Undec-10-enal

Endpoint summary

Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on guinea pigs and humans for test chemical and its structurally similar read across chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data. Based on the available data for the target and supporting studies, it can be concluded that the test chemical is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

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

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: as mentioned below

Principles of method if other than guideline:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical

GLP compliance:

not specified

Type of study:

open epicutaneous 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:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

- Weight at study initiation: 300-450g

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:1%
Amount: 0.1ml

Day(s)/duration:

3 weeks (0-21 days)

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:1%
Amount: 0.025ml

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

6–8 male and female guinea pigs

Details on study design:

RANGE FINDING TESTS: The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, a single application of 0.025 ml of each test concentration (e.g, 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of preliminary study, the maximal non-irritating concentration selected was 1%. Thus the sensitization test was conducted at a dose of 1% of test chemical.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group:3 guinea pigs
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 1% in vehicle.
Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 6-8 guinea pigs
- Control group: 3 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:1%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

Challenge controls:

The 10 controls were either left untreated or treated with 0.1 ml aliquot of the vehicle for 21 days

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

1% (0.025ml)

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

No signs of dermal sensitization reactions were observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No signs of dermal sensitization reactions were observed.

Interpretation of results:

other: Not sensitizing

Conclusions:

The test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 1% in an Open Epicutaneous Test (OET).

Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical. The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, a single application of 0.025 ml of each test concentration (e.g, 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of preliminary study, the maximal non-irritating concentration selected was 1%. Thus the sensitization test was conducted at a dose of 1% of test chemical.

On day 1 during induction, 0.1 ml of test chemical was applied at concentrations of 1% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 1%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 1% in an Open Epicutaneous Test (OET).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies has been investigated for the test chemical to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments performed on guinea pigs and humans for test chemical and its structurally similar read across chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below;

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical. The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, a single application of 0.025 ml of each test concentration (e.g, 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of preliminary study, the maximal non-irritating concentration selected was 1%. Thus the sensitization test was conducted at a dose of 1% of test chemical.On day 1 during induction, 0.1 ml of test chemical was applied at concentrations of 1% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 1%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 1% in an Open Epicutaneous Test (OET).

 

AHuman maximization test was carried out in 25 volunteers to determine skin sensitization potential caused by the chemical. Each subject was treated with 1% of test chemical in petrolatum dermally and later observed for any signs of contact allergy. None of the volunteer showed any signs of contact sensitization. Hence the test chemical wasconsidered to be not sensitizing to theskin of human volunteers.

 

According to Danish QSAR database, skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, no Allergic Contact Dermatitis effects were observed when test chemical was exposed to human and guinea pig skin. Hence, the test chemical can be considered as not sensitizing to skin.

 

In next study, skin sensitizing potential of the test chemical was assessed by using the Mouse Local Lymphnode Assay.The LLNA was conducted on groups of CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute. An SI was calculated for each chemical group as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer, if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3) .The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value. The calculated stimulation indices at tested concentrations 5, 10, 25, 50 and 75% were 1.7, 5.3, 7.5, 8.7, 8.8and 6.8 respectively. Also the EC3 value of test chemical was calculated to be 6.8%. Based on the EC3 values, the test chemical was considered to be a moderate skin sensitizer.

 

The results of Non-LLNA studies were supported by Draize test conducted in Himalayan white-spotted guinea pigs (male and female) to determine the skin sensitization potential of the structurally similar read across chemical. In this test, the 6-8 guinea pigs received a dose of 0.05 ml of a 0.1 % solution of the chemical tested in isotonic saline intradermally on day 0 and further doses of 0.1 ml each were injected on 9 alternate days (total dose = 0.95 mg). The treated animals and untreated controls were challenged intradermally with 0.05 ml of a 0.1 per cent solution on days 35 and 49. The evaluation criterion was the mean diameter of the popular reactions. None of the treated animals showed positive skin reactions. Hence, the test chemical was considered to be not sensitizing to the skin of Himalayan white-spotted guinea pigs.

 

The overall results were further supported by another Human maximization test carried out in 25 volunteers for read across chemical. About 3% test chemical in petrolatum was applied to the skin of 25 human volunteers and later observed for signs of contact allergy. None of the volunteers showed any signs of contact sensitization. Hence the test chemical was considered to be not sensitizing to the skin of human volunteers.

Even though the LLNA study for the test chemical claims that there is a possibility of test chemical to cause moderate skin sensitization, but it is strongly negated by the results of the Non-LLNA studies performed on humans and Guinea pigs for the test chemicals and its structurally similar read across substances.

All these studies lead to a conclusion that Test chemical is indeed not sensitizing to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “Not Classified”.