Extract obtained from powder of Theobroma cacao (Malvaceae) by co-extraction with ethanol and propylene glycol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study predates GLP and OECD guideilnes, published in peer-reviewed literature, restrictions in design and reporting, but contributing to the overall assessment.

Data source

Reference

Reference Type:

publication

Title:

Lack of toxicity and carcinogenicity of some commonly used cutaneous agents

Author:

Stenbäck F, Schubik P

Year:

1974

Bibliographic source:

Toxicology and Applied Pharmacology, 30, 7-13

Materials and methods

Principles of method if other than guideline:

0.02 ml of the test substance (neat, 50% and 10% solution in acetone) were dropped on the dorsal skin between the flanks of 50 mice/group twice a week on a 1-inch square area which was shaved regularly. The animals were checked weekly, and all lesions and tumors were recorded. Animals were allowed to die spontaneously or were killed when moribund. Complete autopsies were performed on all animals. The skin from all animals, all grossly observed tumors and other lesions in the lungs, livers, kidneys etc., from treated as well as control groups were studied histologically.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propane-1,2-diol

EC Number:

200-338-0

EC Name:

Propane-1,2-diol

Cas Number:

57-55-6

Molecular formula:

C3H8O2

IUPAC Name:

propylene glycol

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Eppley colony
- Age at study initiation: 7 weeks
- Housing: in plastic cages with commercial bedding, 10/cage
- Diet: commercal diet, ad libitum
- Water: libitum

Administration / exposure

Type of coverage:

open

Vehicle:

acetone

Details on exposure:

TEST SITE
- Area of exposure: 1-inch square
- % coverage: 0
- Type of wrap if used: none
- Time intervals for shavings or clipplings: regularly


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.02 ml
- Concentration (if solution): 100, 50 and 10%
- Constant volume used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.02 ml

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Lifespan

Frequency of treatment:

Twice a week

Doses / concentrations

Remarks:

Doses / Concentrations:
10%, 50% and 100% in 0.02 ml acetone
Basis:

No. of animals per sex per dose:

50 females/dose

Control animals:

other: 135 untreated animals served as controls, 50 animals were treated with the solvent alove; 50 were treated with 7,12-dimethylbenzanthracene as a positive control

Details on study design:

- Rationale for animal assignment (if not random): the animals were randomized prior to the start of the experiments; the littermates were separated.

Positive control:

7,12-dimethylbenzanthracene

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly; all lesions and tumors were recorded.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes. The skin from all animals, all grossly observed tumors and other lesions in the lungs, livers, kidneys etc. from treated as well as control groups were studied histologically.

Statistics:

The statistical significance of the results was evaluated using the methods presented by Armitage (1971).

Results and discussion

Results of examinations

Clinical signs:

not specified

Dermal irritation:

not specified

Mortality:

not specified

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

No substance-related tumor increases were evidenced in mice treated with monopropylene glycol at different concentrations.

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 0.02 other: ml/twice a week

Sex:

female

Basis for effect level:

other: No substance-related tumor increases were evidenced with neat monopropylene glycol.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The dermal NOAEL was 0.2ml/twice a week in mouse.