Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The test item tetramethrin was tested for skin sensitisation potential in Guinea pigs using the Buehler test method (OECD Guideline No.406, EEC Method B.6). The animals were given three topical applications (induction) weekly for three weeks (viz., on days 1, 8 and 15 of the test) and one challenge application (viz., on day 29 of the test).

A quantity of 0.5 g of test item as a paste (which is equivalent to 100% concentration) in de-ionised water was transferred completely onto the cotton gauze (2 x 3 cm, 6 ply) and applied on to the prepared area of the left flank as a patch. An equivalent amount was used in the challenge applications at the posterior part of the untreated flank. Positive control group animals were treated similarly with 0.5 ml of 2-Mercaptobenzothiazole (2-MBT) at a concentration of 12% w/v in acetone.

The skin reaction was evaluated in the vehicle control and treatment group animals using the grading scale of Draize, 1959 for induction and the grading scale of Magnusson and Kligman for challenge application.

The challenge application site was evaluated at 24 and 48 hours after removal of the test patch. There was no skin reaction (erythema) observed in the test item treated animals. In the positive control group animals the skin sensitisation rate was 80% (8/10). The comparison of the skin reaction of the test item treated animals with those of the positive control animals showed that the test item did not cause skin sensitisation in the tested animals and hence, it is concluded that tetramethrin did not cause skin sensitisation in Guinea pigs using the Buehler Test method under the stated experimental conditions.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance is the racemic form of the target substance d-tetramethrin. Tetramethrin does consist of 50% d- and l-form, and both do exist as cis and trans isomers. Hence, the target substance does consist of d-cis-tetramethrin, d-trans-tetramethrin, l-cis-tetramethrin and l-trans-tetramethrin, whereas the target substance only contains the first two (i.e. d-cis-tetramethrin, d-trans-tetramethrin).
Both, the source as well as the target substance, do have a cis/trans ratio of approximately 1/4 and obviously do share same molecular formula and mass, functional groups and other properties. Thus, the source substance by definition does contain ~50% of the d-form and the l-form is not expected to be significantly different with respect to its toxic properties. Acute effects to skin and eyes as well as skin sensitisation has been assessed in GLP guideline toxicity studies to assess acute toxicity effects to skin and eyes. Accordingly, data do indicate that racemic tetramethrin and thus also d-tetramethrin is not affecting eyes and skin by irritation in rabbits, nor does it cause skin sensitizing properties in guinea pigs. Results of d-tetramethrin are not expected to significantly differ from the racemic mixture, considering that this contained the d-enantiomer as the main component.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The d-tetramethrin with a purity > 80 % does contain its corresponding l-form as an impurity in the range of < 7%, other impurities from the manufacturing process are individually below 1% (w/w) each. The source substance that has been tested was having a purity of approx. 98% as tetramethrin with a cis/trans ratio of 1/4 and a d-form/l-form ratio of ~50/50.
3. ANALOGUE APPROACH JUSTIFICATION
Source and Target substance do share identical structure and molecular weight, only differentiating by the fact that the source substance is a racemic mixture, whereas the target substance represents almost pure d-form. Thus, behaviour regarding skin and eye irritating effects as well as skin-sensitisation are not being affected significantly by stereochemistry, and being fully comparable, thus justifying using available data on rodent toxicity properties on the racemic form for read-across to the d-enantiomer.
4. DATA MATRIX
Composition comparison
D-tetramethrin (target) tetramethrin (source)
D-trans tetramethrin 70 - 80% 40 – 50%
D-cis tetramethrin 10 - 20% 7 – 11 %
L-trans tetramethrin 0 – 5% 35 – 40%
L-cis tetramethrin 0 – 2% 7 – 11%
Reason / purpose for cross-reference:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
7
Clinical observations:
no
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
7
Clinical observations:
no
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2-Mercaptobenzothiazole (2-MBT) at 12% w/v in acetone
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
none, besides sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
2-Mercaptobenzothiazole (2-MBT) at 12% w/v in acetone
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
none, besides sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The study showed that the test item racemic tetramethrin did not have any skin sensitisation potential when tested in Guinea pigs using the Buehler test method under the stated experimental conditions. Accordingly, also d-tetramethrin, being a major constituent therein, is not being considered sensitising to skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a skin sensitisation study following OECD 406, Buehler method, no positive reaction of guinea pigs to the challenge application was seen and thus, the substance is not subject to classification as a skin sensitiser according to CLP (Regulation EC No. 1272/200). Data on respiratory sensitisation are not available.