Fatty acids, coco, esters with 1,3-butanediol

Endpoint summary

Description of key information

Skin sensitisation (GPMT, OECD 406): not sensitising

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:

05 Aug 2004 - 11 Oct 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

yes

Remarks:

Challenge on day 27 instead of day 20-22; lack of details on topical induction exposure; lack of details in report; no rechallenge conducted; no justification for non-LLNA method

GLP compliance:

yes (incl. QA statement)

Remarks:

Groupe Interministeriel des Produits Chimiques, Paris, France, 2004

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No justification was given in the study report.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Centre de Production animale (F-45160 Olivet)
- Females (if applicable) nulliparous and non-pregnant: not stated
- Microbiological status of animals, when known: not stated
- Age at study initiation: not stated
- Weight at study initiation: 267g - 392g
- Housing: not stated
- Diet: not stated
- Water: not stated
- Acclimation period: 5 days
- Indication of any skin lesions: not stated

ENVIRONMENTAL CONDITION
- Temperature (°C): 17-25
- Humidity (%): 48-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): not stated
- IN-LIFE DATES: 19 Aug 2004 - 24 Sep 2004 (main study)

Route:

intradermal

Vehicle:

unchanged (no vehicle)

Concentration / amount:

a) 100 % (pure test material), b) 50 % FCA in physiological saline, c) 50 % FCA mixed 1:1 with pure test material

Day(s)/duration:

1st induction by injection on day 0

Adequacy of induction:

highest technically applicable concentration used

Route:

other: epicutaneous (occlusive dressing not stated)

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100 % pure test material

Day(s)/duration:

not stated (application on day 7)

Adequacy of induction:

other: skin pre-treated with 10% sodium lauryl sulfate

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

on day 27 / 24-hour exposure

Adequacy of challenge:

highest non-irritant concentration

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

50%

Day(s)/duration:

on day 27 / 24-hour exposure

Adequacy of challenge:

other: half of highest non-irritating concentration

No. of animals per dose:

10 animals were in the treated group; each of these 10 animals was challenged with 50% (in paraffin oil) and 100% pure test material on different anatomical sites

Details on study design:

RANGE FINDING TESTS:
Pre-test in 2 female guinea pigs by:
- intradermal injection at pure (100%) and diluted 50%, 25%, 12.5%, 6.25% and 3.125% in olive oil: No necrosis at any dose
- topical under 24h occlussive dressing at pure (100%) and diluted 50%, 25% and 12.5% in olive oil: No cutaneous reaction
Pre-test in 3 female guinea pigs:
After induction by intradermal injections with olive oil and by topical application with paraffin oil, and a 18-day rest phase, the challenge phase under occlusive dressing for 24 hours consisted in a single topical application of the test product at the following concentrations: pure (100%) and diluted at 50%, 25% and 12.5% in paraffin oil: no cutaenous reaction

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and topical, respectively)
- Exposure period: intradermal on day 0, topical on day 7
- Test group (10 females):
Intradermal induction on day 0:
a) 2 intradermal injections of the product pure (100%)
b) 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50 % in in a physiological saline solution
c) 2 intradermal injections of a mixture with equal volumes - Freund’s Complete Adjuvant at 50% and the product pure (100%)

Topical induction on day 7:
On the same zone, with the product at 100%, 24 hours after brushing with 0.5 mL of a solution of Sodium lauryl sulfate at 10%.

- Control group: 5 females, negative controls, no induction treatment

- Site: intradermal and topical induction on the same zone, anatomical region not stated
- Frequency of applications: 2 intradermal injections per induction substance [three substances as detailed above under a), b), and c)] and 1 topical application
- Duration: Duration and dressing of topical induction not stated
- Concentrations: intradermal 100% and 50%, topical 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: on day 27
- Exposure period: 24 h
- Test groups: 10 females
- Control group: 5 females
- Site: not stated
- Concentrations: 50% and 100% of test material applied to each animal
- Evaluation (hr after challenge): 24, 48 and 72 hours after the challenge phase

Challenge controls:

5 animals; the control group is actually a challenge control

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole and Neomycin sulfate

Positive control results:

>30% positive responses at testings conducted with: 50% 2-mercaptobenzothiazole in May 2004, 75% Neomycin sulfate in Mar 2003, and 75% Neomycin sulfate in Jan 2002.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

3

Total no. in group:

5

Clinical observations:

Score 1 erythema

Remarks on result:

other: 60%

Remarks:

of tested animals

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

Score 2 erythema

Remarks on result:

other: 20%

Remarks:

of tested animals

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

negative control

Dose level:

100%

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

Score 1 erythema

Remarks on result:

other: 20%

Remarks:

of tested animals

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

Three score 1 erythema and one score 2 erythema

Remarks on result:

other: 40%

Remarks:

of tested animals

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

Score 1 erythema

Remarks on result:

other: 40%

Remarks:

of tested animals

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

other: testings done on 18 May 2004 with 2-Mercaptobenzothiazole

Hours after challenge:

24

Group:

positive control

Dose level:

50%

No. with + reactions:

9

Total no. in group:

9

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

other: testings done on 18 May 2004 with 2-Mercaptobenzothiazole

Hours after challenge:

48

Group:

positive control

Dose level:

50%

No. with + reactions:

9

Total no. in group:

9

Remarks on result:

positive indication of skin sensitisation

No of Animals	M.N.I.C. (100%)						½		M.N.I.C. (50%)
	24 hours		48 hours		72 hours		24 hours		48 hours		72 hours
NEGATIVE CONTROL GROUP	Er	Oe	Er	Oe	Er	Oe	Er	Oe	Er	Oe	Er	Oe
(Vehicle)
N° C   0427        F	1	0	0	0	0	0	1	0	0	0	0	0
N° C   0428        F	1	0	2	0	1	0	1	0	1	0	0	0
N° C   0429        F	1	0	0	0	0	0	1	0	1	0	0	0
N° C   0430        F	0	0	0	0	0	0	0	0	0	0	0	0
N° C   0431        F	0	0	0	0	0	0	0	0	0	0	0	0
TREATED GROUP (Test product)	Er	Oe	Er	Oe	Er	Oe	Er	Oe	Er	Oe	Er	Oe
N° C   0442        F	0	0	0	0	0	0	1	0	0	0	0	0
N° C   0443        F	0	0	0	0	0	0	0	0	0	0	0	0
N° C   0444        F	0	0	0	0	0	0	0	0	0	0	0	0
N° C   0445        F	0	0	0	0	0	0	0	0	0	0	0	0
N° C   0446        F	1	0	1	0	0	0	1	0	1	0	0	0
N° C   0447        F	0	0	0	0	0	0	0	0	0	0	0	0
N° C   0448        F	0	0	0	0	0	0	1	0	1	0	0	0
N° C   0449        F	1	0	1	0	0	0	1	0	1	0	0	0
N° C   0450        F	1	0	1	0	0	0	1	0	1	0	0	0
N° C   0451        F	2	0	1	0	0	0	2	0	1	0	0	0

No mortality occured during the study. No clinical abnormalities were detected in body weight records.

A discrete to moderate erythema was recorded after challenge at 100%:

Test group: 40% (4/10) at 24h, 40% (4/10) at 48h, 0% (0/10) at 72h after the challenge phase.

Control: 60% (3/5) at 24 h, 20% (1/5) at 48 h, 20% (1/5) at 72h after the challenge phase.

The reactions observed in the control animals were judged to be skin irritation. Thus,as skin irritation was observed in the control animals, only reactions in the test group animals that exceeded the most severe reactions seen in the control group animals were attributed to skin sensitization.

Therefore, a sensitization reaction was recorded in 10% of the animals 24 hours after the challenge phase, on the area challenged with the test item at 100%. No sensitization reaction was noted 48 and 72 hours after the challenge phase, on the area challenged with the test item at 100%.

.

 

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The test item did not induce a significant sensitisation reaction when administered to the skin of albino guinea pigs after induction by intradermal injection and topical application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

A Guinea pig maximisation GLP study was performed with Fatty acids, coco, esters with 1,3-butanediol (CAS 73138-39-3) according to OECD Guideline 406 (key, 2004). No skin reactions were found in pre-tests with the undiluted test substance topically administered to the guinea pig skin for 24 hours under occlusive dressing. Ten test and 5 control Dunkin-Hartley guinea pigs were induced intradermally with undiluted test substance with and without Freud's complete adjuvant. On Day 7, an epicutaneous induction treatment with the 100% pure test substance was performed after pre-treatment with 10% SDS.

On Day 27, the challenge treatment was performed by topical application of the test substance at 100% and 50% (anatomical sites not reported) to all animals for 24 h, under occlusive conditions. Skin reactions were evaluated 24, 48, and 72 h after the challenge phase. At the skin sites challenged with 100% test substance, erythema of scores 1-2 was seen in 60%, 20%, and 20% of the control animals at 24, 48, and 72 hours after challenge. At the same time points erythema of scores 1-2 was seen in 40%, 40%, and 0% of the tested animals. In non-concurrent positive control testings with 2-mercaptobenzothiazole 100% of tested animals were positive for skin reactions, confirming the reliability of the assay. As irritation was observed in the control group animals, only reactions in the test group animals that exceeded the most severe reactions seen in the control group animals were attributed to skin sensitization (score 2). Therefore, a sensitization reaction was noted in 10% of the animals 24 hours after the challenge phase, on the area challenged with the test item at 100%. No sensitization reaction was noted 48 and 72 hours after the challenge phase, on the area challenged with the test item at 100%.

The test item did not induce a significant sensitisation reaction (i.e. reaction < 30%) when administered to the skin of albino guinea pigs after induction of the sensitisation by intradermal injection and topical application. Based on the results, the test substance had no sensitising effect in guinea pigs under the experimental conditions.

Overall conclusion for skin sensitisation

No skin sensitising potential was seen in an experimental study in guinea pigs performed with Fatty acids, coco, esters with 1,3-butanediol (CAS 73138-39-3).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.