DL-hexane-1,2-diol

Endpoint summary

Additional information

Valid acute toxicity tests are available for three freshwater species from three trophic levels for the test item itself or structurally similar substances: For fish (read-across to 1,2-Pentanediol), invertebrates, algae (read-across to 1,2-Octanediol) and micro-organism. In all three tests no effects/mortality was observed at tested concentrations up to and above 100 mg/L. For read-across justification see below.

In the algae study with 1,2-Octanediol no statistically significant inhibitory effect on the growth of the algae (average growth rate and yield) during the test period of 72 hours up to and including the highest nominal test concentration of 100 mg/L were observed (ErC50 > 100 mg/L; NOEC >= 100 mg/l).

In the static daphnia test with 1,2-Hexanediol itself no immobilized test organisms were observed during the test period of 48 hours.Thus, the test item had no acute toxic effects on Daphnia magna up to the nominal concentration of 110 mg/L under the conditions of the test (EC50 > 110 mg/L; NOEC >= 110 mg/L).

As well in the fish test with 1,2-Pentanediol, where concentrations up to 1000 mg/L were tested, no mortality occurred during the 96 h exposure for all test concentrations and control. Thus, the LC50 was higher than 1000 mg/l, the highest test concentration (LC50 > 1000 mg/L; NOEC >= 1000 mg/L).

Furthermore a valid respiration inhibition test with activated sludge is available. 1,2-Hexanediol showed no statistically significant inhibitory effects on the respiration rate of activated sludge at the highest tested concentration of 1000 mg/L (EC50 > 1000 mg/L; NOEC >= 1000 mg/L).

In summary, 1,2-Hexanediol is not expected having adverse effect on aquatic species of all trophic levels tested and is considered to be of low concern in the aquatic environment. Long term aquatic testing is not required, as in addition 1,2-hexanediol is readily biodegradable and has a low logPow (0.58) indicative of a low bioaccumulation potential.

Hypothesis for the analogue approach from pentane-1,2-diol to hexane-1,2-diol

Both, pentane-1,2-diol and hexane-1,2-diol, are two corresponding members of a homologue series of linear 1,2-alkyldiols, starting with 1,2-propandiol, 1,2-butandiol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, etc. Based on very similar physico-chemical properties, common functional groups (vicinal diol) and common mode of action similar toxicity to fish can be assumed and thus data on 1,2-pentanediol on acute toxicity to fish can be used as surrogate data for 1,2-hexanediol, suitable for read-across and available data on 1,2-octanediol as surrogate data to cover the acute algae toxicity endpoint.

Source Chemical and Target chemical

	Pentane-1,2-diol data as shown in REACH registration dossier on Pentane-1,2-diol)	Hexane-1,2-diol	Octane-1,2-diol
CAS No	5343-92-0	6920-22-5	1117-86-8
EC No	226-285-3	230-029-6	214-254-7
Mol. weight	104.15	118.18	146.23
Smiles code	OC(CCC)CO	OCC(O)CCCC	OCC(O)CCCCCC
Mol. formula	C5H12O2	C6H14O2	C8H18O2
Appearance	Clear colourless liquid	Clear colourless liquid	Colourless powder
Water solubility	Very soluble (1000 g/L)	Fully miscible (>9000 g/L)	Soluble (7.5 g/L)
logPOW	0.06	0.58	1.67 (estimate)
Vapour pressure	1.5 Pa at 20 °C	0.58 Pa at 20 °C	0.28 Pa at 20 °C
Melting point	-40 °C	2 °C	30 °C
Boiling point	209.4 °C at 1 atm	228.3 ° C at 1 atm	267 ° C at 1 atm
Density	0.98 g/cm3 at 20 °C	0.95 g/cm3 at 20 °C	0.93 g/cm3 at 20 °C
Purity	Typically >99 %	Typically >99 %	Typically >99 %
BCF (calc.)	3.162 L/kg ww	3.162 L/kg ww	5.904 L/kg ww
Henry’s law constant	0.031 Pa m³/mol at 25 °C	0.0411 Pa m³/mol at 25 °C	0.0725 Pa m³/mol at 25 °C
Biodegradation	Readily biodegradable 73% within 28d but failing 10d-window in OECD 301E test and inherently biodegradable 95% within 28d in OECD 302B test	Readily biodegradable 83% within 28d in OECD 301B test	Readily biodegradable 85% within 28d in OECD 301F test Readily biodegradable 75% within 28d in OECD 301D test
Acute toxicity to fish	LC50 (96h) >1000 mg/L	gap	LC50(96h) 2.2 – 22 mg/L
Acute toxicity to algae	EC50(72h) 9335 mg/L	gap	NOEC(72h) >100 mg/L
Acute toxicity to daphnia	EC0 (48h) 500 mg/L	EC10 (48h) > 110 mg/L	EC0(48h) 100 mg/L EC50(48h) 176 mg/L
Toxicity to microorganisms	EC50 (17h) > 10000 mg/L	EC50(3h) >1000 mg/L	NOEC 100 mg/L in toxicity control of OECD 301F test

Purity / Impurities

Read across is possible provided that there is no impact of impurities on the ecotoxicological properties of the target and source chemicals. For both, impurities are comparable or not present.

Analogue Approach Justification

- Common functional groups and mode of action

Both source substances, pentane-1,2-diol and octane-1,2-diol are two corresponding members of a homologue series of linear 1,2-alkyldiols, starting with 1,2-propandiol, 1,2-butandiol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, etc. also including the target substance 1,2-hexanediol. Hence, all three substances share a common functional group (vicinal diol, glycol) in a straight chain alkyl structure.

Hence, the target and the source chemicals all three belong to the group of “Basesurface Narcotics” defined as chemicals that are not classified as reactive unspecified, aldehydes, unsaturated alcohols, phenols and anilines, esters and narcotic amines are included in this category being inert chemicals that are not reactive and do not interact with specific receptors in the organisms and thus sharing the same profile (Verhaar H J M, Van Leeuwen C J, Hermens J.L.M. 1992. Classifying environmental pollutants: Part 1. Structure-activity relationships for prediction of aquatic toxicity. Chemosphere [J] 25:471-491).Thus an equivalent mode of action regarding acute aquatic toxicity for both, target and source chemicals, can be assumed. This is further supported when applying the Aquatic toxicity classification by Ecosar where all three belong to the groups of “Neutral Organics”.

In conclusion, it can be anticipated that target and source chemicals, do share a common mode of action based on equivalent functional groups in the molecule (alkyl glycol function).

- Common precursors and breakdown products

Alkyl glycols are stable in aqueous systems and unreactive. Thus, breakdown products in aqueous solutions are not expected. When metabolised by microorganisms, all three (as shown above) do readily biodegrade ultimately to carbon dioxide and water.

- Common physico-chemical properties

As shown above in the table with data on the two source and target substance, the two source chemicals, 1,2-pentanediol and 1,2-octanediol have very similar physico-chemical properties to the target substance 1,2-hexanediol in particular the good water solubility, and potential for bioaccumulation (log KOW 0.06, 0.58 and 1.67, increasing as expected with increasing lipophilicity). In Addition, their vapour pressure is low and also the Henry law constant, indicating the volatilization from the aquatic compartment is expected to be low.

Thus, the physico-chemical properties support a common expected behavior of the three substances in aquatic systems and strongly support a read-across for aquatic toxicity endpoints such as acute toxicity to fish and acute algae toxicity.

- Common behavior in the aquatic environment at different trophic levels

All three substances have been tested for acute toxicity towards daphnia, not exhibiting significant toxicity when tested at 100 mg/L loading rate or above. When tested for toxicity to microorganisms, all three did not show signs of toxicity towards microorganisms and the effect concentrations on bacteria growth have been shown to be >100 mg/L or even higher for all three. Both of the two source chemicals, 1,2-pentanediol and 1,2-octanediol did not show relevant toxicity to algae when tested at 100 mg/L or above and thus significant toxicity to algae is not expected for 1,2-hexanediol too (interpolation). Regards acute fish toxicity, 1,2-pentanediol showed no mortality in an acute fish toxicity study according to OECD 203 at 1000 mg/L and thus the EC50 and EC10 was established at >1000 mg/L in this test, which included analytic monitoring of test concentrations. When 1,2-octanediol was tested for acute toxicity to fish in a range-finding test mortality at 2.2 mg/L was seen and the EC100 was established at 22 mg/L. Thus the EC50 was to be in the range between 2.2 and 22 mg/L. However, no analytical control and no negative control were used in this test and the study was terminated as a new study design (flow-through system) was needed. Thus, considering an interpolation result being in the range of >100 mg/L for 1,2-hexanediol, read-across to 1,2-pentanediol for acute fish toxicity appears more appropriate in light of the closer similarity of 1,2-pentanediol to 1,2-hexanediol regards to molecular weight, solubility, log POW and aggregate state (1,2-octanediol is solid at room temperature).

In conclusion it can be stated, that the read-across from 1,2-penatediol and 1,2-octanediol to 1,2-hexanediol for acute toxicity to fish and algae is supported by appropriate findings in tests using other trophic levels and microorganisms.

All three substances do show very similar physico-chemical properties (see above) in particular regards water solubility (soluble – very soluble with water) and low log POW values and show a slight trend regards increasing bioaccumulation potential and decreasing water solubility as the alky chain becomes more dominant (increasing lipophilicity); consequently, similar availability to aquatic species such as fish and algae can be assumed, in particular when comparing 1,2-pentanediol and 1,2-hexanediol.

Conclusion on bioavailability and metabolism of source and target substance

As discussed above, both source substance (1,2-pentanediol and 1,2-octanediol) and the target substance 1,2-hexanediol do share identical functional groups and only differ structurally in the chain length of the alkyl moiety. Physico-chemical properties and mode of action in aquatic biota are comparable supporting a read-across for acute fish toxicity which is further supported by equivalent findings for acute daphnia and microorganism toxicity.

As a consequence it can be reasonably assumed that acute data on fish toxicity of 1,2-pentanediol can be used to predict acute fish toxicity of 1,2-hexanediol more appropriately that data from 1,2ocatnediol (see above) and acute toxicity to algae can be read-across from 1,2-ocatendiol supported by interpolation. Consequently, such a read-across approach is valid and justified.

Conclusion on Classification and Labelling / Risk and Hazard Assessment

Data for acute fish toxicity of pentane-1,2-diol are fully reliable and as used for read-across were reduced in reliability to Klimisch score 2 and the same applies to the acute algae toxicity on 1,2-octanediol. Their results are adequate for deciding upon classification and labeling as well as for concluding upon hazard and risk assessment for these pathways as in both studies at the highest tested concentration no toxicity was observed and the doses tested were above classification thresholds.