Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl acrylate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Alkyl acrylates and alkyl methacrylates (not branched) are known rapidly to be hydrolyzed by carboxylesterases. Carboxylesterases are widely distributed in nature, and are common in mammalian and fish liver. Many participate in phase I metabolism; the resulting carboxylates are then conjugated by other enzymes to increase solubility and eventually excreted.
Ethylhexyl methacrylate will be hydrolyzed into Ethylhexyl alcohol. Isobornyl acrylate will be hydrolyzed into Isoborneol and acrylic acid.
Rapid metabolism of Ethylhexyl methacrylate was observed in the bioaccumulation study in fish (Fraunhofer 2006) where the first step in metabolism is predicted to be ester hydrolysis into Ethylhexyl alcohol (CAS 104-76-7) and Methacrylic acid (CAS 79-41-4 ). 50 % decrease in test concentration were observed during the first 2 hours of exposure.
Rapid metabolism (2-3 minutes) was also observed in an in vitro non GLP study of Isobornyl acrylate in rats where the first step in metabolism is predicted to be ester hydrolysis into Isoborneol (CAS 124-76-5) and Acrylic acid (CAS 79-10-7 ) (see chapter 7.1 . Toxicokinetic, metabolism and distribution)
In contrary to the above mentioned study with EHMA the in vivo study of metabolism in rats with isobornyl acrylate was specially performed to test the rate of metabolism.
Table: LogKow of the primary metabolites of Ethylhexyl methacrylate and Isobornyl acrylate.

Substance CAS-Nr. LogKow [KOWWIN v1.68]
Ethylhexyl alcohol 104-76-7 2.73
Methacrylic acid 79-41-4 0.99
Isoborneol 124-76-5 2.85
Acrylic acid 79-10-7 0.44

Metabolites with log Kow < 4.5 are not predicted to bioaccumulate in organisms.

2. ANALOGUE APPROACH JUSTIFICATION
Due to the common phase I metabolism with carboxylesterases and common substance groups of the first metabolites which are alkyl alcohols and (meth) acrylates the analog approach for the endpoint bioaccumulation is justified and the assessment of bioaccumulation based on the log Kow of the metabolites is plausible.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 305 (Bioconcentration: Flow-through Fish Test)

Total exposure / uptake duration:

h

Key result

Type:

BCF

Value:

37 dimensionless

Elimination:

yes

Parameter:

DT50

Depuration time (DT):

1.5 h

Elimination:

yes

Parameter:

other: DT95

Depuration time (DT):

6 h

Details on kinetic parameters:

Uptake of 2-EHMA by fish and steady state BCF (BCFss): The steady state is reached at 1.170 mg/kg fish at 0.033 mg/L and 2.758  mg/kg fish at 0.082 mg/L. When calculating the BCFss by dividing the  conservative steady state concentrations in fish by the mean  concentration measured in water for the same sampling dates, the results  are BCFss = 35 at the low treatment concentration BCFss = 34 at the high treatment concentration

Depuration In the depuration phase concentrations in the fish were below LOQ after 16 h. Consequently, only the data for 0, 1 and 4 h were used to calculate the depuration rates. The depuration rates were calculated to be 0.51 and 0.47/h and thus very similar for the low and the high treatment groups, respectively, indicating a depuration half-life of less than 1.5 h and 95 % depuration within approximately 6 hours.

Determination of k1 and BCFk Uptake rates were calculated to be 19.2 and 17.4/h and thus very similar  for the low and the high treatment level, respectively. From the kinetic  rates the BCFk was calculated to be 37.5 and 37.4 for the low and high  treatment group, respectively.

Details on results:

No adverse effects or mortalities were observed during the study.

During the uptake phase, all concentrations in water and fish were above  the LOQ.

After equilibration of the test system, the nominal test concentrations estimated from the non-GLP pre-study of 0.3 and 0.06 mg/L were nearly met. After addition of the fish, the concentration in water in the low  treatment group, rapidly decreased to 50% of nominal during the first 2 h  of exposure. It remained sufficiently constant at a mean measured  concentration of 0.030 mg/L thereafter. In the high treatment, the  concentration in water rapidly decreased to 30% of nominal during the  first 4 h of exposure. It remained sufficiently constant at a mean  measured concentration of 0.082 mg/L thereafter. 

Test item concentrations in water and fish, and ratios between both for  the low and high test concentrations

       time    c_water  [mg/L]   c_fish [mg/kg]    c_fish/
D       h       low    high       low    high      c_water*
0.0     0      0.066   0.378     0       0          0    0
0.04    1      0.049   0.181     1.146   4.607     20   16
0.08    2      0.035°  0.107     1.232°  5.482     29   38
0.17    4      0.028°  0.088     1.072°  3.452     34   35
0.33    8      0.032°  0.081°    1.064°  3.140°    33   39
0.5    12      0.038°  0.081°    1.310°  2.634°    34   33
1.33   32      0.027   0.084°    0.651   2.171°    24   26
2.33   56      0.025   0.082°    0.574   3.085°    23   38
Steady state** 0.033   0.082°    1.170   2.758     35   34
Deviation ***    15%   0%   11%   18%
        
*   For 1 - 4 hours the means of the concentrations of the
    actual and last sample were used
**  Means were calculated from data marked with "°" 
    considered to represent steady state conditions.
BCFs were calculated from these steady state concentrations.
*** Deviation was calculated as half of the range of those 
    data which were regarded as representing the steady
    state.

Conclusions:

Based on read across approach of a bioaacumulation study acc. OECD 305 with Ethylhexyl methacrylate Isobornyl acrylate is not expected to bioaccumulate in organisms due to rapid metabolism.

Executive summary:

No study on bioaccumulation is available with Isobornyl acrylate. The bioaccumulation was assessed based on read across approach with Ethylhexyl methacrylate regarding a common mechanism of ester hydrolyses with carboxylesterases of Isobornyl acrylate and Ethylhexyl methacrylate.

In a valid guideline study according OECD 305 under flow through conditions a BCF of 37 has been found for 2-Ethylhexyl methacrylate, calculated as mean BCFk derived from the two test concentrations. This value is near the range of 34 - 35 calculated for the BCFss.  Low BCF is based on rapid metabolism.     

Description of key information

The log Kow value of isobornyl acrylate indicates a bioaccumulation potential.

However, in the context of established metabolic pathways and bioaccumulation data of related compounds, no relevant bioaccumulation potential to aquatic and sediment organisms is expected.

Additional information

The octanol/water partition coefficient of the of Isobornyl acrylate was measured according HPLC method with log Kow of 4.52. . Log Kow > 4.5, predicts a potential for bioaccumulation. On the contrary, an experimental study (Fraunhofer, 2006) has been carried out on the structural related 2-ethyl hexyl methacrylate (log Kow > 4) to assess the fish bioconcentration of the substance, according to OECD guideline 305. This study demonstrates that a rapid metabolisation occurs, preventing any significant accumulation (BCF = 37). Moreover, for (meth)acrylate esters in general, it was demonstrated that the first metabolic step is hydrolysis to (meth)acrylic acid and the according alcohol catalysed by unspecific carboxyl esterases which are widespread in organs and tissues of metabolic relevance for organisms potentially affected by bioaccumulation.

In conclusion, no relevant bioaccumulation potential to aquatic and sediment organisms is expected for Isobornyl acrylate.