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Diss Factsheets

Administrative data

Description of key information

Several studies are available:
HRC 1994: The study is performed to assess the skin sensitization potential of the substance using guinea-pig, according to EU Method B6 under GLP. The following dose levels were administered: Intradermal injection 5%, topical application 30%, and challenge application 25% and 12.5%. Ten test and five control animals were used. The substance produced evidence of skin sensitization in six of ten test animals.


HLS 2001: The study is performed to assess the skin sensitization potential of the substance using guinea-pig, according to OECD Guideline 406 under GLP. The test substance as supplied was administered in both induction and challenge stage. Twenty test and ten control animals were used. The substance did not produce evidence of skin sensitization in any of test animals.


Harlan 2011: The study is performed to assess the skin sensitisation potential of the substance in mouse, according to OECD Guideline 429 under GLP. Three groups, each of four animals, were treated with test item at 25%, 10% or 5%. A further group of four animals were treated with vehicle alone. The SI values are determined as 1.32, 2.48 and 1.38 for 5%, 10% and 25% groups, respectively. The substance is considered to be a non-sensitiser in this test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 24 May to 14 June 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
Lot number: A
Purity: >99%
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23 g
- Housing: individually housed in suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
25, 10, 5% v/v
No. of animals per dose:
4 mice each group
Details on study design:
PRE-SCREEN TESTS:
- Irritation: did not produce excessive local irritation at 25, 50%
- Systemic toxicity: did not produce systemic toxicity at 25%, one animal died at 50%

MAIN STUDY
Test item administration:
Mice were treated daily application of 25 uL of test item to dorsal surface of each ear for three consecutive days.
3H-Methyl thymidine administration:
5 days following first topical application of test item, all mice injected with 250 uL of PBS containing 3H-Methyl thymidine.
Observations:
All animals were observed twice daily on days 1, 2, 3 and daily basis on days 4, 5, 6. Bodyweight of each mouse was recorded on day 1 and day 6.
Terminal procedures:
5 hours after administration of 3HTdR all mice were killed by carbon dioxide asphyxiation. The draining auricular lymph nodes from the four mice were excised and pooled for each experiment group. For each group 1 mL of PBS was added to the pooled lymph nodes.
A single cell suspension of pooled lymph node cells was prepared by gentle mechanical disaggregation through 200-mesh stainless steel gauze. 3HTdR incorporation was determined after 8 hours incubation.

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The test item will be regarded as sensitiser if at least one concentration of test item results in threefold or greater increase in 3HTdR incorporation compared to control values.
Positive control substance(s):
not specified
Key result
Parameter:
SI
Value:
1.32
Test group / Remarks:
5% v/v
Key result
Parameter:
SI
Value:
2.48
Test group / Remarks:
10% v/v
Key result
Parameter:
SI
Value:
1.38
Test group / Remarks:
25% v/v
Cellular proliferation data / Observations:
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Slight redness on the ears was noted in two animals treated with test item at concentration of 25% v/v.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is considered to be a non-sensitiser in this test.
Executive summary:

The study is performed to assess the skin sensitisation potential of the substance in mouse, according to OECD Guideline 429 under GLP. Three groups, each of four animals, were treated with test item at 25%, 10% or 5%. A further group of four animals were treated with vehicle alone.


The SI values are determined as 1.32, 2.48 and 1.38 for 5%, 10% and 25% groups, respectively. The substance is considered to be a non-sensitiser in this test.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 11 January to 21 February 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
the study was performed before amendment of Annex VII and VIII
Specific details on test material used for the study:
Batch number: 60513F07
Purity: 99.81%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, England
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 308-371 g
- Housing: housed in groups of 10 in suspended metal cages with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30-70%
- Air changes: 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hours period
Route:
intradermal
Vehicle:
water
Concentration / amount:
5% v/v
Day(s)/duration:
single injection
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
30% v/v
Day(s)/duration:
48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
12.5, 25% v/v
Day(s)/duration:
2 weeks after final induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals
Details on study design:
RANGE FINDING TESTS: injection induction 5% v/v, topical induction 30% v/v, challenge 25 and 12.5% v/v. The results showed 25% v/v is considered to be maximum concentration would not give rise to irritating/adverse effects.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: single injection, and 48 hours for topical induction
- Site: injection at dorsal skin on scapular region, topical induction at interscapular area
- Frequency of applications: one week after injection, topical induction performed

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after final induction
- Exposure period: 24 hours
- Site: left flank, 20*20 mm
- Concentrations: 12.5, 25% v/v
- Evaluation (hr after challenge): 24, 48 and 72 hours after removal of patches
Challenge controls:
5 animals, 12.5, 25% v/v in water
Positive control substance(s):
yes
Remarks:
formalin
Positive control results:
Formalin produced evidence of skin sensitization in all animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
localised dermal reaction, necrotic patch; no signs of ill health or toxicity
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% v/v
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
localised dermal reaction, necrotic patch, tickening, dryness and sloughing of epidermis; no signs of ill health or toxicity
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The substance produced evidence of skin sensitization in six of ten test animals.
Executive summary:

The study is performed to assess the skin sensitization potential of the substance using guinea-pig, according to EU Method B6 under GLP.


The following dose levels were administered: Intradermal injection 5%, topical application 30%, and challenge application 25% and 12.5%.


Ten test and five control animals were used. The substance produced evidence of skin sensitization in six of ten test animals.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 19 July to 27 August 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
the study was performed before amendment of Annex VII and VIII
Specific details on test material used for the study:
Batch number: 06104056
Purity: 99.68%
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, England
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 weeks
- Weight at study initiation: 312-442 g
- Housing: housed in groups of 5 in suspended metal cages with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hours period
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% as supplied
Day(s)/duration:
15 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% as supplied
Day(s)/duration:
2 weeks after final induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals
Details on study design:
RANGE FINDING TESTS: 25, 50, 75, 100% v/v to 4 animals, no sign of irritating effects. Test material administered topically as supplied in main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours each exposure
- Site: left shoulder region, 2*2 cm
- Frequency of applications: on days 1, 8 and 15
- Duration: 15 days
- Concentrations: 100% as supplied

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after final induction
- Exposure period: 6 hours
- Site: right flank, 2*2 cm
- Concentrations: 100% as supplied
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
10 animals, 100% as supplied
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde
Positive control results:
HCA produced evidence of skin sensitization in all of 10 animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% as supplied
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no deaths, no signs of ill health or toxicity, no dermal reactions
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% as supplied
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no deaths, no signs of ill health or toxicity, no dermal reactions
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The substance did not produce evidence of skin sensitization in any of test animals.
Executive summary:

The study is performed to assess the skin sensitization potential of the substance using guinea-pig, according to OECD Guideline 406 under GLP. The test substance as supplied was administered in both induction and challenge stage. Twenty test and ten control animals were used. The substance did not produce evidence of skin sensitization in any of test animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation:
One guinea-pig study give positive result, another guinea-pig study give negative result; LLNA study give negative result.
Given the substance shows skin sensitizing potential in a reliable study, according to Regulation (EC) No 1272/2008, table 3.4.2, this substance should be classified as Category 1 for this endpoint.