Registration Dossier

Administrative data

Description of key information

Skin sensitisation: not sensitising based on a read across from Zenolide which was tested in a Buehler test (OECD TG 406).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across information.
Justification for type of information:
This information is retrieved from Zenolide. The read across rationale is presented in the Skin sensitisation Endpoint summary and the accompanying files are also attached there.
Reason / purpose:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
32
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Reading:
other:
Group:
positive control
Remarks on result:
other: check report
Reading:
other:
Group:
negative control
Remarks on result:
other: check report
Interpretation of results:
other: Not a skin sensitiser
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
Oenanthic ether is not a skin sensitiser based on read across from Zenolide,which was tested in an OECD TG 406.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
The Buehler test is performed before the REACH regulation of 2016 came into force.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD TG 406 but not under GLP and therefore a reliability 2 is assigned.
Justification for type of information:
The Buehler test is performed before the REACH regulation of 2016 came into force. The Buehler test is considered sufficiently reliable because 100% substance has been used for induction and challenge.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no control group used
GLP compliance:
no
Type of study:
Buehler test
Justification for non-LLNA method:
The study was performed before the LLNA method was an OECD TG method.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
Weight of animals 300g; Temp. 21°C ± 2°C; Humidity 45 - 55%
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20; one dose was used
Details on study design:
0.5ml of the pure substance is applied to a plaster of 19*25 mm. This was then fixed with an Elastoplaster on the left site of the animal. This area was shaved. The animal was then fixed in a holder for 6 hours. This treatment was performe twice a week for three weeks
Challenge controls:
All animals were retreated on both sides 14 days after the last treatment. Plaster was removed after 6 hours and after another 2 hours the assessment was made.
Positive control substance(s):
no
Positive control results:
There are no positive or negative controls presented in the study.
Key result
Reading:
1st reading
Hours after challenge:
32
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Key result
Reading:
other: check report
Group:
positive control
Remarks on result:
not measured/tested
Key result
Reading:
other: check report
Group:
negative control
Remarks on result:
other: check report

Animals showed a normal clinical appearance throughout the study. No contact hypersensitivity was observed. Skin reaction and oedema formation was observed. The redness of the skin was measured with a refractometer and was assesed with Draize score. Results: Draize score 0 - 1 for all 20 animals with remark: hair removal reaction. Results refractometer shows average values of 135 (left) and 137 (right).

Interpretation of results:
other: Not a skin sensitiser
Remarks:
according to EU CLP (EC No. 1272/2008 and its amendments).
Conclusions:
Under the conditions of this study the test substance is not sensitizing.
Executive summary:

In a skin sensitisation study, performed similar to OECD guideline 406, twenty guinea pigs were dosed with 0.5 mL of the substance in an Elastoplaster on the left site of the animal for six hours. The treatment was repeated twice a week for three weeks. No positive control group was included in the study. Fourteen days after topical induction, challenge dosing for detection of sensitisation was performed on both left and right sides of the animals. For challenge undiluted test substance was used. The redness of the skin was measured with a refractometer and was assessed according to the Draize score. There were no deaths or clinical findings. Draize scores from 0 to 1 were observed for all 20 animals. A hair removal reaction was noted. There were no sensitisation differences between left and right side of the animals detected. No contact hypersensitivity was observed in this study.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation is assessed based on read-across from Zenolide to Oenanthic ether. The executive summary of Zenolide's Buehler test is presented first, followed by the read-across rationale.

Zenolide and its skin sensitisation potential

In a skin sensitisation study, a Buehler test, performed similar to OECD guideline 406, twenty guinea pigs were dosed with 0.5 mL of pure Zenolide in an Elastoplaster on the left site of the animal for six hours. The treatment was repeated twice a week for three weeks. No positive control group was included in the study. Fourteen days after topical induction, challenge dosing for detection of sensitisation was performed on both left and right sides of the animals. For challenge undiluted Zenolide was used. The redness of the skin was measured with a refractometer and was assessed according to the Draize score. There were no deaths or clinical findings. Draize scores from 0 to 1 were observed for all 20 animals. A hair removal reaction was noted. There were no sensitisation differences between left and right side of the animals detected. No contact hypersensitivity was observed in this study.

The skin sensitising properties of Oenanthic ether using read across from Zenolide (CAS 54982-83-1)

 

Introduction and hypothesis for the analogue approach

Oenanthic ether consists of 3 main constituents and a number of impurities. All are ethyl esters, despite the name ether, of long chain carboxylic acids. The major constituent has a C12 chain, the two minor ones have C14 and C16 saturated carbon chain. For this substance there are no experimental skin sensitisation data.

In accordance with Article 13 of REACH, lacking information can be generated by other means i.e. applying alternative methods such as QSARs, grouping and read-across. For assessing the skin sensitizing properties of Oenanthic ether, the analogue approach is selected because for the closely related analogue Zenolide sensitisation information is available which can be used to read across.

Hypothesis: Oenanthic Ether has the same skin sensitising properties compared to Zenolide. The structural differences are not expected to affect the skin sensitising properties.

Available information: The source chemical Zenolide has been tested in a skin sensitisation study, a Buehler test, performed similar to OECD guideline 406. Twenty guinea pigs were dosed with 0.5 mL of the substance in an Elastoplaster on the left site of the animal for six hours. The treatment was repeated twice a week for three weeks. A positive control group was not included in the study and is not needed. Fourteen days after topical induction, challenge dosing for detection of sensitisation was performed on both left and right sides of the animals. For challenge undiluted test substance was used. The redness of the skin was measured with a refractometer and was assessed according to the Draize score. There were no deaths or clinical findings. Draize scores from 0 to 1 were observed for all 20 animals. A hair removal reaction was noted. There were no sensitisation differences between left and right side of the animals detected. No contact hypersensitivity was observed in this study and therefore Zenolide is not a skin sensitiser.This Buehler test is considered sufficiently reliable because up to 100% substance has been used for induction and challenge.

Target chemical and source chemicals

Chemical structures of the target chemical and the source chemical(s) are shown in the data matrix, including physico-chemical properties and available toxicologicalinformation. Furthermore, a full list of constituents of Oenanthic ether, including information relevant for read-across, is given in the data matrix.

Purity / Impurities

The purity and unidentified impurities of the target chemical and source chemical are not expected to influence the potential for skin sensitisation.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation. The reasoning below fulfils this documentation.

Analogue selection: For Oenanthic etherZenolide was considered an appropriate analogue because Zenolide has a similar fatty acid type of acetic ester as Oenanthic ether and for Zenolide skin sensitisation information was available. 

Structural similarities and differences:All constituents of Oenanthic ether and Zenolide contain ethyl esters and a long alkane chain (C8-C18 and C12, respectively) and therefore have a similar backbone and functional group: i.e. esters of long chain carboxylic acids. The difference is that all constituents of Oenanthic ether have linear alkyl chains, whereas Zenolide has a cyclic aliphatic alkyl chain, connected by Ethylene glycol. In view of this double ester this site is likely more electrophilic.

Toxico-kinetics: The dermal availability of Oenanthic ether is very similar or may be slightly less compared to Zenolide because the former has a several constituents with higher molecular weights and log Kow outside the favourable dermal absorption range.

Skin sensitisation reactivity profile:The reactive site of Oenanthic Ether and Zenolide is the ester bond which has only a non-branched alkyl group in its vicinity and therefore is expected to react very similar. If anything Zenolide is slightly more reactive because it has a double ester in the vicinity of each other (OECD Toolbox, 4.2). Therefore the prediction is ‘conservative’.

Uncertainty of the prediction: There are no other remaining uncertainties not already addressed above. In addition, the OECD Toolbox profiler (4.2) does not indicate protein binding for Oenanthic ether.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the data matrix below.

Conclusions for hazard and risk assessment

For Oenanthic ether no skin sensitisation information was available. Zenolide and its skin sensitisation information can be used for read across. When using read across, the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. This latter documentation is presented here in the current document. For Zenolide a well conducted Buehler test is available (OECDTG 406, Rel. 2, tested up to 100%) resulting in absence of skin sensitisation. Therefore also Oenanthic ether is not a skin sensitiser.

Final conclusion on hazard and risk assessment:Oenanthic ether is not a skin sensitiser.

 

Data matrix to support the read across to Oenanthic ether from Zenolide for skin sensitisation

Chemical names for

 

Oenanthic ether#

ethyl octanoate (C8*)

ethyl decanoate (C10*)

ethyl dodecanoate (C12*)

ethyl tetra-decanoate (C14*)

ethyl hexa-decanoate (C16*)

ethyl octa-decanoate (C18*)

ethyl (9Z)-octadec-9-enoate (C18*)

ethyl (9Z,12Z)‐ octa-deca‐,12‐di enoate (C18*)

Zenolide

(‘C12’)

Target

 

 

 

 

 

 

 

 

Source

CAS#

106-32-1

110-38-3

106-33-2

124-06-1

628-97-7

111-61-5

544-35-4

111-62-6

5982-83-1

Structure

% in product

<10

<10

35-55

15-30

5-15

<10

<10

<10

 

EC No.

945-734-0#

 

 

 

 

 

 

 

 

259-423-6

Registration 2018

 

 

 

 

 

 

 

 

Registered

Vp (Pa)

0.12 meas)#

 31.4

(est.)

 5.70

(est.)

 1.17

(est.)

 0.34

(est.)

0.036

(est.)

0.0084

(est.)

 0.0081

(est.)

 0.0067

(est.)

0.028

 (exp.)

WS (mg/L)

1.6 meas)#

 45.6

(est.)

 4.8

(est.)

 0.41

(est.)

 0.037

(est.)

 0.0037

(est.)

0.0004

(est.)

 0.0006

(est.)

 0.0009

(est.)

75

 (exp.)

Log Kow

4.6 meas)#

 3.8

(est.)

 4.8

(est.)

 5.8

(est.)

 6.8

(est.)

 7.7

(est.)

 8.4

(est.)

 8.5

(est.)

 8.3

(est.)

3.65

(exp.)

Human health

 

 

 

 

 

 

 

 

 

Skin sensitisation

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (Read across)

Negative (OECD TG 406, Buehler, using 100%)

*The C’s are related to the chain length not the overall number of Cs (as would be presented in the Empirical formula); (est.) = estimated using EpiSuite; (exp.) = experimental;#In this column the values are for Oenanthic ether as such.

 

Justification for classification or non-classification

Based on the results, the substance does not need to be classified for skin sensitisation according to EU CLP (EC No. 1272/2008 and its amendments).