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EC number: 298-577-9
CAS number: 93819-94-4
EC 283-392-8 has not
been tested for repeat dose toxicity, however experimental data on
structurally related substances EC 270-608-0 (OECD 422) is available and
suitable for read-across. Justifications for read-across:
EC 283-392-8 and EC
270-608-0 are generically referred to as zinc dialkylthiophosphate
(ZDDP) which are produced under similar manufacturing procedures and
used in commerce as multi-functional anti-wear and anti-oxidation
inhibitor performance components in passenger motor oils, diesel engine
oils and industrial oils such as hydraulic lubricants.
EC 283-392-8 and EC
270-608-0 consist of alkyl substituted phosphorodithioic acid structures
complexed with zinc.
acid, mixed O,O-bis(1,3-dimethylbutyl and iso-propyl) esters, zinc
salts, referred to as “mixed isopropyl and 1,3-dimethylbutyl derivative”
acid, mixed O,O-bis(iso-butyl and pentyl) esters, zinc salts – (CAS 68457-79-4),
referred to as “mixed isobutyl and pentyl derivative”
These ZDDPs share
similar core structures - alcohol ester of dithiophosphate, specific
structural variations that relate to their alcohol group substituent are
the alkyl chain length and the degree of branching of the alcohol charge.
Fingerprint (ToxMatch Version 1.06 software) to model chemical
structures of the analogues showed comparable values for relevant
molecular descriptors (e.g., number of H bond acceptor atoms), and gave
a similarity index greater than 0.8 (values range from 0, no similarity
to 1, identical; peer reviewed literature indicates that values greater
than 0.6 are significantly similar); therefore chemical structures of
the analogues have determined to be sufficiently close for there to be a
reasonable expectation of similar toxicological effects.
physicochemical properties for each substance were listed in Table 1.
Table 1. Establishment
of similarity between the data donating substance and the data accepting
Water Sol (ppm)
Vapor Pressure (Pa at 25 oC)
C5, mixture of linear and branched
As shown in Table 1,
these two substances have the same molecular weight, similar Log Kow,
low vapor pressure, and both are water soluble. The similarity of the
physicochemical properties of these substances parallels their
Active Functional Groups:
The ester group
presents in each of the analogue members, and is expected to exhibit
similar biological activities. Non-random patterns were observed for the
toxicological effects (e.g. available data showed low levels of acute
toxicity effect, lacking of mutagenic effect in bacteria, consistent
trend of change in ecotoxicity effect, etc.), these common behaviors and
consistent trends suggest a common mechanism/mode of action, with little
influence from the length of carbon chain. These facts further supported
read-across between the analogue members.
and Adequacy for Read-across:
EC 270-608-0 was
evaluated with rats at doses as high as 160 mg/kg/day for up to 52
consecutive days in accordance with OECD 422. Substance-related toxicity
was limited to morbundity, adverse clinical signs, and epithelial
hyperplasia, hyperkeratosis, and inflammation of the stomach. The
parental NOAEL for systemic toxicity was 160 mg/kg/day.
Based on the
abovementioned justifications, results from EC 270-608-0 OECD 422 study
was determined to be adequateto
fulfill the purposes of this endpoint.Therefore,
NOAEL of 160 mg/kg/day for systemic toxicity was proposed for EC
283-392-8, and use of read-across will eliminate the need for new animal
testing while allow meeting the data requirements.
In a guideline combined repeated dose and reproduction / developmental
screening study (OECD 422) conducted according to Good Laboratory
Practices, WIL Research Labs (2010) evaluated the potential toxic
effects ofphosphorodithioic acid, mixed O,O-bis(iso-Bu and pentyl)
esters, zinc saltswhen administered to rats. This study was designed to
evaluate the toxic effects, including neurobehavioral effects, of the
test material to parental animals and to evaluate the potential to
effect male and female reproductive performance such as gonadal
function, mating behavior, conception, parturition, and early postnatal
development. The test material was administered orally by gavage once
daily to 3 groups of Crl:CD(SD) rats at levels of 10, 40 or 160
mg/kg/day. The low- and mid-dose groups each consisted of 10 rats/sex
and the high-dose group consisted of 15 rats/sex. A concurrent control
group of 15 rats/sex received the vehicle, mineral oil USP, on a
comparable regimen. Ten males/group selected for pairing were dosed for
14 days prior to mating through 1 day prior to euthanasia for a total of
28 doses. Ten females/group selected for pairing were dosed for 14 days
prior to mating through lactation day 3 for a total of 40-52 doses;
females that failed to deliver were dosed through the day prior to
euthanasia (post-mating day 25) for a total of 40 doses. The extra 5
males and 5 females in the control and high-dose groups were not used
for mating and were treated beginning on study day 0; following 28 doses
for the males and 40 doses for the females, these animals were assigned
to the post-treatment period and remained on study for a 14-day
Test item-related moribundity, clinical findings, and microscopic
findings in the non glandular portion of the stomach, characterized by
epithelial hyperplasia, hyperkeratosis, and inflammation, were observed
in the 160 mg/kg/day group. The injury to the nonglandular portion of
the stomach was localized and considered to be irritation from test item
portal-of-entry effects. Based on these results, the NOEL for
portal-of-entry effects was considered to be 40 mg/kg/day, and excluding
the histologic injury to the nonglandular stomach, the
no-observed-adverse-effect level (NOAEL) for systemic toxicity was
considered to be 160 mg/kg/day.
This result is deemed to be applicable to the Registration material EC
298 -577 -9.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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