Metformin hydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

Individual scores are not provided

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1979

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: J. Officiel de la Republique Francaise (1971). Methodes officielles d’analyse des cosmetiques et produits de beaute. Annexe II: Methode officielle pour la determination de i’irritation oculaire. Arrete du 16 Avril 1973. Journal Officiel 21 April. p. 3953.

Version / remarks:

1973

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Association Francaise de Normalisation (1982). Evaluation de lrritation et/au de la Corrosion Cutanie chez le Lapin. NF T03-263

Version / remarks:

1982

Principles of method if other than guideline:

The study compared the results of three different in vivo test methods for the investigation of skin irritation in rabbits: (i) the OECD method (used for this endpoint study record), (ii) a method published by French authorities for the testing of cosmetics and toiletries and (iii) a method proposed by AFNOR (Association Francaise de Normalisation).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Metformin hydrochloride

EC Number:

214-230-6

EC Name:

Metformin hydrochloride

Cas Number:

1115-70-4

Molecular formula:

C4H11N5.ClH

IUPAC Name:

N,N-dimethylimidodicarbonimidic diamide hydrochloride

Test material form:

solid: bulk

Remarks:

migrated information: powder

Specific details on test material used for the study:

Beige Powder
Purity: no data
Storage: no data
Expiration: no data

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Roucher SA, Couhé.
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg.
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 g of moistended test material

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours and after 7 days and 14 days

Number of animals:

6 animals for each protocol (OECD, Cosmetics, AFNOR)

Details on study design:

TEST SITE
- Area of exposure: 6 cm x cm
- % coverage: 100
- Type of wrap if used: gauze pad (semiocclusive) or occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 1, 24, 48, and 72 hours and after 7 days and 14 days

SCORING SYSTEM:
- Method of calculation:cf. Draize, Woodard & Calvery (1948)


Criteria used for interpretation based on Primary Dermal Irritation Index (PDII) according to AFNOR scale:
PDII below 0.5.................non irritant
0.5-3................................slightly irritant
3-5...................................moderately irritant
5-8...................................severely irritant

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.13

Max. score:

8

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

Individual scores for each animal are not provided

Irritant / corrosive response data:

Non irritant based on OECD protocol

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material is not irritant to the skin of rabbits in this semi-occlusive istudy when tested according to the OECD protocol.

Executive summary:

In a non-GLP primary dermal irritation study (Guillot and al, 1982) performed similarly to the OECD No. 404, six male New Zealand White rabbits were dermally exposed to 0.5 g of undiluted Metformin HCl to the dorsal surface of the trunk (skin was clipped before application) for 4 hours under an semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after patch removal using the Draize scale. The irritancy of the test item was then defined on the basis of the the primary cutaneous index (PCI, comparable to the Primary Dermal Irritation Index PDII) using the scale appropriate for AFNOR.

The PCI/PDII is 0.13 (OECD protocol, maximum possible score = 8), the test substance was therefore considered as non-irritant to the skin.

Under the conditions of this test, no classification for skin irritation is required according to the criteria of the CLP Regulation (EC) N°1272/2008 and the Directive 67/548/EEC.