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Categories

Category name:
Phosphorodithioic acid, mixed O,O-bis(alkyl) esters, zinc salts

Justifications and discussions

Category rationale:
REPORTING FORMAT FOR THE CATEGORY APPROACH
Please refer also to the read-across statement attached in section 13

1. CATEGORY HYPOTHESIS
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 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 JUSTIFICATION
The source substances CAS 68457-79-4, CAS 84605-29-8 and CAS 4259-15-8 are members of ZDDP chemical category but the target substance can be added to this category because their alkyl rests are in the range of the chain lengths defined for this category. All substances in the ZDDP category “consist of alkyl (C3-C12) or alkaryl (C12 alkylphenol) substituted phosphorodithioic acid structures complexed with zinc” (HPV, 2005). “The physicochemical, environmental toxicity and fate, and (eco)toxicological properties of the zinc dialkyldithiophosphate category members in highly refined lubricant base oils are similar and follow a regular, predictable pattern” (HPV, 2005).

As result of high structural similarity, the chemical reactivity and thus environmental fate and (eco)toxicity of the target and the source substances can be expected to be very similar. Structural dissimilarities of the target substance (different structures and lengths of the alkyl groups of alkyldithiophosphate ligands) are considered not to influence the read-across validity because there are no structural alerts associated with specific toxicity effects other than those present in the source substances.


3. APPLICABILITY DOMAIN OF THE CATEGORY
The source and the target substances are structurally similar substances with only difference in the chain lengths and branching of alkyl rests attached through ester bonds to phosphorodithioic acid moiety complexed with zinc.
The ester group presents in each of the source and the target substances, and therefore they exhibit similar biological activities. The substances have comparable molecular weight, Log Kow, they are all water soluble to a certain extent and have very low vapor pressure while considering their varying substituents. Their toxicokinetic behavior and ADME parameters are expected to be essentially very similar. The similarity of the physicochemical properties of these substances parallels their structural similarity. Non-random patterns were observed for the toxicological effects of the source substances and other ZDDP category members (e.g. no biodegradation, low bioaccumulation potential, stability to hydrolysis, low levels of acute toxicity effect, irritation potential, absence of mutagenic activity, consistent trend of change in ecotoxicity effect, similar findings in the repeated dose toxicity studies etc.). These common behaviors and consistent trends suggest a common mechanism/mode of action, with little influence from the length of carbon chain. These facts further supported read-across between the source and the target substances.