Registration Dossier

Administrative data

Endpoint:
immunotoxicity, other
Remarks:
Day 1: i.p.; Day 22: i.v.
Type of information:
experimental study
Adequacy of study:
key 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:
other: EEC guidelines
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
impurity
Type:
impurity
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 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 / concentrationsopen allclose all
Dose / conc.:
0 other: ml/kg bw
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.