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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
Please refer also to the read-across statement attached in section 13

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The target and the source substances are structurally similar substances that share the common organometallic core structure consisting of a central zinc metal bonded to four alkyldithiophosphate esters (ligands) by coordinate covalent bonds -Zn[(S2P(OR)2]2. Structural variations between the target and the source substances are related only to the alkyl (R) groups of the alkyldithiophosphate ligands. The substances in this category give thus rise to an (identical) common compound Phosphorodithioic acid moiety that can be released by the breakage of ester bonds and dissociation from the Zinc complex to which the organism would be exposed if the target substance was tested in the toxicity studies. Exposure to the parent compounds (non-transformed constituents) and to the counter alkyl alcohols, possibly released by hydrolysis of P-O bonds – non-common compounds – would not influence the prediction of the (eco)toxicological properties because they are considered to have the same biological targets and to cause the same type of effects through a common underlying mechanism due to the same functional groups (zinc cation, phosphorodithioic cation and aliphatic alcohol anionic moieties). The impurities of the target and the source substances are not expected to impact the prediction because they are identical or, if slightly structural different, belong to the same class of compounds with the same functional groups and their percentages are very low.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
The source substances were non-sensitising in skin sensitisation studies.
Since the main constituents of the target substance are structurally similar to the constituents of the source substances with the same functional groups and the alkyl chain lengths of phosphoroditioate moieties are in the range of the established ZDDP category (C3-C12), the same mode of toxicological action is expected for the target and the source substances. The constituents of the target substance do not possess functional groups associated with other deviating modes of action or toxicity effects from the source substances. Toxicokinetic behavior of the constituents of the target substance is expected to be essentially the same as that of the source substance. Thus, it is not likely that the structurally dissimilar alerts i.e. alkyl chain rests of the target substance would result in protein binding leading to hypersensitivity reactions. Therefore, a skin sensitisation of the target substance is not likely. The impurities of the target substance are considered not to contribute to sensitisation potential because they are also structurally similar to the impurities of the source substances and consist of substances of simple structure without specific mode of action and do not contain functional groups leading to protein binding and subsequently to a hapten formation and eliciting skin sensitisation.
Therefore, it is predicted that the target substance would not possess skin sensitisation potential if it was tested in a skin sensitisation study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Buehler test already available

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc, O,O-mixed (iso-Bu), (iso-Pr), (pentyl) phosphorodithioate
EC Number:
820-225-5
Cas Number:
101747-77-7
Molecular formula:
C12-20H28-44O4P2S4Zn
IUPAC Name:
Zinc, O,O-mixed (iso-Bu), (iso-Pr), (pentyl) phosphorodithioate
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig

Study design: in vivo (non-LLNA)

Induction
Concentration / amount:
12.5%

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3 mL 12.5 %
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3 mL 12.5 %
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 mL 12.5 %
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 mL 12.5 %
No. with + reactions:
0
Total no. in group:
10
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Erythemata, oedemata or other signs of allergic reactions of the animals could not be noted during the examination of effects to the challenge exposure.

Applicant's summary and conclusion

Interpretation of results:
other: not classified as a skin sensitiser according to the CLP Regulation (EC) No.1272/2008
Conclusions:
The substance is not sensitising to skin. The test substance does not meet the criteria for classification.
Executive summary:














In a GLP-compliant delayed contact hypersensitivity study in Guinea pigs (Buehler technique) according to OECD Guideline 406, 10 Pirbright White Guinea pigs were induced with 12.5 % w/v test substance. Erythema, edema or other signs of allergic reactions were not noted in any animal following challenge exposure. Based on these results the test substance does not appear to be a sensitiser in the guinea pig.















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