Reaction mass of Benzenepropanal, 4-ethyl-α,α-dimethyl- and 3-(2-ethylphenyl)-2,2-dimethylpropanal

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1st August 2001 - 20th November 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Daphnia magna

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

2.5mmol/l (=250 mg/l Ca)

Test temperature:

20-22oC

pH:

7.9 +/-0.3

Dissolved oxygen:

Saturated with oxygen

Conductivity:

Alkalinity: 0.9 mmol

Nominal and measured concentrations:

Nominal concentrations were: 0.038, 0.12, 0.38, 1.2 abd 3.8 mg/l.
Measured concentrations were: for nominal concentrations 1.2 and 3.8 mg/l were 75-81% at the start which decreased to 29-58% before renewal based on test media without food. It was shown that in the media with food the concentrations dropped below the LoQ and therefore it was assumed that the substance adsorbed to the food particles.

Reference substance (positive control):

not specified

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.7 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other:

Remarks:

The sum of the sixfold geometric mean of the two day period (day 12-14) plus the threefold geometric mean of the three days period (day 16-19) divided by 9.

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

1.7 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other:

Remarks:

The sum of the sixfold geometric mean of the two day period (day 12-14) plus the threefold geometric mean of the three days period (day 16-19) divided by 9.

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

>= 2.6 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

immobilisation

Remarks on result:

other:

Remarks:

The sum of the sixfold geometric mean of the two day period (day 12-14) plus the threefold geometric mean of the three days period (day 16-19) divided by 9.

Table: Number of surviving test animals. Concentrations are expressed in nominal concentration. The nominal concentrations 1.2 and 3.8 mg/l result in 0.71 and 2.6 mg/l actual exposure concentrations.

Exposure days	Control	0.038 mg/l	0.12 mg/l	0.38 mg/l	1.2 mg/l	3.8 mg/l
0	10	10	10	10	10	10
1	10	10	10	10	10	10
2	10	10	10	10	10	10
5	10	10	10	10	10	9
7	10	10	10	10	10	9
9	10	9	9	9	10	9
12	10	9	9	9	10	9
14	10	9	9	9	10	9
16	9	9	9	9	10	9
19	9	9	9	9	10	9
21	8	9	9	9	10	9
% Surviving on Day 21	80	90	90	90	100	90

Table: Total number of alive, young daphnids reproduced by all adults (cumulative values). Concentrations are expressed in nominal concentrations.

The nominal concentrations 1.2 and 3.8 mg/l result in 0.71 and 2.6 mg/l actual exposure concentrations.

Exposure day	Control	0.038 mg/l	0.12 mg/l	0.38 mg/l	1.2 mg/l	3.8 mg/l
0	0	0	0	0	0	0
1	0	0	0	0	0	0
2	0	0	0	0	0	0
5	0	0	0	0	0	9
7	0	0	0	0	0	9
9	110	69	71	105	109	0
12	214	182	156	219	226	18
14	214	227	178	219	226	20
16	431	403	385	407	447	43
19	635	584	550	539	599	52
21	635	648	589	539	625	80
% of control (based on the last exposure day)	100%	102.0	92.8	84.9	98.4	12.6

Table: The number of alive offspring reproduced per surviving adult within 21 days of exposure. Concentrations are expressed in nominal concentrations.

The nominal concentrations 1.2 and 3.8 mg/l result in 0.71 and 2.6 mg/l actual exposure concentrations.

Replicate number	Control	0.038 mg/l	0.12 mg/l	0.38 mg/l	1.2 mg/l	3.8 mg/l
0	71	70	63	50	73	24
1	*	71	70	40	61	3
2	60	71	78	71	54	17
4	52	67	65	74	79	16
5	72	86	*	42	68	9
6	70	85	58	59	64	0
7	75	69	73	*	74	0
8	68	72	59	78	54	6
9	69	54	62	50	53	*
10	*	*	61	74	45	5
Mean +/- SD	67.1 (+/- 7.5)	71.7 (+/-9.5)	65.4 (+/- 6.8)	59.8 (+/-14.8)	62.5 (+/- 11.0)	8.9 (+/-8.4)
N	8	9	9	9	10	9
CV%	11.2	13.3	10.4	24.8	17.6	94.2
STAT	n.s.	n.s.	n.s.	n.s.	n.s.	s

CV%: coefficient of variation in %; STAT: results of a William-test with the mean values of alive offspring (one-sided smaller, alpha = 0.05); n.s.: not significant; s: significant; * test animal died during the test period.

Validity criteria fulfilled:

yes

Remarks:

Temperature, pH and dissolved oxygen were in the required range. The surviving adults were 80% in the control.

Conclusions:

The reproductive NOEC in the long-term Daphnia study (OECD TG 211) is 0.71 mg/l based on geometric mean measured concentrations.

Executive summary:

Florhydral is tested in a long-term Daphnia test according to OECD TG 211. The nominal concentrations were 0.038, 0.12, 0.38, 1.2 and 3.8 mg/l. The measured concentrations were lower than nominal and the concentrations in the test vessels with food were lower than without food. Therefore it was assumed that the substance adsorbed to the Daphnia feed and the exposure to Daphnia was via the water phase and via feed. In view of these two exposure routes it was considered justified to calculate the concentrations from the vessels without feed. The concentrations were measured as follows: The sum of the sixfold geometric mean of the two day period (day 12-14) plus the threefold geometric mean of the three days period (day 16-19) divided by 9. The nominal 1.2 and 3.8 mg/l were actual 0.71 and 2.6 mg/l. respectively. Temperature (20 -22oC), pH (7.5 -7.9) and dissolved oxygen (at least 8 mg/l) were in the set boundaries. Survival was not affected in the adult animals. At all concentration survival was >=80% (the 80% survival was found in the control). The total number of juveniles produced for all Daphnia at a certain concentration was not affected up to 0.71 mg/l (nominal 1.2) and resulted in 80 -100% of the number that were produced in the control. At the highest concentration 2.6 the total number was decreased to 12.6%. The number of juveniles per adult was similar (60 -70) in all concentrations up to 0.71 mg/l and decreased to 9 at the highest concentration: 2.6 mg/l. Therefore the NOEC for reproduction (most sensitive endpoint) was 0.71 mg/l. The EC50 for reproduction was 1.7 mg/l.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

other: Read across from Florhydral

Adequacy of study:

key study

Study period:

January 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: information retrieved from read across

Justification for type of information:

Information is based on the analogue Florhydral. The read across justification and the derived acute chronic ratio is presented in the Long-term toxicity to aquatic invertebrates, the files are also attached there.

Reason / purpose for cross-reference:

read-across source

Guideline:

other: The acute chronic ratio from an analogue is used

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.3 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other: The NOEC is derived based on the acute / chronic ratio found for Florhydral

Details on results:

Floralozone and Florhydral have a similar backbone and similar functional group and therefore the acute chronic ratio for Daphnia of Florhydral can be applied to Floralozone. The EC50 Daphnia of Florhydral is 2 and its long-term NOEC is 0.7 mg/l resulting in acute chronic ratio of 2.9. Floralozone has an EC50 Daphnia of 0.87 mg/l and dividing this value with the acute chronic ratio the long-term NOEC for Floralozone is 0.3 mg/l.

Validity criteria fulfilled:

yes

Remarks:

Read across information is reliable and adequately documented

Conclusions:

Floralozone and Florhydral have a similar backbone and similar functional group and therefore the acute chronic ratio for Daphnia of Florhydral can be applied to Floralozone. The EC50 Daphnia of Florhydral is 2 and its long-term NOEC is 0.7 mg/l resulting in acute chronic ratio of 2.9. Floralozone has an EC50 Daphnia of 0.87 mg/l and dividing this value with the acute chronic ratio the long-term NOEC for Floralozone is 0.3 mg/l.

Description of key information

Floralozone has a long-term Daphnia NOEC of 0.3 mg/l based on the acute chronic ratio found for Florhydral, which is an analogue of Floralozone. Florhydral acute chronic ratio is derived from the results from the OECD TG 202 (acute) and 211 (long-term), respectively.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.3 mg/L

Additional information

For Floralozone the long-term Daphnia can be derived from the acute chronic ratio form Florhydral. The acute Daphnia toxicity is presented in the short-term section. The long-term Daphnia toxicity of Florhydral will be presented first. Thereafter the justification for read across and using the acute chronic ratio will be presented.

Florhydral long-term Daphnia study

Florhydral is tested in a long-term Daphnia test according to OECD TG 211. The nominal concentrations were 0.038, 0.12, 0.38, 1.2 and 3.8 mg/l. The measured concentrations were lower than nominal and the concentrations in the test vessels with food were lower than without food. Therefore it was assumed that the substance adsorbed to the Daphnia feed and the exposure to Daphnia was via the water phase and via feed. In view of these two exposure routes it was considered justified to calculate the concentrations from the vessels without feed. The concentrations were measured as follows: The sum of the sixfold geometric mean of the two day period (day 12-14) plus the threefold geometric mean of the three days period (day 16-19) divided by 9. The nominal 1.2 and 3.8 mg/l were actual 0.71 and 2.6 mg/l. respectively. Temperature (20 -22oC), pH (7.5 -7.9) and dissolved oxygen (at least 8 mg/l) were in the set boundaries. Survival was not affected in the adult animals. At all concentration survival was >=80% (the 80% survival was found in the control). The total number of juveniles produced for all Daphnia at a certain concentration was not affected up to 0.71 mg/l (nominal 1.2) and resulted in 80 -100% of the number that were produced in the control. At the highest concentration 2.6 the total number was decreased to 12.6%. The number of juveniles per adult was similar (60 -70) in all concentrations up to 0.71 mg/l and decreased to 9 at the highest concentration: 2.6 mg/l. Therefore the NOEC for reproduction (most sensitive endpoint) was 0.71 mg/l. The EC50 for reproduction was 1.7 mg/l.

Floralozone (Cas no 67634-15-5) and its long-term Daphnia toxicity using the Acute Chronic ratio of the analogue Florhydral (125109-85-5)

Introduction and hypothesis for the analogue approach

Floralozone is aphenyl-propyl aldehyde. For this substance acute aquatic toxicity information is available and chronic algae information. Further long-term Daphnia information is needed to present safe use for the terrestrial environment using the Equilibrium Partition Method. In accordance with Article 13 of REACH,lacking information can be generated by means of applying alternative methods such asin vitrotests, QSARs, grouping and read-across. For assessing the long term Daphnia toxicity for Floralozone the analogue approach and the analogue acute chronic ratio is selected.

Hypothesis: The long term Daphnia NOEC for Floralozone can be derived from its acute Daphnia value (0.87 mg/l) and dividing this value by the Daphnia acute chronic ratio of Florhydral (2.9), resulting in a NOEC for Floralozone of 0.3 mg/l.

Available experimental information:The target Floralozone and the source Florhydral both have aquatic toxicity for algae, Daphnia and fish according to OECD TG 201, 202 and 203, respectively. The acute Daphnia EC50s of Floralozone and Florhydral are 0.87 and 2 mg/l, respectively. Florhydral (source) also has a NOEC from a long-term Daphnia according to OECD TG 211, Kl1 of 0.7 mg/l. The acute chronic ratio of Florhydral is 2.9 (EC50 of 2/NOEC of 0.7 mg/l) and therefore the NOEC of Floralozone is 0.3 mg/l (EC50 / 2.9 (acute chronic ratio of Florhydral).

Target chemical and source chemical(s)

Chemical structures of the target chemical and the source chemical are shown in the data matrix. Also physico-chemical properties thought relevant for aquatic toxicity are listed in there.

Purity / Impurities

The purity and impurities of the target chemical do not indicate other aquatic toxic potential and/or the acute/chronic ratio. The impurities are all below < 10%.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.

Analogue selection:Florhydral is selected as an analogue because of similarities in chemical structure for which long-term Daphna information is available.

Structural similarities and differences:The target and the source chemicals both have a phenyl propyl backbone to which an aldehyde functional group is attached. Floralozone has a quaternary carbon to which the aldehyde is attached while Florhydral has a secondary carbon at the same spot. The phenyl group is substituted with an ethyl group in Floralozone at the para or ortho-position, while Florhydral has an isopropyl group attached to the phenyl group at the meta-position.

Bioavailability:The source chemical Floralozone likely has a slightly higher bioavailability compared to Florhydral based on the measured log Kow (4 and 3.1, respectively) and the slightly lower acute Daphnia toxicity value (0.87 and 2 mg/l). The water solubility in the aquatic toxicity test of Floralozone is also somewhat lower compared to Florhydral because for Floralozone the algae and fish toxicity are above the water solubility while for Florhydral these toxicity values are between 1-10 mg/l. Other characteristics are very similar. The molecular weight of both substances is 190. They are both liquids. Floralozone and Florhydral have similar vapour pressures 0.43 and 0.65, respectively. The position of the Floralozone’s ethyl group on the ring versus the isopropyl group of Florhydral does not change the bioavailability significantly (similar log Kow are predicted in ECOSAR: 3.9).

Mode of Action:Floralozone and Florhydral have a similar backbone and similar aldehyde functional group, which will present a similar mode of action. The quaternary carbon of Floralozone versus the secondary carbon attached at the aldehyde group is not expected to significantly change the reactivity of the aldehyde. This is supported when calculating the pKa of the respective acids of these substances. Floralozone has a pKa of 4.62 and Florhydral of 4.64 (SPARC calculations). The difference in log Kow between these two cannot fully explain the slightly higher toxicity of Floralozone (0.87 versus 2 mg/l). Therefore it is considered more appropriate to apply the acute chronic ratio found for Florhydral to Floralozone.

Uncertainty of the prediction: There are two acute Daphnia results for Florhydral. One from 1991 and one from 2016: 5.48 and 2 mg/l, respectively. Limited analytics are done in the first study and therefore the second study with an EC50 of 2 mg/l better reflects the actual EC50. This latter EC50 of Florhydral is also closer to the 0.87 mg/l of Floralozone. There are no other remaining uncertainties.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the data matrix below).

Conclusions per endpoint

When using read across the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. Floralozone and Florhydral have a similar backbone and similar functional group and therefore the acute chronic ratio for Daphnia of Florhydral can be applied to Floralozone. The EC50 Daphnia of Florhydral is 2 and its long-term NOEC is 0.7 mg/l resulting in acute chronic ratio of 2.9. Floralozone has an EC50 Daphnia of 0.87 mg/l and dividing this value with the acute chronic ratio the long-term NOEC for Floralozone is 0.3 mg/l.

Final conclusion: Floralozone has a long-term Daphnia NOEC of 0.3 mg/l.

 

Data matrix:        Characteristics of Floralozone and Florhydral for assessing the long-term Daphnia NOEC for Floralozone using the acute chronic ratio of Florhydral                                                                                                                                                                                                                                         

Common names	Floralozone	Florhydral
	Target	Source
Chemical structures
REACH registration	Registered for 2018 deadline	Registered
Cas no of the main isomer Cas no of the minor isomer	67634-15-5 67634-14-4	125109-85-5
EINECS	266-819-2 266-819-7	412-050-4
Molecular weight	190	190
Physico-chemical data	IFF measured	ECHA dissemination site
Physical state	Liquid	Liquid
Vapour pressure Pa (measured)	0.43	0.65
Water solubility mg/l (measured)	40	40
Log Kow (measured)	4	3.1
Log Kow (calculated - ECOSAR)
Acute Aquatic toxicity
Fish mg/l	> 0.7 (OECD TG 203)	1.15 (OECD TG 203)
Daphnia mg/l	0.87 (OECD TG 202)	2.0* (OECD TG 202)
Alga mg/l	>=1.2 (OECD TG 201)	11/8.4 (OECD TG 201)
Long-term Aquatic toxicity
Fish mg/l	No data available)	No data available
Daphnia mg/l	0.3 Read across and acute chronic ratio (2/0.7)	0.7 OECD TG 211
Algae mg/l	> =1.2	3.2

* On the ECHA website a value of 5.48 is presented from a 1991 study (ECHA dissemination site). The EC50 of a 2016 study is used here.