Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Description of key information

Dermal sensitisation in guinea pigs: sensitizer

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, is well documented, and acceptable for assessment. Composition/purity of the test substance not reported.
Qualifier:
according to guideline
Guideline:
other: Maurer et al, 1975
Deviations:
not specified
GLP compliance:
no
Type of study:
Maurer optimisation test
Justification for non-LLNA method:
The study was conducted prior to the LLNA becoming the preferred method.
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy
- Weight at study initiation: 400 to 450 g
- Housing: individually in Macrolon cages, type 3
- Diet (e.g. ad libitum): NAFAG, Gossau SG pellets; ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1 deg C
- Humidity 55 +/- 5%
- Photoperiod (hrs dark / hrs light): 14 hours light / 10 hour dark

Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 mL
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 mL
No. of animals per dose:
20
Details on study design:
During the first week volumes of 0.1 mL of the test substance (0.1%) in saline without adjuvant were injected intradermally on Monday at two sites (flank and back), and on Wednesday and Friday at each one site on the back. Twenty-one hours after administration, the animals were chemically depilated with Butoquick and three hours later the skin reaction was assessed under artificial lighting. The two largest diameters of the erythematous reaction in vertical alignment were measured (mm) and the skin-fold thickness was determined with a skin-fold gauge (mm). The individual "reaction volume" (uL) was calculated from these values for each reaction from each animal.

During the second and third week of induction the substance was mixed with adjuvant (Bacto Adjuvant, complete Freund's Adjuvant) in a 1:1 ratio. A total of 6 sensitizing doses of 0.1 mL were injected intracutaneously into the skin of the neck on Monday, Wednesday and Friday. The reactions were not evaluated on these occasions. The test for skin sensitization was performed two weeks after the last sensitizing treatment with the adjuvant mixture. For the test 0.1 mL of the same substance formulation, as employed during the first testing week, was injected intradermally on the previously untreated flank. Twenty-four hours later the reaction site was evaluated in the same manner as during the first testing week.

A group of 20 guinea pigs treated in the same manner with the control vehicle alone served as negative and another group treated with Dinitrochlorobenzene as positive control.

For each animal the mean value plus one standard deviation was calculated for the reaction volumes of the 4 intracutaneous injections from the first testing week. Ten days after the intracutaneous challenge injection subirritant doses at the test compound were applied epicutaneously under occlusive dressing which were left in place for 24 hours.

Challenge controls:
Twenty guinea pigs were treated in the same way with the control vehicle alone served as the negative controls.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Significant skin sensitization
Rate of positive reactors: 20/20 animals
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Fisher's exact test
A positive reaction was observed.
Erythema scores (Draize scores), 24 hours after removal of dressing, by sex:
Males: 4/10 had a score of 1
Females: 7/10 had a score of 1
Interpretation of results:
other: Classified Category 1A according to EU criteria.
Conclusions:
Significant differences between the test group and the vehicle-treated controls were found with the test substance. The compound has therefore a skin sensitizing (contact allergenic) potential in albino guinea pigs.
Executive summary:

The optimization test was used, an intracutaneous sensitization procedure, to determine the sensitization potential of the test substance. The test was performed on groups of 10 male and 10 female guinea pigs. Dinitrochlorobenazene was used as the positive control. Skin sensitization was defined to occur for the challenge reaction whenever the reaction volume exceeded the mean value plus one SD of the 4 pre-sensitization reponses. Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were found with the test substance. Dinitrochlorobenzene caused significant skin sensitization potential in albino guinea pigs.

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

In a Maurer Optimization Test, the test substance was weakly sensitising to the skin of male and female albino guinea pigs. At 24 hours after removal of the dressing, the Draize scores for 4/10 males and 7/10 females were 1. Based on the results of a Buehler Test, a blend of the test substance in 50 % (w/v) acetone did not induce sensitisation in guinea pigs.  The optimisation testing protocol provides a more-sensitive measure of sensitisation than the Buehler method.
The key study was selected on the basis of the positive result obtained.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance requires classification with respect to skin sensitisation Category 1 (H317: May cause an allergic skin reaction).

In accordance with Annex VI, Regulation (EC) No 1272/2008, the substance has a harmonised classification with respect to skin sensitisation as Category 1A (H317: May cause an allergic skin reaction).