Zinc, O,O-mixed (iso-Bu), (iso-Pr), (pentyl) phosphorodithioate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to 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 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

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

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

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Doses:

1.04, 2.36, 3.68, and 5.0 g/kg

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 080 mg/kg bw

Based on:

not specified

95% CL:

>= 2 570 - <= 3 700

Mortality:

No deaths occurred in the 1.04 g/kg dose group. One male died in the 2.36 g/kg dose group on day two. Four males and four females died in the 3.68 g/kg dose group between days 2 and 3. There were no surviving rats in the 5.0 g/kg dose group by day two.

Clinical signs:

other: other: other: Lethargy, diarrhea, ptosis, and brown staining at the anogenital area were observed in all dose groups and cleared within the first week at the 2 lowest doses. Ataxia was also noted in the higher dose groups and signs generally persisted to

Gross pathology:

All surviving animals were normal at necropsy. The animals which died during the test were observed to have lung, heart, and gastrointestinal abnormalities.

Other findings:

No other findings recorded.

Any other information on results incl. tables

All of the 5.0 g/kg animals died during the first two days of study. Eight of ten rats treated at 3.68 g/kg died during days 2 through 3. One male at the 2.36 g/kg dose level died on day 2. No deaths occurred at the 1.0 g/kg dose level. Lethargy, diarrhea, ptosis, and brown staining around the anogenital region were noted in all groups. These findings were no longer evident in the two lowest groups within the first week. Body weight changes were within expected ranges for the two lowest dose groups. Lung, heart, and gastrointestinal abnormalities were common necropsy findings for the animals that died.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as an acute toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

The test article, when administered as received to male and female Wistar rats, had an acute oral LD50 of 3.08 g/kg.

Executive summary:

In an acute oral toxicity study similar to OECD Guideline 401 in complince with GLP, male and female Wistar rats were exposed to test substance at doses of 1.04, 2.36, 3.68, and 5.0 g/kg. The oral LD50 is 3.08 g/kg. Sublethal effects of lethargy, diarrhea, ptosis, and brown staining at the anogenital area were observed in all dose groups. Necropsy observations included heart, lung and gastrointestinal abnormalities. Based on the results of this study, the test substance would not be classified in accordance with the CLP. This toxicity study is classified as acceptable and satisfies the guideline requirement for acute oral toxicity in rats.