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Administrative data

Description of key information

A Guinea-pig maximisation test (OECD TG 406) showed that BMI is a skin sensitizer and should be classified as category 1A.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 October 1990 - 14 December 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was conducted in 1991 before the Local Lymph Node Assay was widely available. The GPMT was a standard and accepted method at the time at which the study was conducted. On the basis that pre-existing data are available for the skin sensitisation endpoint an additional test (LLNA) is not considered scientifically justified.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 300 - 376g
- Housing: Animals were housed in groups of up to three in solid-floor polypropylene cages furnished with softwood shavings.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 23°C
- Humidity (%): 46 - 67%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 31 October 1990 To: 14 December 1990
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Induction: 0.1% (w/v) in arachis oil or a 1:1 suspension of Freund's Complete Adjuvant plus arachis oil by injection; 50% (w/v) by topical application.
Challenge: 10% (w/v) in arachis oil.

A negative control group was also assessed, which recieved untreated arachis oil and a suspension of arachis oil and Freunds Complete Adjuvant during the induction phase.
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Induction: 0.1% (w/v) in arachis oil or a 1:1 suspension of Freund's Complete Adjuvant plus arachis oil by injection; 50% (w/v) by topical application.
Challenge: 10% (w/v) in arachis oil.

A negative control group was also assessed, which recieved untreated arachis oil and a suspension of arachis oil and Freunds Complete Adjuvant during the induction phase.
No. of animals per dose:
20 animals in the test group; 10 animals in the control group.
Details on study design:
RANGE FINDING TESTS:
Injections made with 5%, 1%, 0.5%, and 0.1% (w/v); injection sites were assessed for local necrosis, ulceration, or signs of toxicity, and the highest concentration which caused none of these was used for the intradermal stage of the induction process.
48-hour topical applications were made on two guinea pigs (intradermally injected with Freund's Complete Adjuvant 7 days earlier); applications of 50%, 25%, 10%, and 5% (w/w) test material in arachis oil were made; the highest concentration which only caused mild to moderate irritation was selected at the concentration to be used.
50%, 25%, 10%, and 5%(w/v) preparations of the test material in arachis oil were applied occlusively to the flanks of two guinea pigs for a period of 24 hours. The guinea pigs tested had been treated identically to the control animals of the main study up to day 14.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1 series of injections, and 1 topical application)
- Exposure period: The topical application was made one week after the injections. The topical application (occlusive dressing) lasted for 48 hours.
- Test groups: intradermal injections: Three injections (0.1 mL); (i) Freunds Complete Adjuvant and water, 1:1; (ii) 0.1% (w/v) suspension of test material in arachis oil; (iii) 0.1% suspension of test material in a 1:1 preparation of Freunds Complete Adjuvant and arachis oil. Topical application: 0.2 - 0.3 mL application of a 50% (w/w) suspension of test material in arachis oil.
- Control group: As above, but without tet material in each case.
- Site: Shoulder
- Frequency of applications: One single series of injections, followed by a single topical application 7 days later.
- Duration: Topical application was kept in place for 48 hours.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- Site: Flank
- Concentrations: 10% (w/v) in arachis oil.
- Evaluation (hr after challenge): 24, 48, and 72 hours after removal of occlusive dressing.

Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% (w/w)
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
Incidents of well-defined oedema noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% (w/w)
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
Incidents of well-defined oedema and desquamation noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
The test material produced a 60% sensitisation rate and was classified as a moderate sensitiser to guinea pig skin.
Executive summary:

A Guinea-pig maximisation test was performed as described in OECD test guideline 406, consisting of an intradermal (0.1% (w/v)) and epidermal induction and an epicutaneous challenge at day 21. The dermal response following 24 hr after the challenge to 10% of chemical resulted in clinical effects (edema) in 45% of test animals. The dermal response following 48 hr after the challenge to 10% (w/v) of chemical resulted in clinical effects (edema and desquamation) for 60% of test animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The key study was performed according to the Guinea-pig maximisation test as described in OECD test guideline 406, consisting of an intradermal (0.1% (w/v)) and epidermal induction and an epicutaneous challenge at day 21. The dermal response following 24 hr after the challenge to 10% of chemical resulted in clinical effects (edema) in 45% of test animals. The dermal response following 48 hr after the challenge to 10% (w/v) of chemical resulted in clinical effects (edema and desquamation) for 60% of test animals.

Justification for selection of skin sensitisation endpoint:

The Guinea Pig study was conducted in accordance with GLP and to international guidelines and is therefore reliable and has been designated the key study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a guinea pig maximisation test, a 0.1% intradermal induction dose elicited a positive sensitisation response in 60% (12 animals out of 20) guinea pigs. According to the criteria described in the CLP regulation (as Amended for Technical Progress by Commission Regulation 286/2011), BMI therefore meets the criteria for inclusion in Category 1A for skin sensitisation.

The relevant Hazard Statement is "H317: May cause an allergic skin reaction".

No data is available by which the classification with respect to respiratory sensitisation may be considered.