**EXTENDED HIGH PRODUCTION VOLUME (HPV)**

**CHEMICAL INITIATIVE**

**ADDENDUM**

**to**

**ZINC DIALKYLDITHIOPHOSPHATE CATEGORY**

**Prepared by**

**The Lubrizol Corporation**

**September 2007**

# INTRODUCTION

In 2005, the American Chemistry Council Petroleum Additives Panel
Health, Environmental, and Regulatory Task Group (HERTG) submitted a
final chemical category dossier for the Zinc Dialkyldithiophosphates to
the Environmental Protection Agency High Production Volume (HPV)
Chemical Challenge Program. Since that time, additional zinc
dialkyldithiophosphates have been identified through the 2002 TSCA IUR
as being HPV chemicals. This addendum describes the continuity of these
new HPV chemicals to the existing Zinc Dialkyldithiophosphate Category.

This addendum describes the following chemicals substances (idealized
structures are represented in Table 1):

-   Phosphorodithioic acid, mixed O, O-bis(2-ethylhexyl and isobutyl)
    esters, zinc salts -- CAS# 68909-93-3

-   Phosphorodithioic acid, mixed O, O-bis(2-ethylhexyl and isopropyl)
    esters, zinc salts -- CAS# 68442-22-8

It is important to note that the chemical entity described by CAS#
68909-93-3 is chemically identical to a HPV chemical addressed in the
Zinc Dialkyldithiophosphate Category dossier (attached in Appendix I)
with the name 'phosphorodithioic acid, mixed O-(2-ethylhexyl) O-isobutyl
ester, zinc salt' -- CAS# 26566-95-0 (structure is presented in Table
1). Since both CAS registry numbers describe the same chemical entity,
as previously described in the previous HPV submission, this addendum
will only address the physicochemical, environmental fate, aquatic
toxicity and health effects of the unique 2-ethylhexyl and isopropyl
derivative described by CAS# 68442-22-8.

**TABLE 1**

**CHEMICAL STRUCTURES and CAS NUMBERS OF ZINC DIALKYLDITHIOPHOSPHATES**

####### 

+---------------+------------------------------------------------------+
| **CAS         | **Chemical Structure**                               |
| Number**      |                                                      |
+===============+======================================================+
| 68909-93-3    | ![](media/image1.wmf)                                |
|               |                                                      |
| (chemically   |                                                      |
| equivalent to |                                                      |
| 26566-95-0    |                                                      |
| already       |                                                      |
| addressed     |                                                      |
| under the     |                                                      |
| existing Zinc |                                                      |
| Dialkyldi     |                                                      |
| thiophosphate |                                                      |
| HPV Category  |                                                      |
| dossier)      |                                                      |
+---------------+------------------------------------------------------+
| 68442-22-8    | ![](media/image2.wmf)                                |
+---------------+------------------------------------------------------+

####### 

A review of the public literature and confidential company data was
conducted on the physiochemical properties, mammalian toxicity endpoints
and environmental fate/effects for the zinc dialkyldithiophosphate
covered in this category addendum. Searches included the following
sources: EPA and ICCA HPV chemical data submissions, MEDLINE, BIOSIS,
CANCERLIT, CAPLUS, CHEMLIST, EMBASE, HSDB, RTECS, EMIC, and TOXLINE
databases; the TSCATS database for relevant unpublished studies on these
chemicals; and standard handbooks and databases (e.g., Sax, CRC Handbook
on Chemicals, IUCLID, Merck Index, and other references) for
physiochemical properties.

# GENERAL SUBSTANCE INFORMATION

Zinc dialkyldithiophosphates consist of a phosphorodithioic acid
structure with alkyl or alkaryl ester substituent groups. The alkyl
groups are saturated hydrocarbon chains that vary in length and in the
extent of branching. These substances are prepared by reacting
phosphorous pentasulfide (P~2~S~5~) with one or more primary or
secondary C~3~-C~10~ branched or linear alcohols to form the
phosphorodithioic acid ester. The dithiophosphoric acid ester is further
diluted with 10-15 wt-% highly refined lubricating base oil before it is
neutralized with zinc oxide. The oil acts as a solvent in the
neutralization reaction, manages the viscosity of the final product and
improves consistency. The zinc complex that is formed upon
neutralization is not a salt in the traditional sense, since the Zn-S
bond is more coordinate covalent in character than ionic. The acid
intermediates are typically neutralized on the same site where they are
manufactured. Zinc dialkyldithiophosphates are typically manufactured
and processed in contained systems and stored in closed vessels.
Automated processes (closed piping/pumping systems) are designed to
minimize exposure to product. At manufacturing facilities, proper
personal protective equipment and other containment measures are
employed to minimize worker exposure.

## Use and Exposure information

Zinc dialkyldithiophosphates are used to formulate finished lubricating
oils including all types of automotive and diesel engine crankcase,
industrial oils and hydraulic fluids. They are used as anti-wear
inhibitors to reduce wear in engines and hydraulic equipment parts, and
also act as antioxidants. Zinc dialkyldithiophosphates are generally
sold to finished oil blenders in additive packages, where the
concentration ranges from 1 to 20 wt-%. These additive packages are then
blended into finished oils where the typical concentration of zinc
dialkyldithiophosphate ranges from 0.1 to 10 wt-% in the finished oil.

Additive packages are shipped to customers in ships, iso-containers,
railroad tank cars, tank trucks or in 55-gallon steel drums. The
additive packages are stored in bulk storage tanks at the customer
blending sites. Finished oils are blended by pumping the lubricating oil
blend stocks and the additive package from their storage tanks through
computer controlled valves that meter the precise delivery of the
components into a blending tank. After blending, the finished lubricant
products are sold in bulk and shipped in tank trucks to large industrial
users, such as manufacturing facilities and facilities that service
truck fleets and passenger motor vehicles. Finished lubricants are also
packaged into 55-gallon drums, 5-gallon pails and one-gallon and
one-quart containers for sale to smaller industrial users. Sales of
finished lubricants in one-gallon and one-quart containers to consumers
at service stations or retail specialty stores also occur.

Based on these uses, the potentially exposed populations include (1)
workers involved in the manufacture of zinc dialkyldithiophosphates,
blending them into additive packages, and blending the additive packages
into finished lubricants; (2) quality assurance workers who sample and
analyze these products to ensure that they meet specifications; (3)
workers involved in the transfer and transport of zinc
dialkyldithiophosphates, additive packages or finished lubricants that
contain them; (4) mechanics who may come into contact with both fresh
and used lubricants while working on engines or equipment; (5) gasoline
station attendants and consumers who may periodically add lubricating
oil to automotive crankcases; and (6) consumers who may change their own
automotive engine oil. The most likely route of exposure for these
substances is skin and eye contact. Manufacturing, quality assurance and
transportation workers will likely have access to engineering controls
and wear protective clothing to minimize exposure. Mechanics wear
protective clothing but often work without gloves or eye protection.
Gasoline station attendants and consumers often work without gloves or
other protective equipment. The most likely source of environmental
exposure is accidental spills at manufacturing sites and during
transport.

# PHYSICOCHEMICAL PROPERTIES

Experimental determination of physicochemical properties of the zinc
dialkyldithiophosphates covered in this addendum is very difficult to
acquire. This is in large part due to the analytical interference
stemming from base oil used in manufacturing that cannot be removed
without altering the structural and physicochemical character of the
zinc dialkyldithiophosphate molecules. Therefore, the physicochemical
properties of CAS# 68442-22-8 presented in Table 2 are estimates based
on computer-based molecular modeling or read-across to similar materials
(refer to attached Zinc Dialkyldithiophosphate Category document).

**3.1 Justification of read-across to the Zinc Dialkyldithiophosphate
Category**

The zinc dialkyldithiophosphate covered in this addendum is a mixed
2-ethylhexyl and isopropyl derivative (CAS# 68442-22-8) which shares
extensive homology with a number of substances addressed in the existing
Zinc Dialkyldithiophosphate Category, in particular the mixed isopropyl
and 1,3-dimethylbutyl derivative (CAS# 84605-29-8) and the mixed
isobutyl and 2-ethylhexyl derivative (CAS# 26566-95-0). The molecular
weight of CAS# 68442-22-8 is bracket by the aforementioned zinc
dialkyldithiophosphate derivatives. Based on similarity of structure,
the zinc dialkyldithiophosphate addressed in this addendum is expected
to have nearly identical physical properties (e.g., liquid at ambient
temperature, decomposition at elevated temperature, very low water
solubility, low vapor pressure and logK~o/w~) to substances addressed in
the preceding Zinc Dialkyldithiophosphate Category submission. These
properties provide material support to the justification of CAS#
68442-22-8 as an extension of the existing Zinc Dialkyldithiophosphate
Category.

**TABLE 2.**

**PHYSICOCHEMICAL PROPERTIES OF A ZINC DIALKYLDITHIOPHOSPHATE**

+-------+------+-----+-----+----------+------+-----------+-----------+
| CAS   | Ave  | To  | M   | Boiling  | V    | Water     | Log       |
| N     | rage | tal | elt | Point    | apor | S         | K~o/w~    |
| umber | M    |     | ing |          | Pres | olubility |           |
|       | olec | Car | Po  | ^o^C     | sure |           |           |
|       | ular | bon | int |          | ^    | (g/L)     |           |
|       | We   | Num |     |          | (a)^ |           |           |
|       | ight | ber | ^   |          |      |           |           |
|       | (g/  | Ra  | o^C |          | (Pa) |           |           |
|       | mol) | nge |     |          |      |           |           |
+=======+======+=====+=====+==========+======+===========+===========+
| 68442 | 6    | C   | NA  | Decom    | 1.7  | 0.0158    | 2.94      |
| -22-8 | 29.4 | 12- |     | position | x    |           |           |
|       |      | C32 |     | @        | 10   | Bridging  | Bridging  |
|       |      |     |     | 120^o^C  | ^-4^ | estimated | based     |
|       |      |     |     |          |      | from CAS# | upon      |
|       |      |     |     |          |      | 8         | similar   |
|       |      |     |     |          |      | 4605-29-8 | material  |
|       |      |     |     |          |      | ^(b)^     | ^(b)^     |
+-------+------+-----+-----+----------+------+-----------+-----------+

NA -- Not applicable for liquids at ambient temperature

\(a\) 'deoiled' zinc dialkyldithiophosphates are solid, therefore vapor
pressure is best estimated by that of the diluent base oil

\(b\) Zinc Dialkyldithiophosphate Category Final Submission April 2005

**3.2 Melting Point**

Zinc dialkyldithiophosphates in lubricant base oil are liquid at ambient
temperature.

**3.3 Boiling Point**

At elevated temperatures (\> 120ºC), zinc dialkyldithiophosphates become
unstable and degrade.

### 3.4 Vapor Pressure

Due to the technical difficulty of isolating intact zinc
dialkyldithiophosphates from the highly refined lubricating base oil,
vapor pressure has not been measured on the active ingredient. The vapor
pressure of zinc dialkyldithiophosphates is best approximated to that of
the lubricating base oil and this value has been experimentally
estimated to be 1.7 x 10^-4^ Pa[^1].

### 3.5 Water Solubility

Zinc dialkyldithiophosphates are formulated for use in oils and have
very low water solubility. Water solubility testing was conducted on the
mixed isopropyl and 1,3-dimethylbutyl derivative (CAS# 84605-29-8) in
highly refined lubricating base oil (see attached Zinc
Dialkyldithiophosphate Category). This zinc dialkyldithiophosphate
shares the highest degree of homology with the substance addressed in
this addendum. A solubility of 0.0158 g/L was determined for the highly
homologous material (CAS# 84605-29-8), and this value which will serve
as a reliable estimate of the water solubility for the substance covered
under this addendum (CAS# 68442-22-8).

### 3.6 Octanol-Water Partition Coefficients

#######  

Unpublished company data on a commercial zinc dialkyldithiophosphate
with an alkyl chain length of \< 8 carbons (CAS# unassigned) yielded an
octanol/water partition coefficient (log K~ow~) value of 2.49 (see
attached Zinc Dialkyldithiophosphate Category submission). In light of
the similarities of these chemicals, this data is used as read-across to
the substance addressed in this addendum.

4.0 ENVIRONMENTAL FATE DATA

Estimated environmental fate data for the zinc dialkyldithiophosphate
covered in this addendum are summarized in Table 3 and briefly discussed
in the following sections.

**TABLE 3:**

**ENVIRONMENTAL FATE DATA**

+-------------+-------------------+-----------------+-----------------+
| **CAS       | *                 | **Hydrolysis**  | **Pho           |
| Number**    | *Biodegradation** |                 | todegradation** |
+-------------+-------------------+-----------------+-----------------+
| 68442-22-8  | Not readily       | Not readily     | [Direct         |
|             | biodegradable.    | hydrolyzed at   | Photodegradatio |
|             | Estimate based in | room            | n]{.underline}: |
|             | bridging to CAS#  | temperature,    |                 |
|             | 84605-29-8        | but readily     | Dithiophosphate |
|             | (\~5.9% in Sturm  | hydrolyzed at   | alkyl esters    |
|             | test )            | temperatures    | are not subject |
|             |                   | above 85^o^C.   | to photolytic   |
|             |                   |                 | reactions       |
+-------------+-------------------+-----------------+-----------------+

## Biodegradability

Adequate biodegradation data exists for a very similar substance (CAS#
84605-29-8) addressed in the existing Zinc Dialkyldithiophosphate
Category. The chemical addressed in this category addendum (CAS#
68442-22-8) has highly homologous construction and therefore are
expected to be poorly biodegraded as well.

## Hydrolysis

Zinc dialkyldithiophosphates are formulated in oil and are
hydrolytically stable under recommended storage and transportation
conditions. Further, these substances (including CAS# 68442-22-8) have
little, if any, potential for hydrolysis under environmentally relevant
conditions. Studies have been conducted which demonstrate that zinc
dialkyldithiophosphates readily hydrolyze at \> 85ºC (per existing Zinc
Dialkyldithiophosphate Category document).

## 

## Photodegradation

In order to evaluate if direct photolysis is a relevant fate mechanism
for zinc dialkyldithiophosphates, the UV light absorption spectra was
taken for the mixed isopropyl and 1,3-dimethylbutyl derivative (CAS \#
84605-29-8; refer to the Zinc Dialkyldithiophosphate Category document).
The absorbance maximum for CAS \# 84605-29-8 was 1.0957 AU at 202 nm
which indicates that direct photolysis is not a relevant pathway for
members of this category. No photodegradation studies were therefore
conducted on the substance addressed in this addendum. Indirect
photodegradation as a result of hydroxyl radical interaction is not a
significant pathway as this substance is not volatile and will not exist
in a vapor phase.

## Fugacity

##### 

Fugacity-based multimedia fate modeling compares the relative
distribution of chemicals among environmental compartments. The EQC
Level I model was utilized to evaluate the distribution of the zinc
dialkyldithiophosphate in the environment. As summarized in table 4,
fugacity modeling was conducted on representative zinc
dialkyldithiophosphate which covers both the low and high molecular
weight members. The results show that the zinc dialkyldithiophosphates
will partition preferentially into the soil and sediment compartment.
This is consistent with the physical-chemical properties (low water
solubility, elevated log K~o/w~ and low vapor pressure) and the fact
that these substances are manufactured and processed in petroleum base
oils.

**TABLE 4**

**ENVIRONMENTAL DISTRIBUTION DATA**

**Modeled by EQC Level I^1^**

^1^Read-across to the homologous zinc dialkyldithiophosphate identified
in the existing Zinc Dialkyldithiophosphate Category dossier by the CAS#
84605-29-8

#  Aquatic Toxicity Data

Acute fish, invertebrate and alga toxicity testing was not conducted on
CAS# 68442-22-8. Rather, data extrapolated from a highly homologous zinc
dialkyldithiophosphate (CAS# 84605-29-8) was used as read-across (Table
5).

> **TABLE 5**
>
> **AQUATIC TOXICITY DATA**

+-----------+-----------------+------------------+--------------------+
| CAS       |                 |                  |                    |
|           |                 |                  |                    |
| Number    |                 |                  |                    |
+===========+=================+==================+====================+
|           | Fish            | Invertebrates    | Algae              |
+-----------+-----------------+------------------+--------------------+
| 6         | LL~50~ = 4.5    | EL~50~ = 10 -    | E~b~L~50~ = 10 -   |
| 8442-22-8 | mg/L            | 100 mg/L         | 100 mg/L           |
|           |                 |                  |                    |
|           | Estimated by    | Estimated by     | Estimated by       |
|           | bridging to     | bridging to CAS# | bridging to        |
|           | CAS# 84605-29-8 | 84605-29-8       |                    |
|           |                 |                  | CAS# 84605-29-8    |
+-----------+-----------------+------------------+--------------------+

Acute aquatic toxicity studies were conducted on CAS# 84605-29-8 using
water accommodated fraction (WAF) which consists of a water-soluble
extract of test material, but it can also include a stable
micro-emulsion or contain small amounts of suspended matter. CAS \#
84605-29-8 was found to exhibit moderate toxicity to fish with 96-hour
median lethal concentration (LC~50~) of 4.5 mg/L. It was relatively less
toxic to invertebrates and algae with median effects concentration
(EC~50~) in 10 -- 100 mg/L range. In light of the high degree of
chemical similarity between the tested substance and the substance
addressed in this addendum, this data is deemed reliable for
characterization of the acute aquatic toxicity of CAS# 68442-22-8.

#  Mammalian Toxicity Data

## 

## Acute Mammalian Toxicity 

Estimates of acute toxicity of the zinc dialkyldithiophosphate covered
in this addendum when administered by the oral or dermal route is
summarized in Table 6. By virtue of the high degree of homology between
the zinc dialkyldithiophosphate covered in this addendum (mixed
isopropyl and 2-ethylhexyl; CAS#68442-22-8) and a zinc
dialkyldithiophosphate for which experimental data exists (mixed
isopropyl and 1,3-dimethylbutyl; CAS# 84605-29-8; refer to Zinc
Dialkyldithiophosphate Category document) a read-across argument
supports that the zinc dialkyldithiophosphate covered in this addendum
has a low order of acute toxicity.

**TABLE 6**

**ACUTE TOXICITY DATA**

+-----------+-----------------------------+---------------------------+
| CAS       | ACUTE ORAL TOXICITY         | ACUTE DERMAL TOXICITY     |
| Number    |                             |                           |
+===========+=============================+===========================+
| 6         | LD~50~ \> 2.0 g/kg (rat)    | LD~50~ \> 20.0 g/kg       |
| 8442-22-8 |                             | (rabbit)                  |
|           | Estimated by bridging to    |                           |
|           | CAS# 84605-29-8             | Estimated by bridging to  |
|           |                             | CAS# 84605-29-8           |
|           |                             |                           |
|           |                             | []{.mark}                 |
+-----------+-----------------------------+---------------------------+

## Repeated Dose Toxicity

An estimation of the repeated-dose systemic and
reproduction/developmental toxicity of the zinc dialkyldithiophosphate
covered in this addendum is presented in Table 7.

**TABLE 7**

**REPEATED-DOSE TOXICITY DATA**

+---------+----------------------------------+------------------------+
| **CAS   | **REPEATED-DOSE SYSTEMIC         | REPRODUCTIVE/          |
| N       | TOXICITY**                       |                        |
| umber** |                                  | **DEVELOPMENTAL        |
|         |                                  | TOXICITY**             |
+=========+==================================+========================+
| 684     | 21-day repeated-dose dermal      |                        |
| 42-22-8 | study in rabbits                 |                        |
|         |                                  |                        |
|         | NOAEL not established (adverse   |                        |
|         | effects at all doses) -- based   |                        |
|         | on read-across to CAS#           |                        |
|         | 26566-95-0                       |                        |
+---------+----------------------------------+------------------------+
|         | 28-day repeated-dose oral study  | Repr                   |
|         | in rats (OECD 407) NOAEL = 10    | oduction/developmental |
|         | mg/kg/day -- based on            | oral toxicity          |
|         | read-across to CAS# 4259-15-8    | screening test in rats |
|         |                                  | (OECD 421)             |
|         |                                  |                        |
|         |                                  | NOAEL P0 = 30          |
|         |                                  | mg/kg/day              |
|         |                                  |                        |
|         |                                  | NOAEL F1 = 30          |
|         |                                  | mg/kg/day              |
|         |                                  |                        |
|         |                                  | Based on read-across   |
|         |                                  | to 4259-15-8           |
+---------+----------------------------------+------------------------+

### Systemic Toxicity

Commercial samples of the mixed isobutyl and 2-ethylhexyl derivative
(CAS \# 26566-95-0), and the 2-ethylhexyl derivative (CAS \# 4295-15-8)
were each evaluated in separate repeated-dose toxicity studies by both
the oral and dermal routes of administration (refer to the attached Zinc
Dialkyldithiophosphate Category Document). These substances serve as
adequate read-across to the chemical addressed in this addendum in that
all substances share common C~3~ - C~8~ alkyl side chains around a
phosphorodithioic acid core. In the repeated dose dermal studies
exposure of these substances to rabbits can cause moderate-to-severe
dermatitis, significant loss of body weight, behavioral distress,
reductions in hematology parameters, loss of normal testicular function,
and even death at the higher doses. In fact, these effects were observed
across several members of the category with carbon chain lengths ranging
from C~3~-C~8~ (refer to Appendix). Repeated oral administration of CAS#
4295-15-8 resulted in evidence of severe gastrointestinal irritation
with submucosal edema and suppurative inflammation, mucoid diarrhea,
significant body weight loss, distress, and death at the higher doses.
However, no significant adverse effects were noted on the testes or male
accessory reproductive organs. There was no evidence that the
incremental changes in carbon chain length or molecular weight could be
correlated with significant changes in dermal or oral toxicity
parameters.

### Reproductive and Developmental Toxicity

Reproduction/developmental toxicity data is available for a commercial
sample of the 2-ethylhexyl derivative (CAS# 4295-15-8; refer to Zinc
Dialkyldithiophosphate Category document). Although the repeated dose
dermal toxicity studies indicated that exposure to zinc
dialkyldithiophosphates can have adverse effects on testicular function,
it is believed that these effects are secondary to profound dermal
irritation, body weight loss and stress. This is evidenced by the lack
of reproductive organ effects in the oral reproduction/developmental
toxicity assay observed with the 2-ethylhexyl derivative and supportive
literature linking dermal irritation and testicular function in
experimental animals. Furthermore, epidemiological studies support the
lack reproductive findings in experimental analyses. In 1980, National
Institute for Occupational Safety and Health investigators conducted a
survey to obtain process and toxicology research information, and to
conduct employee interviews at a zinc dialkyldithiophosphate production
plant[^2]. The plant produced zinc dialkyldithiophosphates of various
chain lengths ranging from C~3~-C~8~. Review of medical histories showed
no significant difference between the "exposed" and "controls" zinc
dialkyldithiophosphate manufacturing plant workers with regard to birth
defects in offspring, infertility, or miscarriages and stillbirths
experienced by wives or partners. Physical examination showed no gross
abnormalities in secondary sexual characteristics for exposed and
controls. Semen analysis showed no azoospermia or oligospermia in the
exposed group. Other parameters of the semen analysis showed no
significant difference between exposed and controls. The conclusion of
the report was that workers exposed to zinc dialkyldithiophosphates in
an occupational setting did not exhibit untoward effects on reproductive
health when compared to workers not exposed to such compounds. The
totality of the repeated dose toxicity data indicates that the
reproductive organ effects observed in male rabbits are attributed to
the stress associated with the severe dermal responses to the test
material, rather than direct a systemic response to the test materials.
Changes in male reproductive organs in the rabbit have been observed
when other irritating substances are applied to the skin at dose levels
that cause skin lesions.[^3]^,^[^4] Thus, dermal irritation alone, or in
combination with the accompanying weight loss and stress, is thought to
play a role in the reproductive organ response to repeated cutaneous
application of zinc dialkyldithiophosphates.

## 7.0 GENOTOXICITY

The genotoxicity potential of CAS# 68442-22-8 is estimated by
read-across to similar materials, and this data is presented in Table 8.
*In vitro* bacterial gene mutation assays, *in vitro* mammalian gene
mutation assays, or *in vivo* chromosomal aberration assays have been
conducted for many of the zinc dialkyldithiophosphates in the existing
Category dossier (see Appendix). Based upon structural similarities to
the mixed isopropyl and 1,3 dimethylbutyl derivative (CAS# 84605-29-8)
and the mixed isobutyl and 2-ethylhexyl derivative (CAS# 26566-95-0),
the genotoxicity data from these substances serves as adequate
read-across to the mixed isopropyl and 2-ethylhexyl derivative (CAS#
68442-22-8) addressed in this addendum. The findings from the bacterial
reverse mutation assay and *in vivo* mouse micronucleus tests were
negative for mutagenic potential for all of the tested materials with
alkyl side chains that ranged from mixed C~3~ to C~8~. The results from
the *in vitro* mammalian cell gene mutation test gave inconsistent
results for four members of the category with alkyl side chains that
ranged from mixed C~4~-C~8~. The results from the *in vitro* BALB/3T3
point mutation (ouabain locus) and cell transformation assays indicate
that zinc dialkyldithiophosphates may have genotoxic potential. However,
dermal carcinogenicity tests conducted in mice revealed that new motor
oils containing between 1% and 3% zinc dialkyldithiophosphate were found
to be non-carcinogenic (American Petroleum Institute). The weight of
evidence supports the conclusion that zinc dialkyldithiophosphates,
including CAS# 68442-22-8, have a low potential genotoxicity, and that
these substances do not present a significant risk for mutagenicity or
carcinogenicity in humans.

**Table 8.**

**Genotoxicity Data**

+-----------+-------------------------------------+--------------------+
| CAS       | GENE MUTATION ASSAY                 | CHROMOSOMAL        |
| Number    |                                     | ABERRATION ASSAY   |
+===========+=====================================+====================+
| 6         | Mutagenic under certain             | Not clastogenic    |
| 8442-22-8 | experimental conditions.            |                    |
|           |                                     | Based upon         |
|           | Based upon bridging to data on CAS# | bridging to data   |
|           | 84605-29-8 and 26566-95-0           | on CAS# 84605-29-8 |
|           |                                     | and 26566-95-0     |
+-----------+-------------------------------------+--------------------+

####### 

[^1]: HPV Chemical Challenge Program - Test Plan for Lubricating Oil
    Basestocks Category submitted to the US EPA by the Petroleum HPV
    Testing Group. March 24, 2003.

[^2]: NIOSH Health Hazard Evaluation Report HETA 80-228-1241, 1980.

[^3]: Wong, Z. A., VonBurg, R., Spangler, W. L., and MacGregor, J. A.
    (1982) Testicular Damage in the Rabbit Resulting from Simple
    Chemical Cutaneous Irritation. The Toxicologist [2]{.underline}: 41.

[^4]: McKee, R. H., Kapp, Jr., R. W., and Ward, D. P. (1985) Evaluation
    of the Systemic Toxicity of Coal Liquefaction-Derived Materials
    Following Repeated Dermal Exposure in the Rabbit. J. App. Toxicol.
    [5]{.underline}: 345-351.