Registration Dossier

Administrative data

Description of key information

Skin sensitisation:

Based on all the observation and results, it was concluded that the test chemical is sensitising on the basis of human studies and therefore is likely to be classified as a positive sensitiser as per the CLP criteria of classification and labelling.

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to guideline
Guideline:
other: Patch test
Principles of method if other than guideline:
Patch-Test was conducted to evaluate the dermal sensitization potential of the test chemical
GLP compliance:
not specified
Type of study:
patch test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.
Species:
human
Strain:
other: Not applicable
Sex:
female
Details on test animals and environmental conditions:
Age: 51 years
Source: St John’s Institute of Dermatology, London
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1% pet.
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1% pet.
Adequacy of challenge:
not specified
No. of animals per dose:
31
Details on study design:
No data available
Challenge controls:
Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to the test chemical at 0.01% and 0.032%
Key result
Reading:
1st reading
Group:
test chemical
Dose level:
2%, 1%, 0.32%, 0.1%,
No. with + reactions:
0
Total no. in group:
31
Clinical observations:
The substance provoked a +2 reaction
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Group:
test chemical
Dose level:
0.001% and 0.0001% in pet.
No. with + reactions:
0
Total no. in group:
31
Clinical observations:
No sensitisation was observed at these dose levels
Remarks on result:
other: Not-sensitizing
Reading:
1st reading
Group:
other: Control group
Dose level:
(0.01% and 0.032%..)
No. with + reactions:
1
Total no. in group:
31
Clinical observations:
Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to Solvent Orange 60 at 0.01% and 0.032%.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. Group: other: Control group. Dose level: Solvent Orange 60 (0.01% and 0.032%..). No with. + reactions: 1.0. Total no. in groups: 31.0. Clinical observations: Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to Solvent Orange 60 at 0.01% and 0.032%..
Interpretation of results:
other: sensitizing
Conclusions:
A (+2) reaction was obtained with the test chemical at the concentrations of 2%, 1%, 0.32%, 0.1%, 0.032% and 0.01% in petrolatum.
No sensitisation was observed at these dose levels of 0.001% and 0.0001% in petrolatum. Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to the test chemical at 0.01% and 0.032%.
Based on the reactions, the test chemical can be considered to be sensitizing to skin.
Executive summary:

The study reports of a peculiar case of contact dermatitis due to occupational exposure to the test chemical.

A 55-year-old woman, who had been working in a plastic manufacturing company since 1986, developed dermatitis affecting her wrists, fingers and face in 2008.

This eruption completely resolved during her time off. Her job involved assembling products such as welded plastic helmets. These helmets contained redcoloured

polyamide materials, and the manufacturer provided samples of them in granular form and the colours. Patch testing was carried out with filings using the test chemical, at concentrations of 2% pet., 1% pet., 0.32% pet.,0.1% pet., 0.032% pet., 0.01% pet., and 0.001% pet.,

A (+2) reaction was obtained with the test chemical at the concentrations of 2%, 1%, 0.32%, 0.1%, 0.032% and 0.01% in petrolatum.

No sensitisation was observed at these dose levels of 0.001% and 0.0001% in petrolatum. Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to the test chemical at 0.01% and 0.032%.

Based on the reactions, the test chemical can be considered to be sensitizing to skin.

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

Skin sensitisation

Various studies have been summarized to determine the ability of the test chemical to cause dermal sensitization in living organisms. These studies include in vivo experimental results on Guinea Pig and Human for the test chemical.

WoE 1:

The study reports of a peculiar case of contact dermatitis due to occupational exposure to the test chemical. A 55-year-old woman, who had been working in a plastic manufacturing company since 1986, developed dermatitis affecting her wrists, fingers and face in 2008. This eruption completely resolved during her time off. Her job involved assembling products such as welded plastic helmets. These helmets contained red coloured polyamide materials, and the manufacturer provided samples of them in granular form and the colours. Patch testing was carried out with filings using the test chemical, at concentrations of 2% pet., 1% pet., 0.32% pet.,0.1% pet., 0.032% pet., 0.01% pet., and 0.001% pet. A (+2) reaction was obtained with the test chemical at the concentrations of 2%, 1%, 0.32%, 0.1%, 0.032% and 0.01% in petrolatum. No sensitisation was observed at these dose levels of 0.001% and 0.0001% in petrolatum. Control studies on 31 patients gave negative results, except for 1 control, who had a +reaction to the test chemical at 0.01% and 0.032%. Based on the reactions, the test chemical can be considered to be sensitizing to skin.

WoE 2:

The study reports of an allergic reaction caused by the test chemical in humans after wearing spectacle frames. A 51-year-old woman developed an exudative dermatitis behind her ears 3 days after wearing a pair of newly fitted titanium-framed spectacles (A); these frames were acquired because of nickel allergy. She had another titanium spectacle frame (B) fitted, but she developed a similar dermatitis behind her ears. Her dermatitis resolved when she stopped wearing the glasses. She was patch tested with an extended European baseline series (Almirall Hermal, Reinbek, Germany), plastic and acrylates series (Chemotechnique Diagnostics, Vellinge, Sweden), and shavings from the plastic that coated the titanium arms that curve around the ears (‘temples’). Finn Chambers®on Scanpor®tape were used. The patient developed a +2 reaction (International Contact Dermatitis Research Group criteria) to shavings from frames (A) and (B). The patient was patch tested with test material 1% pet. Readings at D2 and D4 showed a +2 positive reaction to the test chemical.

Based on these reactions the test chemical can be considered to be sensitizing to skin.

WoE 3:

The study reports of a case of allergic reactions to the test chemical when present in the earpieces of spectacle frames. A 66-year-old man developed itchy infiltrative erythematous dermatitis behind his ears soon after he started to wear a new pair of metal framed spectacles (Spectacle A) at the beginning of 1995. He received occasional treatments with topical corticosteroid without much improvement. He bought another pair of metal-framed spectacles (Spectacles B) at the end of 1995 and wore them instead of Spectacles A, but the dermatitis did not clear. His dermatitis improved when he wore Spectacles C, a plastic-framed pair of spectacles, which he had used to wear before 1995. The patient was patch tested with scrapings of brown earpieces from Spectacles A and B (Earpieces) A and B) and the plastic frame of Spectacles C. The producers shared the detail regarding the components of ear pieces A, B, plastic frame of Spectacle C. The patient was tested for allergic reactions to the components of the earpiece A, earpiece B, spectacle frame as well as 25 standard allergens of the Japanese Society for Contact dermatitis. The reactions were observed and scored on Day 3. The patient reacted strongly positive to Colors A and B. Among 4 components of Color A, a +++ reaction was obtained with the test chemical 1% in petrolatum.This provoked a surrounding papulo-vesicular erythematous reaction over 10 cm in diameter, and induced several strong positive reactions to neighboring allergens (excited skin syndrome). When the test chemical was re-tested after 1 month, 0.1% petrolatum produced a +++ reaction on surrounding erythema. The test chemical 0.1% pet. and the pink color 1% pet. were patch tested on 5 normal control patients and all reacted negatively. Since even after 1 month after performing the initial test, a positive reaction was observed for the test chemical, hence it can be considered to be sensitizing to skin.

WoE 4

The study reports of allergic contact dermatitis caused by the test chemical when used in spectacle frames. A 45-year-old female developed itchy infiltrative erythematous peri-auricular dermatitis 6weeks after she started to wear new reddish-brown plastic spectacle frames ‘made in Japan’.The dermatitis spread to the upper part of the bilateral pinna. Patch tests were performed with Finn Chambers® (SmartPractice, Phoenix, AZ, USA) on Scanpor tape® (Norgesplaster, Vennesla, Norway) on the patient’s lateral upper arm. A reading was performed on day (D) 3 according to ICDRG criteria. The patient elicited a positive reaction to the scrapings of the plastic temple of the spectacle frames and the test chemical (+++)1.0–0.001% petrolatum. Ten controls had negative results with both dyes tested at 1% petrolatum. Upon enquiry, the producer stated that the causative spectacle frames were produced by use of a plastic plate made by a Hong Kong company, and that only the final assembly had been performed in Japan.Gas chromatography/mass spectrometrywas performed on an extract from the piece of the frames, and detected the following nine chemicals. Further patch testing with the above eight chemicals other than the test chemical gave negative results. Hence the test chemical can be considered to be sensitizing to skin.

WoE 5

The study reports of 10 patients, of whom 6 developed dermatitis in the retroauricular/ temporal area after wearing plastic spectacles. Ten patients, 2 males and 8 females, aged 43 to 71 years. Patch testing was performed between 2011 and 2017 with the Swedish baseline series and, in some patients, also a plastic series (Chemotechnique Diagnostics, Vellinge, Sweden), supplemented with an in-house test preparation of test chemical 1.0% petrolatum. Patch testing and readings were performed according to ICDRG guidelines, with Finn Chambers (diameter, 8 mm; Smart- Practice, Phoenix, Arizona) on Scanpor tape (Norgesplaster, Vennesla, Norway). The dose for the petrolatum preparations was 20 mg,5 and that for the liquid preparations was 15 μL, for a Finn Chamber. Patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017 Ten patients, 2 males and 8 females, aged 43 to 71 years, reacted positively to SO 60 0 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20 cm outside the test area, and consisted of erythematous, infiltrated skin with papules Hence, the test chemical can be considered to be sensitizing to skin.

Based on all the results obtained from the available studies, it was conclued that the test chemical is likely to be a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on all the available studies on the skin sensitization, the test substance is likely to be considered for classification in the category of 'Skin Sensitizer 1B' as per the CLP criteria of classification and labelling.