Hexan-1-ol

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Remarks:

Value estimated based on findings for similar substances (other Category members) in reliable studies.

Justification for type of information:

Please refer to attached justification documents

Qualifier:

no guideline required

Principles of method if other than guideline:

Method: calculated (QSAR)

GLP compliance:

not specified

Analytical monitoring:

not required

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

other: calculated

Water media type:

freshwater

Limit test:

no

Remarks on exposure duration:

not exposure data

Reference substance (positive control):

not required

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

>= 6.8 - <= 13 mg/L

Nominal / measured:

nominal

Conc. based on:

other: (Q)SAR

Basis for effect:

other: reproduction

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

>= 2.56 - <= 6.24 mg/L

Conc. based on:

other: (Q)SAR

Basis for effect:

mortality

Remarks on result:

other: effect concentration range based on initial mean (lowest EC10) to total mean concentrations (highest EC10) and a log Kow of 2.03

Duration:

21 d

Dose descriptor:

EC10

Effect conc.:

>= 3.59 - <= 16.81 mg/L

Conc. based on:

other: (Q)SAR

Basis for effect:

reproduction

Remarks on result:

other: effect concentration range based on initial mean (lowest EC10) to total mean concentrations (highest EC10) and a log Kow of 2.03

Validity criteria fulfilled:

not applicable

Conclusions:

The 21 day chronic NOEC of Daphnia magna has been calculated (QSAR) to lie in the range of 6.8 - 13.0 mg/L based on reproduction.

Description of key information

(21 d) EC₁₀ 2.56 - 6.24 based on mortality of Daphnia magna (QSAR)

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

2.56 mg/L

Additional information

No measured data are available for long-term toxicity of Hexan-1-ol to aquatic invertebrates.

Instead Quantitative structure-activity relationships ((Q)SAR’s) for estimating EC₁₀ based on mortality and reproduction, as well as NOEC_reproduction have been developed in Annex X of the Aliphatic Alcohols SIAR (2006) and in Schäfers et al.(2009). They are also described in PFA report PFA.197.024.001 (2010). It is possible to apply these relationships to predict long-term toxicity endpoints for other members of the Category.

A 21 day chronic toxicity to Daphnia magna EC₁₀ has been calculated (QSAR) to lie in the range of 2.56 -  6.24 mg/L based on mortality. The lowest EC₁₀ in the range is based on initial mean measured concentration and is used for the calculation of the PNECaquatic.

A 21 day chronic toxicity to Daphnia magna EC₁₀ has been calculated (QSAR) to lie in the range of 3.59 -  16.81 mg/L based on reproduction.

A 21 day chronic toxicity to Daphnia magna NOEC has been calculated (QSAR) to lie in the range of 6.8 - 13.0 mg/L based on reproduction.

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

Linear LCAAs

Data of an acceptable quality are available for 21-day reproduction studies with Daphnia magna for the single carbon chain length LCAAs 1-octanol (Kuhn et al., 1989), 1-decanol, 1-dodecanol, 1-tetradecanol, 1-pentadecanol (Fraunhofer Institute, 2005a-d respectively), pentadecanol branched (ABC 1999a) and octadecanol branched (ABC 1999c). The data were obtained generally in accordance with standard test guideline OECD 211. However some modifications to the normal guideline procedures were necessary to reduce losses of test substances due to the extensive and rapid biodegradation of the LCAAs. The following changes to typical protocols were therefore adopted to enable the performance of high-quality and meaningful studies:

 

• Vessels were closed, to reduce entry of bacteria from the atmosphere;
• Gentle aeration of test vessels was required as degradative losses of LCAAs resulted in unacceptably low dissolved oxygen concentrations;
• Test solution renewals were made daily, with confirmatory analysis on both renewed and initial test solutions;
• Static renewal was determined to be the best exposure regime for long chain aliphatic alcohols as this reduced the transfer of LCAAs -degrading or consuming microbes (as compared to flow-through systems, where it becomes increasingly difficult to discourage acclimation and bio film formation; see Brixham Environmental Laboratory, AstraZeneca, 2004);
• Saturated alcohol stock solutions were prepared daily for each test concentration. This involved a detailed preparatory method to reduce the possibility of insoluble material being present in the tests (Fraunhofer Institute, 2005a, b);
• Daphnia magna were carefully rinsed with each daily transfer to reduce bacterial cross over to fresh exposure solutions. As Daphnia magna grow in size, this becomes less effective; and,
• Dilution water and test vessels were autoclaved prior to use each time (Fraunhofer Institute, 2005a, b, c, d).

 

Algae have been found to metabolize LCAAs and this is an unavoidable occurrence in long-term studies with Daphnia magna fed with algae. No modifications could be made to counter this without conducting further research into an alternative diet.

 

In spite of the guideline modifications significant losses of test substance still occurred. It was therefore necessary to report the results both in terms of the mean of the measured concentrations in the fresh media and the mean of the measured concentrations in the fresh and old media. The test substance renewal interval was 24 hours. Survival and reproduction endpoints have been summarised using standard statistical techniques. Conclusions for each test are presented as both NOEC and EC₁₀. The 1-octanol and 1-octadecanol study are reliability 2, valid with restrictions; the other studies are reliability 1.

 

The effect of LCAAs on Daphnia magna survival is generally less sensitive than the effect on reproduction. A pattern of increased toxicity with increasing chain length is also apparent. In the octanol study, the most sensitive and only reported effect was on time to first brood release which occurred at 1000 µg/L (nominal concentration). For comparison of results across chain lengths and structure activity models the response for survival and reproduction was assumed to be equal to the effect on time to first brood.

 

The data indicates that for survival and reproduction, the NOEC and EC₁₀ values increase from C14 to C15. This is almost certainly due to exceeding the limit of water solubility as would be expected from conventional toxicological theory (Rufli et al. 1998). Under these circumstances a more accurate interpretation of the results might be obtained by setting the exposure to the solubility of the substance (i.e. 49 µg/L). This has the effect of lowering the toxicity values but they are still higher than those for the C14 substance. This pattern is not in keeping with the trend of reducing short-term toxicity values (i.e. higher toxicity) observed between the C8 and C14 alcohols. Similarly, the NOEC identified for C18 is a limit value of >980 µg/L but a lower value would have been obtained if a lower loading had been tested. A more accurate NOEC would therefore be obtained by expressing it as greater than the water solubility of the test substance, which is 10 µg/L. This statement is supported by data on C15 and C15 branched, where the NOEC was not achieved at the solubility limit.

 

It must be appreciated that significant uncertainty exists in identifying the true exposure concentrations in the region of the water solubility of a substance. The water solubility values of the LCAAs category decrease with increasing chain length (see section 1.4 for further details.). In a review of aquatic toxicity testing of sparingly soluble compounds Rufli et al. (1998) point out that interpretation of toxicity responses observed above the solubility limit is aggravated by artefacts and that testing should only occur at or below the limit. For LCAAs with carbon numbers greater than C15 there are significant experimental difficulties in producing, maintaining and quantifying exposures of the test substance due to progressively lower solubility, while exceptionally rapid biodegradability would remain unchanged. This explains why there are no data for such substances.

 

However, based on the trends observed in the available data, it is expected that for linear LCAAs with carbon numbers ≥C15 the NOEC for long-term effects on mortality and reproduction would be above the solubility limit (Schäfers et al. 2009).

 

Multi-constituent LCAAs

No measured data are available for multi-constituent substances of different carbon chain length LCAAs.

 

References:

ABC Laboratories (1999a). Chronic toxicity of PMN P98-960 during the complete life-cycle of Daphnia magna under flow-through test conditions. ABC Study No. 45414. Oct.13 1999. ABC Laboratories Inc. 7200 E. ABC Lane, Columbia, Missouri 65202.

 

ABC Laboratories (1999c). Chronic toxicity of PMN P98-963 during the complete life-cycle of Daphnia magna under flow-through test conditions. ABC Study No.45658. Oct.13 1999. ABC Laboratories Inc. 7200 E. ABC Lane, Columbia, Missouri 65202.

 

Kuhn, R., Pattard, M., Pernak, K., and Winter, A. (1989). Results of the harmful effects of water pollutants to Daphnia magna in the 21 day reproduction test.  Wat. Res. 23(4): 501-510.

 

Rufli, H., P. R. Fisk, A. E. Girling, J. M. H. King, R. Lange, X. Lejeune, N. Stelter, C. Stevens, P. Suteau, J. Tapp, J. Thus, D. J. Versteeg, H. J. Niessen. 1998. Aquatic toxicity of sparingly soluble, volatile, and unstable substances and interpretation and use of data. Ecotoxicology and Environmental Safety 39 (2):72-77.

 

Fraunhofer Institute, 2005a. Daphnia magna, reproduction test in closed vessels following OECD 211. C10 fatty alcohol. GLP code: SDA-005/4-21. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) 57377 Schmallenberg, Germany.

 

Fraunhofer Institute, 2005b. Daphnia magna, reproduction test in closed vessels following OECD 211. C12 fatty alcohol. GLP code: SDA-001/4-21. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) 57377 Schmallenberg, Germany.

 

Fraunhofer Institute, 2005c. Daphnia magna, reproduction test in closed vessels following OECD 211. C14 fatty alcohol. GLP code: SDA-006/4-21. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) 57377 Schmallenberg, Germany.

 

Fraunhofer Institute, 2005d. Daphnia magna, reproduction test in closed vessels following OECD 211. C15 fatty alcohol. GLP code: SDA-002/4-21. Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) 57377 Schmallenberg, Germany.

 

Schäfers, C. Boshof, U. Jürling, H. Belanger, S.E. Sanderson, H. Dyer, S.D. Nielsen, A.M. Willing, A. Gamon, K. Kasai, Y. Eadsforth, C.V. Fisk, P.R. Girling, A.E., 2009. Environmental properties of long chain aliphatic alcohols. Part 2: Structure-activity relationship for chronic aquatic toxicity of long-chain alcohols. Ecotoxicology and environmental safety. 72(4): 996-1005.