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Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In a reliable study, conducted to OECD guideline 406, Kalcol 2098 (Dodecan-1-ol (C12) was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Co.
- Age at study initiation: 5 weeks
- Weight at study initiation: 304 to 355 g
- Housing: 5/cage; aluminium cages with stainless steel wire mesh floors (350 x 400 x 200 mm)
- Diet (e.g. ad libitum): standard pelleted guinea pig diet (RC-4), ad libitum
- Water (e.g. ad libitum): tap water 5 um-filtered, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +- 2
- Humidity (%): 50 +- 10
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 24-Jun-1997 To: 04-Sep-1997
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
- 8 females
- concentrations for intracutaneous application: 10, 5, 3, 1, 0.3, 0.1, 0% in liquid paraffin
- concentrations for occluded epicutaneous application (presumably 7 days later): undiluted, 30 and 10% in liquid paraffin
- evaluated for skin irritation at 24, 48 and 72 hours after intracutaneous application
- evaluated for skin irritation at 3, 24 and 48 hours after epicutaneous application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, intracutaneous and occluded epicutaneous
- Exposure period: epicutaneous induction 7 days after intracutaneous induction; epicutaneous challenge 21 days after intracutaneous induction
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous induction in the shaved skin area (~ 4 x 6 cm), symmetrically on both sides of the midline in the scapular region, test animals received (a), (b) and (c), controls received (a), (d) and (a); epicutaneous induction at initially exposed skin site shaved again, test animals received (e), control animals received (d)
- Frequency of applications: epicutaneous induction 7 days after intracutaneous induction
- Duration: epicutaneous induction 48 hours
- Concentrations: (a) 1:1 water-in-oil emulstion of Freunds complete adjuvant (FCA) and physiological saline, (b) test material at 3% in liquid paraffin, (c) 1:1 emulsion of test material at 6% in FCA and physiological saline, (d) liquid paraffin, (e) 0.2 ml of test substance at 50% in liquid paraffin

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after intracutaneous induction
- Exposure period: 24 hours occlusive
- Test groups: 10 females
- Control group: 5 females
- Site: flank, clipped and shaved
- Concentrations: (f) 0.1 ml test substance at 10, 3 and 0% in liquid paraffin
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches

OTHER:
- General condition
- Body weight
- Rechallenge: not required
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene and formalin, not concurrent, results from 12 tests at same testing facility
Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenge: 0, 3 and 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenge: 0, 3 and 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenge: 0, 3 and 10%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenge: 0, 3 and 10%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no effects.

RESULTS OF PILOT STUDY: Following intradermal injection significant skin irritation was seen at concentrations of 5 and 10% persisting for 72 hours. The 3% concentration showed evidence of irritation at 24 hours only. Following topical application the undiluted material was irritant up to 48 hours, 2/4 guineapigs showed irritation at 10% while there was no evidence of irritation with the 3% concentration.

RESULTS OF TEST

- Sensitization reaction: There was no evidence of sensitisation in any of the test animals. Reactions at 24 and 48 hours following challenge with the solvent control (liquid paraffin) and 3% and 10% solutions were 0/10 treated, 0/5 control.

- Clinical signs: There were no significant differences in general condition and body weight gain between test and control groups over the course of the test.

- Rechallenge: Not required.

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In a reliable study, conducted to OECD guideline 406, Kalcol 2098 (Dodecan-1-ol (C12) was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.
Executive summary:

In a reliable study, conducted to OECD guideline 406, Kalcol 2098 (Dodecan-1-ol (C12) was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.

Dodecan-1-ol (C12) is supporting substance for Alcohols,C12-C14 and the main component.

Endpoint:
skin sensitisation: in chemico
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Kalcol 4098 (Tetradecanol (C14)) showed no evidence of being a skin sensitizer when tested using the Guinea pig maximization test in a reliable study conducted in accordance with OECD Guidelines 406. The study was GLP compliant.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Shizuoka
- Age at study initiation: 5 weeks
- Weight at study initiation: 313-337 g
- Housing: animals were housed in aluminium cages with stainless steel wire mesh floors (350 mm x 400 mm x 200 mm, Natsume Seisakusyo Co., Tokyo); 5 animals/cage.
- Diet (e.g. ad libitum): standard pelleted diet for guinea-pigs (RC-4; Oriental Yeast Co.) ad libitum
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):23±2
- Humidity (%): 50±10
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12hrs light

IN-LIFE DATES: 19-Jun-1997 to 04-Sep-1997
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING STUDY: A preliminary test was performed to assess primary skin irritation using 8 female guinea-pigs. Test substance was administered to four animals by intradermal injection (10%, 5%, 3%, 1%, 0.3% and 0.1% w/w) and to four animals by 24-hr occluded patch. The number of animals showing skin irritation was recorded at 24, 48 and 72 hrs after intradermal treatment and at 3, 24 and 48 hrs after occluded patch testing. The results of this test were used to determine the doses for intradermal injection, topical induction and topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 - intracutaneous, followed by epicutaneous 7 days later
- Exposure period: 21 days between initial induction and challenge
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous - intradermal injections were performed in the shaved skin area on both sides of the midline in the scapular region; epicutaneous - occlusive patches were applied to the previously treated areas
- Frequency of applications: intracutaneous induction followed by epicutaneous induction 1 week later
- Duration: epicutaneous induction - 48 hrs
- Concentrations: 5% intracutaneous, 50% epicutaneous

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Exposure period: 24 hrs
- Test groups: 10 females
- Control group: 5 females
- Site: flank
- Concentrations: 3%, 10 % (w/w)
- Evaluation (hr after challenge): 24, 48 hrs

OTHER:
Grading system used for evaluation of patch test results (Magnusson and Kligman) : 0 = no visible change, 1 = discrete or patch erythema; 2 = moderate and confluent erythema; 3 = intense erythema and swelling.

MAIN STUDY
Induction:
(Day 0) Intradermal injections of 0.1ml of each of following: (a) 1:1 (v/v) emulsion of Freund's complete adjuvant (FCA) and physiological saline, (b) 5% (w/w) of the test substance in liquid paraffin, and 1:1 (v/v) emulsion of 10% (w/w) test substance in FCA and physiological saline.
(Day 7) Occluded patches of 0.2 ml 50% (w/w) of the test substance in liquid paraffin were applied for 48 hrs.
Challenge:
(Day 21) Occluded patches of 0.1 ml of each of the 10%, 3% (w/w) of the test substance in liquid paraffin and liquid paraffin alone were applied for 24 hrs.
Challenge controls:
Five female animals were administered intradermally: 0.1 ml of liquid paraffin and 0.1 ml of an emulsion of Freund's complete adjuvant (FCA) and physiological saline. Seven days later an occluded patch of liquid paraffin was applied for 48 hrs. At the challenge exposure, occluded patches of paraffin were applied to the animals flanks for 24 hrs.
Positive control substance(s):
yes
Remarks:
DNCB and formalin, not concurrent
Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.

RESULTS OF RANGE FINDING STUDY:

Following intradermal injection, skin irritation was seen at concentrations of 10% and 5% persisting for 72 hours

but less marked at the lower concentration. The 3% concentration showed evidence of irritation at 24 hours in oneanimal only. Lower concentrations from 0.1 -1% showed no irritation. Following topical application slight irritation was seen in 2/4 animals at 50% only. 

TEST: There was no evidence of sensitisation in any of the test or control animals at either challenge concentration

 

Table 1. Summary of the delayed contact hypersensitivity study of KALCOL 4098 in female guinea-pigs

 

Group

Number of animals showing positive reaction/Total number of animals

24 hrs after challenge

48 hrs after challenge

10%

3%

vehicle

10%

3%

vehicle

Test

0/10

0/10

0/10

0/10

0/10

0/10

Control

0/5

0/5

0/5

0/5

0/5

0/5

 

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Kalcol 4098 (Tetradecanol (C14)) showed no evidence of being a skin sensitizer when tested using the Guinea pig maximization test in a reliable study conducted in accordance with OECD Guidelines 406. The study was GLP compliant.
Executive summary:

Kalcol 4098 showed no evidence of being a skin sensitizer when tested using the Guinea pig maximization test in a reliable study conducted in accordance with OECD Guidelines 406. The study was GLP compliant.

Tetradecanol (C14) ) is supporting substance for Alcohols,C12-C14 and the one of the component in Alcohols,C12-C14 .

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In a reliable study, conducted according to OECD guideline 406, Kalcohl 6098 (Hexadecan-1-ol (C16)) was not a skin sensitiser in guinea pigs.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., UK
- Age at study initiation: ~8-12 weeks
- Weight at study initiation: 376-454 g
- Housing: singly or in pairs, in solid-floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): Guinea pig FD1 diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 44-74
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 11-Mar-1996 To: 03-Jun-1996
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 1%
Epicutaneous induction: 50%
Epicutaneous challenge: 25 and 50%
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 1%
Epicutaneous induction: 50%
Epicutaneous challenge: 25 and 50%
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
Intradermal induction
- 1 animal received 4 x 0.1 ml injections of test material at 1% (w/v)
- erythema assessed at 1, 2, 3 and 7 days after injection
- concentration selected that caused only mild to moderate skin irritation and was well tolerated systemically
Epicutaneous induction
- 2 animals injected with Freund's Complete Adjuvant (FCA) 11 days prior to application of test material at 5, 10, 25 and 50% (w/w)
- clipped flanks, occlusive, 48 hours
- erythema and oedema assessed at 1, 24 and 48 hours after the end of exposure
- concentration selected that caused only mild to moderate dermal irritation
Topical challenge
- 2 animals, test material at 5, 10, 25 and 50% applied to clipped flanks, occlusively for 24 hours (after being treated in the same way as control animals in the main study for the previous 14 days)
- erythema and oedema assessed at 1, 24 and 48 hours after the end of exposure
- highest non-irritant concentration selected

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 simultaneous intradermal injections; followed one week later by epicutaneous application
- Exposure period: single timepoint for intradermal injections; 48 hour epicutaneous application 7 days later
- Test groups: 10 animals
- Control group: 5 animals
- Site: clipped shoulder region, 40 x 60 mm
- Frequency of applications: intradermal induction followed 7 days later by epicutaneous induction
- Duration: single timepoint for intradermal injections; 48 hour epicutaneous application 7 days later
- Concentrations:
- intradermal induction, each 0.1 ml: test animals (a) FCA:water 1:1, (b) 1% (w/v) test material in arachis oil, (c) 1% (w/v) test material in FCA:water 1:1; control animals (a) FCA:water 1:1, (b) arachis oil, (c) 50% w/v arachis oil in FCA:water 1:1
- epicutaneous induction, thick even layer on filter patch 20 x 40 mm: test animals 50% w/w in arcahis oil; control animals, arachis oil; occluded
- Evaluation: erythema and oedema assessed 1 and 24 hours after patch removal

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: epicutaneous challenge on day 21
- Exposure period: 24 hour epicutaneous application
- Test groups: 10 animals
- Control group: 5 animals
- Site: clipped flanks, 50 x 70 mm
- Concentrations: epicutaneous challenge, thick even layer on filter paper patch 20 x 20 mm, 25% and 50%, one to each flank; occluded
- Evaluation (hr after challenge): erythema and oedema assessed 24 and 48 hours after patch removal

OTHER:
- Body weight recorded at start and end of study
- Any other reactions noted when erythema and oedema evaluated
Challenge controls:
5 non-induced animals received challenge applications.
Positive control substance(s):
yes
Remarks:
not concurrent, ethyl 4-aminobenzoate, 2,4-dinitrochlorobenzene, neomycin sulphate, 2-mercaptobenzothiazole
Positive control results:
Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no effects.

RESULTS OF PILOT STUDY: Intradermal. Erythema (grade 2) observed at all injection sites, no systemic toxicity. Tested at 1% only. Topical application for induction (48 hour) minimal irritation at 5 and 10%, with 25 and 50% maximum erythema score 2 persisting to 48 hours after removal of patch. Topical application for challenge initial minimal response at 1 hour, no irritation at 24 and 48 hours. RESULTS OF TEST - Sensitization reaction: No sensitisation reaction in any of the test or control animals. Response 0/10 test, 0/5 controls. - Clinical signs: Body weights and weight gain over the observation period were comparable in test and control groups. One animal was killed after topical challenge, the reason was not given but this was not considered to affect the results of the test. Well defined - moderate erythema at the intradermal injection site 24 hours after induction, well defined erythema at 48 hours. Following topical induction very slight to well defined erythema was noted 1 hour after patch removal, very slight erythema observed in 2/10 test animals at 24 hours. No skin reactions following topical challenge. - Rechallenge: Not required.

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In a reliable study, conducted according to OECD guideline 406, Kalcohl 6098 (Hexadecan-1-ol (C16)) was not a skin sensitiser in guinea pigs.
Hexadecan-1-ol (C16) is supporting substance for Alcohols,C12-C14 and the one of the component in Alcohols,C12-C14 .
Executive summary:

Kalcol 6098(Hexadecan-1-ol (C16)) is not a skin sensitiser in the guinea pig when tested using the Magnusson and Kligman maximisation assay.

Hexadecan-1-ol (C16) is supporting substance for Alcohols,C12-C14 and the one of the component in Alcohols,C12-C14

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Kalcol 8098 is not a skin sensitiser when tested using the Magnusson and Kligman guinea pig maximization procedure.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS: Guinea pigs
- Strain: Dunkin Hartley
- Sex: male
- Source: David Hall, Staffs, UK
- Age: 8-12 weeks
- Weight at study initiation: 305 -419 g
- Number of animals: 10
- Controls: 5
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
- Concentrations used for induction: intradermal 1% in arachis oil, topical 50% in arachis oil.
- Concentration in Freuds Complete Adjuvant (FCA): 1%
- Challenge schedule: Day 21 topical challenge (24 hours occlusive)
- Concentrations used for challenge: 25 and 50% in arachis oil.
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
- Concentrations used for induction: intradermal 1% in arachis oil, topical 50% in arachis oil.
- Concentration in Freuds Complete Adjuvant (FCA): 1%
- Challenge schedule: Day 21 topical challenge (24 hours occlusive)
- Concentrations used for challenge: 25 and 50% in arachis oil.
No. of animals per dose:
10 test, 5 control
Details on study design:
ADMINISTRATION/EXPOSURE
- Study type: M&K maximisation procedure (adjuvant method)
- Preparation of test substance for induction: in arachis oil
- Induction schedule: Day 1 intradermal induction, day 7 topical induction (48 hours occlusive).
- Concentrations used for induction: intradermal 1% in arachis oil, topical 50% in arachis oil.
- Concentration in Freuds Complete Adjuvant (FCA): 1%
- Challenge schedule: Day 21 topical challenge (24 hours occlusive)
- Concentrations used for challenge: 25 and 50% in arachis oil.
- Rechallenge: No
- Positive control: Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.

EXAMINATIONS
- Grading system: Draize 0-4 scale for erythema and oedema.
- Pilot study: Topical (24 and 48 hour occlusive) applications were tested at 5, 10, 25 and 50%. Intradermal injection was attempted at 1 and 5% but the 5% solution was impossible to inject.
Challenge controls:
5 non-induced animals received challenge applications.
Positive control substance(s):
yes
Remarks:
Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.
Positive control results:
Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 and 50% (challenge). No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no effects.

RESULTS OF PILOT STUDY: Minimal erythema at 24 and 48 hours after 48 hour topical exposure, no irritation at these time periods after a 24 hour topical application. Well defined erythema (grade 2) at 24, 48 and 72 hours post injection reducing to slight erythema (grade 1) at 7 days.

RESULTS OF TEST

- Sensitization reaction: No positive responses with 25% or 50% challenge concentrations in test or control groups at 24 or 48 hours. 0/10 treated and 0/5 controls responded to challenge.

- Clinical signs: Body weights and weight gain over the observation period were comparable in test and control groups. Well-defined erythema was noted at the intradermal induction sites of all test group animals at 24 and 48hours. Very slight to well-defined erythema was noted at the intradermal sites of the control group at 24 and very slight erythema at 3 sites at 48 hours.

Very slight to well-defined erythema was noted at the induction sites of six test group animals at the 1 hour mark. No skin reactions were noted at the induction sites of any test group animals at the 24 hour mark.

- Rechallenge: Not carried out.

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Kalcol 8098 is not a skin sensitiser when tested using the Magnusson and Kligman guinea pig maximization procedure.
Classification: not sensitizing
Executive summary:

Kalcol 8098 is not a skin sensitiser when tested using the Magnusson and Kligman guinea pig maximization procedure.

Classification: not sensitizing

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

No evidence of skin sensitisation. It is concluded that the substance Alcohols, C12-14 does not meet the criteria to be classified for human health hazards for Inhalation - local effect: skin sensitisation.

 

In a reliable study, conducted to OECD guideline 406, Kalcol 2098 (Dodecan-1-ol (C12) was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.

Dodecan-1-ol (C12) is supporting substance for Alcohols,C12-C14 and the main component.

 In other study of Driscoll, R. 1996 the test substance (hexadecan-1-ol (as a read across)) is not sensitizing to skin.

In a reliable study, conducted according to OECD guideline 406, hexadecan-1-olwas not a skin sensitiser in guinea pigs.

 

 This result can be reliably be read across to the substance Alcohols, C12-14(CAS#  80206-82-2)

 

Synopsis

Not sensitising

  

Conclusion

Aliphatic alcohols do not have a skin sensitisation potential in animals. Based on human evidence, the allergenic potency of this category is very low.


 

 


Migrated from Short description of key information:
No evidence of skin sensitisation. It is concluded that the substance Alcohols, C12-14 does not meet the criteria to be classified for human health hazards for Inhalation - local effect: skin sensitisation.

Respiratory sensitisation

Link to relevant study records
Reference
Endpoint:
respiratory sensitisation: in vivo
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Respiratory sensitisation.

There are no Respiratory sensitisation studies available.

Due to the absence of chemical groups or other structural alerts this substance is not considered to exhibit an high hazard potential.

Alcohols, C12-14 is of low priority for further work based on a low hazard potential is of low priority for further work based on a low hazard potential.

There is no information available from single or repeated inhalation exposures in laboratory animals or from human experience allowing a conclusion on potential respiratory tract irritation and sensitisation of the aliphatic alcohols.

Therefore testing for Respiratory sensitisation does not need to be performed.


Migrated from Short description of key information:
There are no Respiratory sensitisation studies available.
Due to the absence of chemical groups or other structural alerts this substance is not considered to exhibit an high hazard potential.
Alcohols, C12-14 is of low priority for further work based on a low hazard potential is of low priority for further work based on a low hazard potential.
There is no information available from single or repeated inhalation exposures in laboratory animals or from human experience allowing a conclusion on potential respiratory tract irritation and sensitisation of the aliphatic alcohols.
Therefore testing for Respiratory sensitisation does not need to be performed.

Justification for classification or non-classification

Based on the hazard assessment of Alcohols, C12-14 in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99)and according to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Respiratory Sensitisation Xn

R42 May cause sensitization by inhalation

Respiratory Irritation Xi

R37 irritating to respiratory system

CLP

Respiratory Sensitisation

H334 Resp. Sens. 1 May cause allergy or asthma symptoms or breath-ing difficulties if inhaled

Respiratory Irritation

H335 STOT SE 3 May cause respiratory irritation

It is concluded that the substance Alcohols, C12-14 does not meet the criteria to be classified for human health hazards for Inhalation - local effect: respiratory sensitisation.