5-(dithiolan-3-yl)valeric acid

Immunotoxicity

Administrative data

Endpoint:

immunotoxicity, other

Remarks:

Day 1: i.p.; Day 22: i.v.

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

11/1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Study owner prepared study while seeking authorisation of the substance as active incredient for medical treatment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EEC guidelines

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-(dithiolan-3-yl)valeric acid

EC Number:

214-071-2

EC Name:

5-(dithiolan-3-yl)valeric acid

Cas Number:

1077-28-7

Molecular formula:

C8H14O2S2

IUPAC Name:

5-(1,2-dithiolan-3-yl)pentanoic acid

impurity 1

Reference substance name:

unknown

IUPAC Name:

unknown

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

dihydrogen oxide

Test material form:

solid: bulk

Details on test material:

This composition is the usual techical grade of AlzChem AG. It will be used when test substance has this composition (or is very closed) or no specific information is available

Specific details on test material used for the study:

10 ampoules à 10 ml (25 mg/ml alpha-Lipoic acid)
One part stored at room temperature
One part stored at -14 °C to -16 °C (max. -18 °C) for 4 weeks before application and then allowed to reach room temperature over a period of approximately 4 h on the day of application.

Test animals

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male

Details on test animals or test system and environmental conditions:

B.w.: 362 - 475 g
Age: 70 d on day of application
Housing: MAKROLON-cages (type III)
Room temperature: 21 °C +/- 2 °C
Relative humidity: 50 % +/- 10 %
Illumination: 150 lux at 1.5 m room height
Darkness: 12 h/d
Bedding: Granulated textured wood
Food: ALTROMIN 3022 (Standard Diet for Guiea Pigs), ad libitum
Water: ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

not specified

Details on exposure:

Day 1: i.p. injection
Day 22: iv injection

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: ml/kg bw

Doses / concentrations 2

Dose / conc.:

0.86 other: ml/kg bw

No. of animals per sex per dose:

7 m: 1 ml/kg bw horse serum
7 m: 1 ml/kg bw horse serum + test item stored at rt
7 m: test item stored at rt
7 m: 1 ml/kg bw horse serum + test item stored in freezer
7 m: test item stored in freezer

Control animals:

yes

Details on study design:

Day 1: injection of the test item i.p.
Day 22: injection ot the test item i.v.
In case of no observations: injection of 1 ml/kg bw hores serum i.v., one animal per group

Examinations

Observations and clinical examinations performed and frequency:

Signs of anaphylactic shock:
- licking nose or rubbing the nose with forefeet
- ruffling of fur
- laboured breathing
- sneezin or coughing (tree or more times)
- retching
During i.v. administration and for 15 min following the injection.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

no animal showed any sings of an anaphylactic shock after i.p. administration of the test item on day 22.
One animal of each group was treated with horse serum (1 ml/kg bw) on day 22: animals who recieved horse serum on day 1 immediatly showed signs of an anaphyactic shock (rubbing the nose, laboured breathing, convulsions and death).

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

3 animals who recieved horse serum on day 1 and day 22 died.

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

no effects observed

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Specific immunotoxic examinations

Cell viabilities:

not examined

Humoral immunity examinations:

not examined

Specific cell-mediated immunity:

not examined

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

>= 0.86 other: ml/kg bw

Based on:

test mat.

Sex:

male

Basis for effect level:

clinical signs

Remarks on result:

not determinable due to absence of adverse toxic effects

Applicant's summary and conclusion

Conclusions:

Single administration of alpha-Lipoic acid does not lead to sensitisation.

Executive summary:

Under the present test conditions, i.p. administration of 0.86 ml/kg bw alpha-Lipoic acid, either with or without concurrent administration of horse serum, did not possess any sensitising properties; ie. no positive sings of anaphylaxis were observed following i.v. administration of alpha-Lipoic acid on test day 22.

In this experiment, no differences were evident between the aninmals treated with alpha-Lipoic acid wich had been stored at rt and alpha-Lipoic acid wich had been stored at -14 °C to -16 °C for 4 weeks before application and then allowed to reach rt over a period of approx. 4 h on the day of application.

The sensitivity of the animals was tested by i.v. application of horse serum th one animal per group. This resulted in immediate signs of anaphylactic shock (rubbing the nose, laboured breathin, convulsions and death) in the animals wich had recieved horse serum (groups 1, 2 and 4). No effect was observed in the animals in groups 3 and 5.