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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

other: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline study; use of non-standard vehicle for dosing

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 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

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts

EC Number:

283-392-8

EC Name:

Phosphorodithioic acid, mixed O,O-bis(1,3-dimethylbutyl and iso-Pr) esters, zinc salts

Cas Number:

84605-29-8

IUPAC Name:

zinc bis[O-(1,3-dimethylbutyl) O-isopropyl dithiophosphate]

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not specified
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160 to 200 g (male), 140-180 g (female)
- Fasting period before study: not specifeid
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): not specified

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 10 % aqueous dispersion of gum Arabic

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal zone
- % coverage: not specified
- Type of wrap if used: aluminum foil fastened by a bandaid

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with warm water
- Time after start of exposure: 25 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg
- Concentration (if solution): 50.04 g/100mL
- Constant volume or concentration used: yes
- For solids, paste formed: not specified

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 ml/kg
- Concentration (if solution): not specified
- Lot/batch no. (if required): not specified
- Purity: not specified

Duration of exposure:

25 hours

Doses:

0 and 2002 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 7, and 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights

Statistics:

not specified

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 002 mg/kg bw

Mortality:

0 mg/kg: 0/10 dead
2002 mg/kg: 0/10 dead

Clinical signs:

other: other: other: Prostration in one animal. No other behavioral anomalies. Desquamation of the skin noted on test day 11.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as toxic via dermal route according to the CLP Regulation (EC)No.1272/2008

Remarks:

Based on the low level of toxicity and no mortality observed at 2002 mg/kg, material is not classified for acute dermal toxicity.

Conclusions:

The rat dermal LD50 is greater than 2002 mg/kg in male rabbits.

Executive summary:

This substance does not show adverse toxicity effects via the dermal route of exposure in animals when tested in accordance with OECD Guideline 402 and GLP. The rat dermal LD50 is greater than 2002 mg/kg in male rabbits. Prostration in one animal, and desquamation of the skin noted on test day 11 were observed. No specific organ toxicity is evident.