Registration Dossier

Administrative data

Description of key information

In a GPMT test Perkalink was tested positive in 19/20 animals; only 1/20 controls showed a positive reaction.

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:
August-October 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
The potential of BCI-MX (1,3-bis(3-methyl-2,5-dioxo-1H-pyrrolinylmethyl)benzene) to cause delayed contact hypersensitivity in guinea pigs was assessed by the Magnusson-Kligman Maximisation Test.
The closely clipped dorsa of ten male and ten female Dunkin-Hartley guinea pigs were subject to intradermal injections of Freund's Complete Adjuvant, 0.1% BCI-MX in propylene glycol an 0.1% BCI-MX in propylene glycol in the adjuvant on Day 1. Seven days later the same area of skin was treated by topical application of 10% BCI-MX in propylene glycol and the test site was covered by an occlusive dressing for 48 hours. The same induction procedures were carried out on a contemporaneous control group of ten male and ten female animals, except that the test material was replaced by vehicle in all doses.
On Day 22, all animals were challenged by occluded application of propylene glycol to the left flank and 3% and 0.3% BCI-HX in propylene glycol to two sites on the right flank. The occlusive dressings were removed on the following day and the condition of the test sites was assessed approximately 24 and 48 hours later.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Guinea pig Magnusson-Kligman test shown here was performed in 1993. At that time this method was the method of choice for testing of skin sensitization.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Concentration of test material and vehicle used at induction:
First induction (intradermal):
0.1 % w/v of the test item in propyleneglycol and 0.1 % w/v in propyleneglycol in FCA
Second induction (topical): 10% w/v of the test item in propyleneglycol
Concentration of test material and vehicle used for each challenge: 3 % w/v in propyleneglycol 0.3 % w/v in propyleneglycol

Concentration of test material and vehicle for primary irritation screen:
Induction (intradermal): 0.03 to 10 % w/v of the test item in propylene glycol or in propylene glycol in FCA (slight irritation at 0.1%)
Induction (topical): 5-50% w/v of the test item in propyleneglycol (no irritation at 5 and 10%)
Challenge: 1-5 % w/v in propyleneglycol (slight irritation)
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Concentration of test material and vehicle used at induction:
First induction (intradermal):
0.1 % w/v of the test item in propyleneglycol and 0.1 % w/v in propyleneglycol in FCA
Second induction (topical): 10% w/v of the test item in propyleneglycol
Concentration of test material and vehicle used for each challenge: 3 % w/v in propyleneglycol 0.3 % w/v in propyleneglycol

Concentration of test material and vehicle for primary irritation screen:
Induction (intradermal): 0.03 to 10 % w/v of the test item in propylene glycol or in propylene glycol in FCA (slight irritation at 0.1%)
Induction (topical): 5-50% w/v of the test item in propyleneglycol (no irritation at 5 and 10%)
Challenge: 1-5 % w/v in propyleneglycol (slight irritation)
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 20
Challenge controls:
Yes
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3 %
No. with + reactions:
17
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3 %
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
in total 19 animals responded at challenge with 3%
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
3
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
6
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
3 %
No. with + reactions:
1
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
3 %
No. with + reactions:
0
Total no. in group:
20
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3 %
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3 %
No. with + reactions:
0
Total no. in group:
20
Group:
positive control
Remarks on result:
not measured/tested

Maximum concentration not causing irritating effects in preliminary test: 10 %.
Signs of irritation during induction:

Intradermal induction gave rise to barely-perceptible to moderate erythema, pallor and discolouration.
Topical induction gave rise to barely perceptible or slight erythema, but eschar formation and exfoliation.
Evidence of sensitisation of each challenge concentration: A significant response was observed in 19 test and one control animal.

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Because 19 out of 20 animals showed a dermal response following challenge, versus one control animal, the test substance was considered aa a dermal sensitiser.
Executive summary:

A skin sensitization test according to OECD guideline 406 (Guinea Pig Maximization Test, GPMT) was conducted on guinea pigs with test substance formulations in propylene glycol of 0.1% for intradermal induction and 0.3 and 3% for topical induction. In the challenge phase of the experiment test concentrations of 3 and 0.3% (in propylene glycol) were applied. A significant response (slight erythema or a more marked reaction) was observed in 19 test and one control animal after challenge with 3%. Six test animals and no control animals responded to 0.3% of the test item. Thus, under the conditions of this assay the test item has to be regarded as skin sensitizer in Guinea pigs.

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

A skin sensitization test according to OECD guideline 406 (Guinea Pig Maximization Test, GPMT) was conducted on guinea pigs with test substance formulations in propylene glycol of 0.1% for intradermal induction and 0.3 and 3% for topical induction. In the challenge phase of the experiment test concentrations of 3 and 0.3% (in propylene glycol) were applied. A significant response (slight erythema or a more marked reaction) was observed in 19 test and one control animal after challenge with 3%. Six test animals and no control animals responded to 0.3% of the test item. Thus, under the conditions of this assay the test item has to be regarded as skin sensitizer in Guinea pigs.

Based on complaints in workers it was concluded that the test substance should be regarded as skin sensitizer for humans.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test item was shown to be a skin sensitizer in Guinea pigs and humans. The guideline-conform Guinea Pig Maximization Assay showed 95% responding animals after treatment with 0.1% test item for intradermal induction. According to CLP classification criteria (Regulation (EC) No 1272/2008) a self-classification with Skin Sens. 1A is warranted. The test substance is classified according to Regulation 1272/2008, Annex VI with Skin Sens. 1.