight results in a classifcation as "Acute toxicity (oral) - Category 4; H302").