Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
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
Severe gastrointestinal irritation was observed in oral repeated dose toxicity studies with several ZDDP category members (HPV, 2005). “Repeated dermal exposure to experimental animals resulted in moderate-to-severe dermal irritation, behavioral distress, body weight loss and emaciation, reduction in hematological parameters and adverse effects on male reproductive organs”. The source substances were also irritating to skin and severely irritating to eyes. Thus, it is evident that irritation is a primary hazard of this category.
Since the 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 that are in the range of the established ZDDP category (C3-C12), it is assumed to have the same reactivity to skin and eyes as the source substance.
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 those of the source substances. Due to the molecular weight, water solubility and logPow values, the target and the source substances are expected to react with the skin proteins to a similar degree. There is no evidence of increasing or decreasing irritating properties of the ZDDP category members that could be correlated with an increase or decrease in carbon chain length or molecular weight. Thus, an enhancement of irritation properties of the target substance is not likely. The impurities of the target substance are considered not to contribute to the irritation potential 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 and do not contain functional groups associated with irritation properties. Furthermore their amounts are very low. Therefore, it is predicted that the target substance would possess the same irritation potential to skin and eyes as the source substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Principles of method if other than guideline:
The source substance was assessed in an in vivo skin irritation study with 3 rabbits.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
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:
rabbit

Test system

Type of coverage:
occlusive
Duration of treatment / exposure:
4 hours

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: male
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
not fully reversible within: 2 days
Remarks on result:
other: male
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: females
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: male
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: male
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: female
Irritation parameter:
overall irritation score
Basis:
animal #1
Remarks on result:
not measured/tested
Irritation parameter:
overall irritation score
Basis:
animal #2
Remarks on result:
not measured/tested
Irritation parameter:
overall irritation score
Basis:
animal #3
Remarks on result:
not measured/tested
Irritant / corrosive response data:
After removing the occlusive bandage after a period of 4 h, the exposure area was washed and cleaned with water. In the following observation period dermal irritations of the exposure area in form of a very slight erythema could be observed.
Other effects:
Mortality: none of the rabbits died during the experiment.
Toxicological symptoms: During the observation period of 10 days none of the animals showed toxicological signs.
Behaviour: The reaction of the animals treated was quiet and watchful. The behaviour pattern was normal.
Body weight: The body weight of all animals had a normal physiological growth.

Applicant's summary and conclusion

Interpretation of results:
other: not classified as a skin irritant according to the CLP Regulation (EC) No.1272/2008
Conclusions:
The substance is not irritating to skin. The test substance does not meet the criteria for classification according to CLP Regulation.
Executive summary:

The source substance was assessed in an in vivo skin irritation study with 3 rabbits.


After removing the occlusive bandage after a period of 4 h, the exposure area was washed and cleaned with water. In the following observation period dermal irritations of the exposure area in form of a very slight erythema could be observed.


The substance is not irritating to skin. The test substance does not meet the criteria for classification according to CLP Regulation.