Registration Dossier

Administrative data

Description of key information

The test item was tested for its skin sensitisation properties in an OECD 406 and GLP compliant study (Guinea Pig Maximisation Test (GPMT)). The test item is considered to not be sensitising (BASF SE, 30H0107/942046, 1995).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1995 when the GPMT was an accepted method to assess skin sensitization potential of a substance.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 2767
- physical state at ambient conditions: liquid
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
- Animal species: Guinea pigs
- Strain/quality: Pirbright White, Dunkin Hartley Crl: (HA)BR [SPF]
- Origin: Charles River GmbH - Wiga, Sulzfeld, FRG
- Sex: Female
- Age of the animals: Young adult animals
- Body weight range at the beginning of the study: 288 - 341 g
- Acclimatization period: 7 days before the beginning of the study in the laboratory for dermal toxicity

- Housing conditions: Air conditions: central air-conditioning system, 20 – 24° C and a relative humidity 30 – 70 %.
- Illumination period: 12 h light (6.00 a.m.- 6.00 p.m.) 12 h darkness (6.00 p.m.- 6.00 a.m.)
- Type of cage: Makrolon, type IV
- No. of animals per cage: 5

- Identification of the animals: Ear tag numbering
- Type of diet: Kliba Labordiät 341 (Kaninchen-Meerschweinchen-Haltungsdiät) ad libitum
- Supplier: Firma Klingentalmühle AG, Kaiseraugst, Switzerland
- Watering: Water ad libitum (tap water; about 2 g of ascorbic acid per 10 l water was added to the drinking water twice a week)
- Bedding: Granulat Typ 3/4 (staubfrei); SSNIFF

Feed analysis:
The feed used in the study was assayed for chemical and microbiological contaminants.

Drinking water analysis:
The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the Technical Services of BASF AG as well as for the presence of germs by a contract laboratory.

Analysis of the bedding:
The bedding is regularly assayed for contaminants (chlorinated hydrocarbons, heavy metals).

Route:
intradermal
Vehicle:
water
Concentration / amount:
test substance 5 % in 0.9 % aqueous NaCl solution or in Freund's adjuvant / 0.9 % aqueous NaCl solution or 0.9 % aqueous NaCl solution
Day(s)/duration:
day 0
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Day(s)/duration:
day 7 / 48 h
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Day(s)/duration:
day 21 / 24 h
No. of animals per dose:
Control groups 1 and 2: 5 animals/group
Test group: 10 animals
Details on study design:
PRETEST:
A pretest was performed to detect a possible influence on irritating effects of previous intradermal treatment with Freund's adjuvant and to test applicability of intradermal test substance formulation injection

GENERAL

Weight check of the individual animals:
at the beginning of the study (day 0) and at the end of the study (last day of observation) (with the exception of the 2nd control group).

General observations:
a check was made twice each workday and once on Saturdays, Sundays and on public holidays for general observations and for dead or moribund animals.

Preparation of the test substance formulations:
- immediately before test substance application with Ultraturrax or with a magnetic stirrer (only adjuvant preparation)
- Formulations of the test substance were prepared gravimetrically; all concentrations were determined in weight/weight.

A. INDUCTION EXPOSURE
- No. of exposures: intradermal induction in groups of two injections per animal and percutaneous induction
- Test group: 10 animals
- control group: two groups with each 5 animals
- Site: shoulder
- Frequency of applications: percutanous induction was carried out one week after intradermal induction

INTRADERMAL INDUCTION
- Test groups: intradermal injection 0.1 mL of (A) Freund's adjuvant / 0.9% aqueous NaCl-solution (1 :1), (B) Substance 5% in 0.9% aqueous NaCl- solution or (C) Substance 5% in (A)
- Control group: same injections as test group but without test substance
- Readings: 24 h after application

PERCUTANEOUS INDUCTION
- Exposure period: 48 h
- Test groups: 2 x 4 cm filter paper strips were applied to the skin of the shoulder under an occlusive dressing. The filter paper strip was soaked
in the test substance; thus, the animais were exposed to about 0.3 g of the test substance.
- Control group: untreated
- Readings: 24 h after beginning of the application

B. CHALLENGE EXPOSURE
- No. of exposures: single percutaneous exposure
- Day of challenge: 21 days after intradermal induction
- Exposure period: 24 h
- Test groups: 2 x 4 cm filter paper strips were applied to the skin of the intact shoulder under an occlusive dressing. The filter paper strip was soaked
in the test substance; thus, the animais were exposed to about 0.3 g of the test substance.
- Control group: Control group 1 was treated equivalent to test group, control group 2 remained untreated
- Readings: 48 and 72 h after begining of the application

Challenge controls:
Untreated animals (2. induction) and animals challenged with 5 % in 0.9 % aqueous NaCl solution or in Freund's adjuvant / 0.9 % aqueous NaCl solution or 0.9 % aqueous NaCl solution (1. induction)
Positive control substance(s):
yes
Remarks:
A positive control (reliability check) with a known sensitizer (1-chloro-2, 4-dinitrobenzene) was not included in this study.However, a separate study was performed twice a year in the laboratory.
Statistics:
Randomization:
According to Nijenhuis, A. and Wilf, H.S.: Combinatorial Algorithms, Academic Press, New York, San Francisco, London, 1978, pp. 62 - 64.
Positive control results:
A positive control (reliability check) with a known sensitizer was not included in this study. However, a separate study was performed twice a year in the laboratory.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The substance was assessed for its sensitizing effect on the skin using a Guinea Pig Maximisation Test (GPMT) in a GLP conform study according to OECD guideline 406 (BASF SE, 1995).

After the intradermal induction with the 5 % test substance preparations slight to well-defined signs of irritation could be observed in the test group animals. The percutaneous induction with the unchanged test substance led to partially open incrustations, well-defined erythema and slight edema in the test group animals. However, the challenge (21 days after intradermal induction) did not cause positive reactions 24 hours after test patch removal.

According to the present study, the test item does not exert a skin sensitizing effect.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as skin sensitizer under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.