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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
January 28, 2019 - February 01, 2019
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other:
Remarks:
Study was conducted in other Registrants laboratory as a preliminary experiment to determine the molecular confirmation under conditions that mimic the temperature and pH of the stomach.

Data source

Materials and methods

GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Two substances that comprise the zinc dialkyldithiophosphate (ZDDP) category were tested:
1. Phosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl) esters, zinc salts (EC 272-238-5; CAS 68
784-31-6)
2. Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (EC 224-235-5; CAS 4259-15-8)

Results and discussion

Any other information on results incl. tables

These results demonstrate that under the conditions and temperature of the stomach, the basic form of

ZDDP is quickly converted to the neutral form. The basic form was converted to neutral within 5 minutes

(secondary) or 15 minutes (primary – likely slower than primary due to higher starting amounts of basic).

The chromatograms of the results are included in the illustrations section.

Applicant's summary and conclusion

Conclusions:
These results demonstrate that, upon ingestion, ZDDPs will rapidly and completely convert from the basic form to the neutral form.
Executive summary:

A critical question about the ZDDP chemical category is whether the amount of basic vs. neutral ZDDP

will influence the toxicity and, hence, wether this is a variable that requires consideration in e.g., the

boundary composition for the category. These results demonstrate that, upon ingestion, ZDDPs will

rapidly and completely convert from the basic form to the neutral form. This information is critical to

developing the Intelligent Testing Strategy for the ZDDP category because it demonstrates that the

basic form of ZDDPs are not relevant from a toxicity perspective. Specifically, upon ingestion there is

transformation of all ZDDPs to the neutral form which becomes the common denominator.