1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Endpoint summary

Description of key information

 

AIR COMPARTMENT

DIRECT PHOTOLYSIS

Octopirox does absorb light >290 nm (ozone band) and therefore a direct photolysis in air may occur. Measurements on Direct Photolysis are not available but in water (see IUCLID Section 5.1.3). It can be expected that the Direct Photolysis in air is even faster than in water.

INDIRECT PHOTOLYSIS

OH radical induced indirect photolysis of Octopirox can be calculated with US EPA AOPWIN Program estimating low degradation half-lives of 5h (neutral form of Octopirox). Half-life for the reaction with ozone is 48 min. As Octopriox has a low vapour pressure, is water soluble (see IUCLID Section 4.8) and has therefore a low Henry’s Law Constant of 1.1*10-7 Pa*m3/mole (see IUCLID Sections 4.6 & 4.8), volatilisation is not an exposure route which has to be considered.

 

WATER COMPARTMENT

HYDROLYSIS

Octopirox has no functional groups which could be hydrolyzed under environmental conditions at pH 4-9 (see OECD Guideline 111). But in the dark reaction carried out in the Direct photolysis experiment (see IUCLID Section 5.1.3) Octopriox disapperared at pH 9 with a Half-life of 2.7 d and at pH4 with 12d. This could be interpreted as hydrolysis e.g. ring opening of the heterocycle but the transformation products could not be identified. The half-life of the Direct photolysis (at pH 4 0.2h at 24 deg C, pH 9 0.6h at 27 deg C) is much lower as for hydrolysis in the dark reaction described before.

DIRECT PHOTOLYSIS

Coiffard et al (Pharma Science, 1996, 6, 455 -458) had investigated the direct photolysis of Octopirox at pH7 with spectrometry as analytical method and found rapid transformation. Clariant was interested to carry out the direct photolysis at pH 4 (neutral form of Octopirox) and pH 9 (ionic form of Octopriox) to investigate possible differences. In addition a substance specific analysis with HPLC and LC MS MS was applied to identify also possible metabolites.

Octopirox degrades rapidly by Direct photolysis (OECD 316). The half-life at pH 4, 24 deg C is 0.2 h and at pH 9, 27 deg C 0.6h.

During direct photolysis in water the first metabolite formed is the ring-N deoxygenated Octopirox (NDO). NDO is formed at 0.032 1/h at pH 9 and 1.2 1/h at pH 4. NDO itself is further transformed with a half-life of 16h. After 125h (ca. 5d) of direct photolysis Octopirox was completely disintegrated means no pyridinone chromophore could be detected any more.At pH4 a DOC removal of 31% could be observed during the full period of the photolysis. During direct photolysis other non aromatic metabolites were formed but the structure of these metabolites could not be evaluated. Some hints of possible structures are published in the open literature (Taylor et al, JACS 1961, 83, 4484 -85, Redmond et al. JACS 1996, 118, 10124 -10133).

 

INDIRECT PHOTOLYSIS

In principle indirect photolysis of Octopirox should also occur not only in air but also in water as OH radicals may be formed from sensitizers like humic acid and sunlight. But it is likely that indirect photolysis in water is slower than direct photolysis.

 

SOIL COMPARTMENT

DIRECT PHOTOLYSIS ON SOIL SURFACES

As reported in IUCLID SECTION 5.1.3 Octopriox is rapidly degraded by DIRECT Photolysis in water at pH 4 and 9. Direct Photolysis on soil surfaces are carried out similarly to the Direct photolysis in water (see proposed OECD Guideline on 'Phototransformation of Chemicals on Soil surfaces). So it is very likely that Octopirox is also rapidly degraded when photolyzed on soil surfaces.

BIODEGRADATION IN WATER: SCREENING TESTS

AEROBIC TESTS - Table 1

Guideline	Test substance	Duration	Endpoint	Biodegradation	Result
OECD 301B	Octopriox	28d	CO2 Evolution	6 %	not readily biodegradable under the test conditions
OECD 301B	2 -Pyridinol-N-oxid	28d	CO2 Evolution	77%	readily biodegradable
OECD 301B	Octopirox Fe(III)	28d	CO2 Evolution	6 %	not readily biodegradable under the test conditions
OECD 301D	Octopirox	28d	O2 Consumption	14%	not readily biodegradable under the test conditions
OECD 302B	Octopirox	28d	DOC removal	n.a.	sorption and biodegradation cannot be distinguished

ANAEROBIC TEST - Table 2

Guideline	Test substance	Duration	Endpoint	Biodegradation	Result
OECD 311	Octopirox	58d	Biogas Evolution	0 -10 %	not biodegradable under the anaerobic test conditions

BIODEGRADATION IN WATER: SIMULATION TEST IN SEWAGE TREATMENT PLANT

In the followingTable 3a Mass balance is given for the Simulation test system based on daily sampling over 24d

	Effluent	Sludge	Total	Sorption to Glass& Tubing (estimated)	Remark
95% CI	3.5 - 4.1 %	85 - 95 %	87 - 99 %	n.a.	analytical recovery forOctopirox was excellent
arithm. mean	3.8 %	90 %	93 %	< 5%	Biodegradation is minor

For the Sewage treatment modelling the mass balance was set to 4% release to effluent and 96% to sewage sludge.

BIODEGRADATION IN SEDIMENT

No data are available. Based on the aquatic Biodegradation data listed above rapid biotic degradation is not expected. As Octopirox is rapidly degraded by Direct photolysis in water this is the rate determining step for the fate and not biodegradation. Therefore a Sediment Simulation Test is not warranted.

BIODEGRATION IN SOIL

No data are available. Based on the aquatic Biodegradation data listed above rapid biotic degradation is not expected. As Octopirox is rapidly degraded by Direct photolysis in water this is the rate determining step for the fate in the aquatic compartment and not biodegradation. As Direct Photolysis on soil surfaces may also occur a Soil Simulation test is not warranted.

SUMMARY ON BIODEGRADATION

AQUATIC BIODEGRADATION

Whereas 2 -Pyridinol-N-oxid which is the unsubstitueted moeity of Octopirox is readily biodegradable Octopirox is not. The reason is most likely the branched alkyl side chain. This means the rate for ultimate biodegradation of Octopirox compared to 2 -Pyridinol-N-oxide is much lower due to the slow degradation of the alkyl side chain. But Octopirox is not recalcitrant especially due to the rapid Direct photolysis in water (see IUCLID Section 5.1.3).

SEDIMENT & SOIL BIODEGRADATION

Based on the data from the biodegradation tests in water rapid biodegradation is not expected in sediment and soil. As Direct photolysis in water is rapid this is the rate determining step in the fate of Octopirox in water a Sediment Simulation test is not warranted. Direct photolysis can also occur on soil surfaces and therefore a Soil Simulation test is not warranted.

BIOACCUMULATION IN WATER/SEDIMENT

Octopirox is a weak acid with a pKa of 5.9. This means the neutral form of Octopriox is deprotonated at high pH and is ionic. At pH4 most of the Octopirox exists in the neutral form whereas at pH 9 almost all Octopirox exists in the ionic form. Clariant has measured the n-Octanol solubility of Octopriox which is 37.5 g/L. The water solubility of Octopriox is pH dependant: pH4 22.1 mg/L, pH7 29.8 mg/L and pH9 473 mg/L. This results in a Log Coctanol/Cwater of 3.2 for pH4, 3.1 for pH7 and 1.9 for pH9. As expected the ionic form of Octopirox at pH 9 has the lowest partitioning coefficient. In order to confirm these estimates an OECD 107 Shake flask test was carried and the Log Kow was measured to be 3.86 at pH4 (neutral form: worst case). Based on the CLP Criteria for Bioaccumulation e.g. Log Kow >=4 or REACH PBT & vPvB B Screening criteria of Log Kow >4.5 these criteria for Octopirox are not fullfilled. The BCF and BAF for the neutral form of Octopirox can be estimated with the program US EPIWIN 4.2: BCF=131 L/kg and BAF=230 L/kg wet weight. These estimates support a low bioaccumulation potential of Octopirox. Therefore a Bioaccumulation study in water/sediment is not warranted. The statement given above fulfills the requirement for waiving as given in 1907/2006/EC Annex IX, Column 2, 9.3.2: The study need not be conducted if the substance has a low potential for bioaccumulation and /or a low potential to cross biological membranes.

BIOACCUMULATION IN SOIL

Octopirox is a weak acid with a pKa of 5.9. This means the neutral form of Octopriox is deprotonated at high pH forming an ionic form. At pH4 most of the Octopirox exists in the neutral form whereas at pH 9 almost all Octopirox exists in the ionic form. Clariant has measured the n-Octanol solubility of Octopriox which is 37.5 g/L. The water solubility of Octopriox is pH dependant: pH4 22.1 mg/L, pH7 29.8 mg/L and pH9 473 mg/L. This results in a Log Coctanol/Cwater of 3.2 for pH4, 3.1 for pH7 and 1.9 for pH9. As expected the ionic form of Octopirox at pH 9 has the lowest partitioning coefficient. In order to confirm these estimates an OECD 107 Shake flask test was carried and the Log Kow was measured to be 3.86 at pH4 (neutral form: worst case). No Bioaccumulation criteria for the soil compartment exist. But it is very likely that Octopirox has also in the terrestrial compartment a low bioaccumulation potential as in the aquatic compratment (see IUCLID Section 5.3.1). This is confirmed by the QSAR estimate for BCF worm of the neutral form of Octopirox calculated by EUSES Version 2.1 which is 96 L/kg ww.

ADSORPTIION DESORPTION BEHAVIOUR

[14C]-Octopriox Adsorption Desorption test according OECD 106

As Octopirox exists in an ionic form at higher pH it can sorb not via van der Waal forces but also by ionic interactions (e.g ion pair formation, cation exchange). So far no mechanistic model exists to estimate the sorption behaviour of these substances. Therefore measurements are warranted to address the sorption to solid phases reliably. Sorption was measured in three different soils, one sediment and one secondary sludge. The Freundlich isotherms for the different matrices are non-linear (1/n < 1). As the lowest tested concentration is used for the exposure assessment, Table 5.4-1 below lists the Kd and Koc at that concentration which allows to judge the sorption behaviour without a calculation excerise using the Freundlich isotherm.

  

Table 5.4       Sorption behaviour of [14C]-Octopirox to different solid matrices

 

SOIL		% OC		% Clay		CEC (Meq/100g)	Kd (L/kg) lowest conc.Measured		Koc (L/kg) lowest conc.Measured
Cranfield 164		3.7		28		22.8	4885		132027
Cranfield 277		2.7		57		22.4	4800		177778
Cranfield 299		2.9		26		14.9	4172		143862
mean		3.1		34		15.3	4619		149000
SEDIMENT
SW		6.2		25		21.7	3782		61000
SLUDGE
secondary (activated)		37.5		59		96	1477		3939

 

 The Koc values from the OECD 106 study were used in the Environmental exposure assessment of Octopirox carried out with the EUSES model. As EUSES assigns certain percentages of organic carbon (OC) to the different compartments, Kd values for EUSES were calculate from the available Koc as given in the table 5.4-2

  

Table 5.4-2    Recalculation of Sorption constants for Octopirox to values which can be used in the EUSES Exposure assessment

 

	OECD106 results at 10 µg/L Octopirox		EUSES STANDARD VALUES %OC and Kd related to Koc
SOIL
	% OC	Koc (L/kg) average lowest conc.Measured	% OC EUSES	Kd (L/kg) EUSES based on EUSES OC	EUSES Term for Compartment
Cranfield 164	3.7	132027
Cranfield 277	2.7	177778
Cranfield 299	2.9	143862
mean	3.1	149000 (based on mean values Kd & OC %)	2	2980	SOIL
SEDIMENT
SW	6.2	61000	5	3050	SEDIMENT
SLUDGE
secondary (activated)	37.5	3939	37	1457	ACTIV. SLUDGE

 

Octopirox considerably sorbs to solid matrices especially to soils and sediment.  

Henry’s Law Constant (HLC)

The HLC of the neutral form of Octopirox can be calculated from vapour pressure (IUCLID Section 4.6) water solubility (IUCLID Section 4.8). The Exposure assessment tool EUSES 2.1 recalculates the HLC of 1*E-3 Pa*m3*mol-1at 25 degree C to 4.8*E-4 Pa*m3*mol-1at the environmental temperature of 12 degree C. The dimensionless air-water partitioning coefficient is calculated to 2*E-7 m3/m3. The HLC shows that volatilisation of Octopriox from aqueous solutions is very low.

Measurements of Octopirox in the Influent and the activated Sludge of two Municipal Sewage Treatment Plants (Hanover and Hildesheim, Germany)

Octopirox in activated sewage sludge as well as in the sewage influent of the municipal treatment plants in Hildesheim and Hanvover and was determined in a series of 4 (Hildesheim) and 2 (Hanover) consecutive days. In addition, fortification tests at different levels were carried out.

The analysis of Octopirox from two series of samples confirmed the presence of Octopirox in both sewage influent and sewage sludge. The concentrations measured for two sewage treatment plants were different. Whereas the sewage influent of STP Hannover had lower concentrations of Octopirox, the concentration in activated sewage sludge was higher compared to STP Hildesheim. Octopirox concentration in raw sewage influent of the municipal sewage treatment plant in Hildesheim was in a range of 0.92 – 1.35 µg/l. The concentration of Octopirox in activated sewage sludge was 3.40 – 4.06 mg/kg dw. For the municipal sewage treatment plant in Hannover Octopirox concentration in the raw sewage influent was in a range of 0.30 – 0.55 µg/L and 4.66 – 5.30 mg/kg dw in activated sewage sludge. Recovery rates of the fortification tests confirm the robustness of the analytical method for the determination of Octopirox in raw sewage influent and activated sewage sludge of municipal sewage treatment plants.Details are described in IUCLID Section 5.5.1.

The measured Sewage influent concentrations measured in two Sewage Treatment Plants (Hanover and Hildesheim, Germany) are by a factor of more than 5 lower than estimated by the Exposure Modelling Program EUSES 2.1. The concentrations of Octopirox in the activated Sludge of the STPs are by a factor of more than 6 lower than estimated by EUSES 2.1. One possible explantion could be that Octopirox may have a lower use rate in the area where these STPs are located (compare the Section 9 for estimated Exposure data).

Monitoring data

The analysis of Octopirox from two series of samples confirmed the presence of Octopirox in both sewage influent and sewage sludge. The concentrations measured for two sewage treatment plants were different. Whereas the sewage influent of STP Hannover had lower concentrations of Octopirox, the concentration in activated sewage sludge was higher compared to STP Hildesheim. Octopirox concentration in raw sewage influent of the municipal sewage treatment plant in Hildesheim was in a range of 0.92 – 1.35 µg/l. The concentration of Octopirox in activated sewage sludge was 3.40 – 4.06 mg/kg dw. For the municipal sewage treatment plant in Hannover Octopirox concentration in the raw sewage influent was in a range of 0.30 – 0.55 µg/L and 4.66 – 5.30 mg/kg dw in activated sewage sludge. Recovery rates of the fortification tests confirm the robustness of the analytical method for the determination of Octopirox in raw sewage influent and activated sewage sludge of municipal sewage treatment plants.