Dimethyl octadecylphosphonate

PBT assessment

PBT assessment: overall result

PBT status:

the substance is not PBT / vPvB

Justification:

PBT/vPvB criteria and justification

Assessment of PBT/vPvB Properties - Comparison with the Criteria of Annex XIII

PBT and vPvB criteria according to Annex XIII of the REACH Regulation

Property	PBT-criteria	vPvB-criteria
Persistence	-   T½ > 60 days in marine water, or -   T½ > 40 days in fresh- or estuarine water, or -   T½ > 180 days in marine sediment, or -   T½ > 120 days in fresh- or estuarine sediment, or -   T½ > 120 days in soil.	-   T½ > 60 days in marine, fresh- or estuarine water, or -   T½ > 180 days in marine, fresh- or estuarine sediment, or -   T½> 180 days in soil.
Bioaccumulation	-   BCF > 2000 L/kg	-   BCF > 5000 L/kg
Toxicity	-   NOEC < 0.01 mg/L for marine or freshwater organisms, or -   substance is classified as carcinogenic (category 1 or 2), mutagenic (category 1 or 2), or toxic for reproduction (category 1, 2 or 3), or -   there is other evidence of chronic toxicity, as identified by the classifications: T, R48, or Xn, R48 according to Directive 67/548/EEC.	-

Persistence Assessment

Testing to assess the biodegradation of dimethyl octadecylphosphonate (DMOP) is not feasible since DMOP is highly insoluble in water (the water solubility was visually assessed to be <1.07E-03 g/l at 20.0 ± 5°C (Fox, 2013) which is supported by the value of 7.656E-07 g/l at 25°C derived from the (Q)SAR WSKOW (v1.42)). 

The (Q)SAR BIOWIN (v4.10) indicates that DMOP is not readily biodegradable (Non-linear model prediction (BIOWIN 2), however according to BIOWIN 3 and BIOWIN 4, DMOP is subject to ultimate biodegradation over a period of weeks/months and primary degradation over days/weeks, respectively. The output from EPI Suite v4.1.1 which includes the data from BIOWIN (v4.10) for DMOP is presented in full in Appendix 3 and a summary of the data is presented below:

Model		Value	Result
BIOWIN 2	Non-Linear Model Prediction	0.4266	does not biodegrade fast
BIOWIN 6	MITI Non-Linear Model Prediction	0.3588	does not biodegrade fast
BIOWIN 3	Ultimate Biodegradation Timeframe	2.6963	ultimate biodegradation: Weeks-Months
BIOWIN 4	Primary Biodegradation Timeframe	3.5938	Primary Biodegradation: days/weeks

The criteria defined for persistence in Chapter R11 – PBT Assessment are

•             Non-linear model prediction (BIOWIN 2): does not biodegrade fast (probability < 0.5) and ultimate biodegradation timeframe prediction (BIOWIN 3): ≥ months (value < 2.2),or

•             MITI non-linear model prediction (BIOWIN 6): does not biodegrade fast (probability < 0.5) and ultimate biodegradation timeframe prediction (BIOWIN 3): ≥ months (value < 2.2)

DMOP does not meet the criteria above for persistence since the value from BIOWIN 3 is > 2.2 (a value of 2.6963 was derived for DMOP from BIOWIN 3).

The level III Fugacity Model (EPI-Suite V4.1.1) predicts that the DT₅₀for DMOP in soil) is 75 days which is considerably less than 120 days which is defined in the Annex XIII of the REACH Regulation.Soil is the most relevant environmental compartment since DMOP has a Log Koc of > 5.73 (Koc > 427,000) and therefore DMOP will partition into soil if released to the environment.

It can therefore be concluded that DMOP does not meet the criteria for persistence.

In addition, data obtained using the US EPA PBT profiler demonstrates that substances with structures analogous to DMOP do not meet the criteria for persistence. Phosphonic acid, methyl-, dimethyl ester (CAS No. 756-79-6) has an estimated DT₅₀in soil and water of 30 days and 15 days, respectively. Phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-,diethyl ester, CAS No. 2781-11-5 has an estimated DT₅₀in soil and water of 75 and 38 days, respectively. The U.S. EPA assessment of Phosphonic acid, P-[[bis(2-hydroxyethyl) amino]methyl]-,diethyl ester also concludes that the substance has a low potential for persistence (Screening Level Hazard Assessment for Fyrol 6, CASRN 2781-11-5, U.S. EPA, September, 2009). 

Bioaccumulation Assessment

Experimental data for derivation of aquatic bioconcentration are not available. Testing has not been conducted since exposure to the aquatic environment is expected to be limited. According to the ATIEL Group SpERCs factsheets for formulation of lubricant additives, lubricants and greases (for example, SPERC Factsheet Ai-add-pack-(2012-10-05)) “User sites are assumed to be provided with oil/water separators or equivalent and for waste water to be discharged via public sewer system”. In addition, the exposure and risk assessment for formulation (note:- formulation is considered to represent a worst case scenario relative to professional and consumer use) based on EU tonnage and calculated using the OECD ESD No. 10 on Lubricants and Lubricant Additives combined with EUSES v2.1.2, indicates that there is no cause for concern for the environment. The Risk Characterisation Ratios for the aquatic environment were all <1.

The estimated BCF derived from BCFBAF v3.01 is 686.4 L/kg and the estimated BCF value derived from the Arnot-Gobas method is <141.5 l/kg. BCFBAF v3.01 meets the OECD principles of (Q)SAR and the experimental Log Kow of 8.41 is within the limits of the model.

Since these estimated BCF values are < 2000 L/kg, DMOP does not meet the criteria for bioaccumulation.

In addition, data obtained using the US EPA PBT profiler demonstrates that substances with structures analogous to DMOP do not meet the criteria for bioaccumulation. Phosphonic acid, methyl-, dimethyl ester (CAS No. 756-79-6) has an estimated BCF value of 3.2. Phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-,diethyl ester, CAS No. 2781-11-5 also has an estimated BCF value of 3.2. The U.S. EPA assessment of Phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-,diethyl ester also concludes that the substance has a low potential for bioaccumulation (Screening Level Hazard Assessment for Fyrol 6, CASRN 2781-11-5, US EPA, September, 2009). 

Toxicity Assessment

Human Health Assessment

Carcinogenicity

This endpoint is not required based on tonnage.

Mutagenicity

Study data from onein-vitrostudy in bacterial cells and twoin-vitrostudies in mammalian cells were performed and are summarised in the following table:

Study	Method	Result
in vitro mutagenicity in bacteria Riach, C G (2012) Dimethyl Octadecylphosphonate: Bacterial Reverse Mutation Test in Salmonella typhimurium TA 1535, TA 100, TA 1537 and TA 98 and Escherichia coli WP2uvrA (OECD 471). Charles River Report No. 33550.	OECD Guideline 471 (Bacterial Reverse Mutation Assay)	DMOP was not mutagenic in strains ofSalmonella typhimuriumandEscherichia coliwhen dissolved and diluted in ethanol and tested in the absence and presence of metabolic activation at concentrations up to and above its limit of solubility in the test system.
in vitro cytogenicity study in mammalian cells Riach, C G (2012) Dimethyl Octadecylphosphonate: In vitro Mammalian Cell Gene Mutation Tes in Mouse Lymphoma L5178Y Cells (OECD 476). Charles River Report No. 33901.	OECD Guideline 476 (Test in Mouse Lymphoma L5178Y Cells)	DMOP was not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of metabolic activation when tested in ethanol at concentrations extending into the toxic range.
in vitro gene mutation in mammalian cells Murie, E (2013) Dimethyl Octadecylphosphonate: In vitro Mammalian Chromosome Aberration Test in Chinese Hamster Ovary Cell Cultures. Charles River Report No. 33743.	OECD Guideline 473 (In VitroMammalian Chromosome Aberration Test)	DMOP was not clastogenic when tested with Chinese hamster ovary cell in vitro.

It can be concluded that DMOP should not be classified as mutagenic.

Toxicity to Reproduction

In a 28-day repeated dose toxicity and reproduction/developmental toxicity screening test performed using rats according to OECD 422, the data did not identify an effect on fertility, reproductive performance or development and viability of the offspring over days 1 to 5 of lactation, at dose levels up to and including 600 mg/kg bw/day. DMOP should not, therefore, be classified for reproduction toxicity.

Chronic Toxicity

Chronic toxicity testing was not performed since the data are not required based on the tonnage of DMOP (i.e. 100 – 1000 tonnes). In consideration of the data from the rat 28-day repeated dose toxicity and reproduction/developmental toxicity screening test (Note:- DMOP was administered for up to 60 days in this study and was performed according to OECD Guideline 422) sub-chronic toxicity testing was not merited. It is considered that a 90-day study is not scientifically justified on the basis that sufficient information is available to characterise the repeat-dose toxicity of DMOP. The data are summarised in the following table:-

Study	Discussion	Data
Chronic Toxicity (>12 months)	Chronic toxicity testing is not required based on tonnage.	Not applicable
Sub-chronic toxicity (90-day study)	Tests were not performed since further testing was not merited given the data from the rat 28-day repeated dose toxicity (DMOP was administered for up to 60 days in this study).	Not applicable
28 repeated dose toxicity Zmarowski, A (2013) Combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of M-5925 in rats by oral gavage. Will Research Europe B.V. Project No. 500036.	A 28-day repeated dose toxicity and reproduction/developmental toxicity screening test In rats was performed (OECD Guideline 422).	Parental NOAEL: 300 mg/kg/day (males/females) (Males were exposed for 36 days. Females were exposed for 47-60 days)

The duration of treatment in the OECD 422 repeated-dose study ranged from 36 days (males) to up to 60 days (females). Based on the longer duration of treatment and in consideration of the findings at 1000/600 mg/kg bw/day not being representative of significant toxicity, it is not considered that the NOAEL of 300 mg/kg bw/day merits classification with regard to specific target organ toxicity – repeated exposure (STOT-RE). DMOP should not, therefore, be classified with respect to repeat dose toxicity.

Environmental Assessment

A 48-hour static acute toxicity study with Daphnia magna was performed in a test designed to meet the requirements of OECD Test Guideline 202. As DMOP is highly insoluble in water the water-accommodated fraction (WAF) procedure was applied to prepare the test solutions. In the limit test where 20 daphnids were exposed to a nominal loading rate of 100 mg/l for 48 hours and a second group of 20 daphnids was exposed to dilution test water (control solution), no immobilisation was observed in any of the test solutions at 0, 24 or 48 hours. The EL50 (Median Effective Loading rate) was >100 mg/l and the No Observed Effect Loading rate was ≥100mg/l.

Species	Endpoint	Reference
Invertebrate toxicity	48-hour EL50 (Median Effective Loading rate) inDaphnia magna(EL50 = >100 mg/L)	L'Haridon, J. (2006). Toxicity in Daphnia Magna Under Static Conditions: CIT Report No. 31708 EAD.

Based upon the above mentioned short-term aquatic toxicity study DMOP should not be classified as Toxic.

Overall, DMOP should not, based upon a review of the human health and environmental data, be considered to be toxic.

In conclusion, DMOP is not Persistent (P), Bioaccumulative (B) or Toxic (T).

Likely routes of exposure:

Aquatic Environment

Exposure of DMOP to the aquatic environment is expected to be limited, according to ATIEL Group Specific Environmental Release Categories (SpERCs) factsheet for formulation of lubricant additives, lubricants and greases (SPERC Factsheet Ai-add-pack-(2012 -10 -05)) “User sites are assumed to be provided with oil/water separators or equivalent and for waste water to be discharged via public sewer system”. In addition, the exposure and risk assessment for formulation (note:- formulation is considered to represent a worst case scenario relative to professional and consumer use) of DMOP, based on EU tonnage, and calculated using OECD ESD No.10 for Lubricants and Lubricant Additives combined with EUSES v2.1.2, indicates that there is no cause for concern for the aquatic environment.

Terrestrial Environment

No direct exposure of DMOP to soil is expected for industrial uses, as supported by the ATIEL-ATC SpERCs where it is stated, " Surveys (ATIE-ATC questionnaire responses 2010) have revealed that no biosolids of industrial origin are applied to land (in line with national regulations) and are incinerated". For professional and consumer uses the SpERCs indicated very limited emissions. ATIEL-ATC SPERC Factsheet Bp (2012-10-05) and SPERC Factsheet Cp (2013-02-07) states, "1E-03 Default assumptions taken from EUTGD, 2003: Table A3.8 3", and SPERC Factsheet Bc (2012-10-05) and SPERC Factsheet Cc (2013-02-07) states "1E-04 Default assumptions taken from EUTGD, 2003: Table A4.2 ". In addition, the exposure and risk assessment calculated using the EU tonnage and the OECD ESD No. 10 for Lubricants and Lubricant Additives combined with EUSES v2.1.2, indicates that there is no cause for concern with regard to the environment. The Risk Characterisation Ratios, calculated using the soil PNEC derived using equilibrium partitioning method, were all <1.