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Acute Toxicity: dermal

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acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer also to the read-across statement attached in section 13

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.

The acute toxicity potential of the ZDDP category members is reported to be low (HPV, 2005). The source substances were practically non-toxic in the acute oral and dermal toxicity study with rats (LD50 >2000 mg/kg bw).
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 modes of action or toxicity effects. Toxicokinetic behaviour of the constituents of the target substance is expected to be essentially the same as that of the source substances. Based on the results of the acute toxicity studies with the source substances and other ZDDP category members it is evident that the structural dissimilarities – the chain lengths of the alkyl rests – did not result in different strength of the toxicity effects. Even if absorption through GI tract or skin of the category members may differ due to different molecular weight and water solubility, their intrinsic properties are essentially the same as the findings in the acute toxicity studies are very similar. The impurities of the target substance are considered not to contribute to the toxicity effects 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. Furthermore their amounts are very low. Therefore, it is predicted that the target substance would possess the same toxicity potential by acute oral and dermal exposure as the source substance.

Data source

Materials and methods

Test material

Chemical structure
Reference substance name:
Zinc, O,O-mixed (iso-Bu), (iso-Pr), (pentyl) phosphorodithioate
EC Number:
Cas Number:
Molecular formula:
Zinc, O,O-mixed (iso-Bu), (iso-Pr), (pentyl) phosphorodithioate
Test material form:

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 5 000 mg/kg bw
One animal with abraded skin died 13 days after dosing
Clinical signs:
other: Severe erythema and edema noted at 24 hours. By seven days treated sites were thick and escharotic.
Gross pathology:
Liver-like or necrotic-appearing areas of lung tissue observed in five rabbits. Further histology of the lungs revealed confluent bronchipnuemonia or chronic interstitial pneumonia. Two rabbits had small white liver abcesses that were determined to be of parasitic origin after histological examination.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Based on the low level of toxicity and no mortality observed at 2002 mg/kg, material is not classified for acute dermal toxicity.
The rat dermal LD50 is greater than 5000 mg/kg in male rabbits.
Executive summary:

This substance does not show any evidence of toxicity via the dermal route of exposure in animals when tested in accordance with OECD Guideline 402. The rat dermal LD50 is greater than 5000 mg/kg in male rabbits. Severe erythema and edema noted at 24 hours. Necrotic-appearing areas of lung tissue observed in five rabbits. Further histology of the lungs revealed confluent bronchopneumonia or chronic interstitial pneumonia.