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acute toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
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 toxicity study with rats (LD50 >3000 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 mode of actions or toxicity effects. Toxicokinetic behavior of the constituents of the target substance is expected to be essentially the same as that of the source substance. Based on the results of the oral 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 of the category members with shorter alkyl rests and theoretically higher absorption rates (due to the increased water solubility and decreased molecular weights favouring absorption) is higher, 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 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:
> 2.3 mg/L air (nominal)
Exp. duration:
4 h
No animals died following exposure to the test article.
Clinical signs:
other: Diarrhea was noted in one rat following exposure. All remaining rats appeared normal.
Body weight:
All test rats were weighed immediately prior to exposure. Body weights were not recorded following the observation period for comparison.
Gross pathology:
Gross necropsy findings for nine rats were within normal limits. The remaining rat had red foci throughout the liver.
Other findings:
Tan livers and kidneys were observed at necropsy, however, these were not deemed to be treatment related.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Under the conditions of this study, the test material did not produce significant toxicity at the nominal concentration of 2.3 mg/l in male or female Sprague Dawley rats.
Executive summary:

In an acute inhalation toxicity study similar to OECD guideline 403 (no GLP conditions), male and female rats were exposed to test substance at a nominal concentration of 2.3 mg/l (vapour) under continuous air flow conditions for 4 h. The LC50 is >2.3 mg/l. Diarrhea was noted in one animal, all other animals appeared normal. Based on the results of this study, the test substance would be unclassifiable in accordance with the classification system of GHS. The LC50 only eliminates Category 1 or 2 classification.This toxicity study is classified as acceptable and satisfies the guideline requirement for acute inhalation toxicity in rats.