4-(4-isopropoxyphenylsulfonyl)phenol

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:

from 1993-03-01 to 1993-12-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD 202: Daphnia sp.; Acute Immobilisation Test and Reproduction Test, Part 2

Version / remarks:

04 April 1984

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

Unfiltered samples (20 mL) of aqueous test media were diluted to equate HPLC mobile phase to within the nominal concentration range of 0.1 to 10 mg/L. The concentrations of D-8 in the diluted samples were then determined by high performance liquid chromatography using a spectrophotometric detector.

Vehicle:

no

Details on test solutions:

Two aqueous stock preparations of D-8 were prepared at nominal concentrations of 5 and 15 mg/L. Test material was directly added to the dilution water. As the 15 mg/L concentration is near the aqueous solubility limit of D-8 (19.7 mg/L), the stock solutions were shaken overnight to ensure complete dissolution. These stock solutions were used directly at the two highest test levels. The 5 mg/L stock solution was then diluted with water to provide the three lower test levels (0.15 to 1.5 mg/L).

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Strain/clone: genetically homogeneous
- Source: University of Sheffield; England
- Age of parental stock:
- Feeding during test
- Food type: Algae (Chlorella vulgaris) and baker's yeast
- Amount: algae density: 2 to 8E5 cells per mL; yeast: suspension with a nominal concentration of 0.04 to 0.05 mg/L
- Frequency: five times each week

ACCLIMATION
- Acclimation period: not indicated
- Acclimation conditions: not indicated

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

45 to 59 mg/L as CaCO3

Test temperature:

20.0 ± 0.7 °C

pH:

7.1 to 8.2

Dissolved oxygen:

95 - 103 % ASV (ASV = Air Saturation Value)

Nominal and measured concentrations:

Nominal: 0.15; 0.5; 1.5; 5 and 15 mg/L
Measured: 0.139; 0.492; 1.45; 5.04 and 14.8 mg/L

Details on test conditions:

Groups of forty Daphnia were exposed to D-8 at nominal concentrations of 0.15, 0.5, 1,5, 5 and 15 mg/L. Five Daphnia were placed into each of the test vessels. Test media were renewed three times each week. A control group of Daphnia was exposed to dilution water alone. The test was conducted at 20 ± 0.7 °C in treated tap water of hardness 45 to 59 mg/L as CaCO3 at pH 7.1 to 8.2. At all concentrations, test media were clear and colourless on days of preparation. Exposure levels were monitored by HPLC method. The numbers of mobile, immobile and dead parental Daphnia were recorded each day of the test and the numbers of juveniles produced were counted three times each week.

A 48-hour range finding toxicity test showed an EC50 between 10 and 16 mg/L. The limit of water solubility of D-8 is 19.7 mg/L.

Reference substance (positive control):

no

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.492 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks:

mean cumulative number of juveniles per surviving adult

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.139 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks:

total number of juveniles per vessel

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.139 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Duration:

21 d

Dose descriptor:

LC50

Effect conc.:

2.7 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: 95 % CI: 1.80 - 3.65 mg/L

Duration:

14 d

Dose descriptor:

LC50

Effect conc.:

5.4 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: approximate values

Duration:

7 d

Dose descriptor:

LC50

Effect conc.:

7.4 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: 95 % CI: 5.91 - 8.89 mg/L

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

10.5 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: 95 % CI: 9.02 - 12.5 mg/L

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

13.4 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: approximate values

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

1.9 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks:

total number of juveniles produced at each meas. concentration

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

2.94 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks:

mean cumulative number of juveniles per adult

Details on results:

Mortality of parental Daphnia:
After 21 days, 17.5 % of the parental control Daphnia had died. In groups exposed to D-8, mortality was concentration-related, ranging from 22.5 % at the lowest exposure level (0.139 mg/L) to 100 % at the highest (14.8 mg/L).
Juvenile production:
On Day 5, gravid Daphnia were observed in all of the control vessels, in all of the test vessels at 0.139, 0.492 and 1.45 mg/L and in two of the vessels at 5.04 mg/L. After eight days, the majority of the Daphnia in the control vessels and in the test vessels up to and including 1.45 mg/L were gravid, and at 5.04 mg/L each vessel contained some gravid Daphnia. No gravid Daphnia were observed at 14.8 mg/L during the test.

Reported statistics and error estimates:

Median lethal concentrations (LC50's) for parental generation were calculated by appropriate statistical methods (binomial, moving average or probit). Median effect concentrations (EC50's) for reproduction were similarly calculated using the total number of juveniles produced at each concentration, and the cumulative number of juveniles per adult.
The numbers of dead parental Daphnia, the total number of juveniles and the mean number of juveniles produced per adult in the control group were compared with those in the test groups, by Dunnett's multi-comparison test which uses a multiple t-test with a common estimate of experimental error.

Table 1. Analytical determination of D-8

Sampling time, days	Nominal D-8 concentrations, mg/L
	0.15	0.5	1.5	5.0	15.0
Untreated samples
5 (new)	0.154, 0.154 (103)	0.531, 0.539 (107)	1.68, 1.56 (108)	5.20, 5.46 (107)	14.8, 14.8 (99)
8 (old)	0.143, 0.146 (96)	0.498, 0.499 (100)	1.52, 1.53 (102)	5.12, 5.15 (103)	14.9, 14.9 (99)
8 (new)	0.144, 0.140 (95)	0.510, 0.500 (101)	1.49, 1.52 (100)	5.00, 5.03 (100)	14.7, 14.8 (98)
11 (old)	0.133, 0.129 (87)	0.474, 0.448 (92)	1.40, 1.38 (93)	5.06, 4.90 (100)	14.6, 14.6 (97)
15 (new)	0.133, 0.150 (94)	0.491, 0.494 (99)	1.34, 1.35 (90)	5.03, 5.01 (100)	-
18 (old)	0.123, 0.124 (82)	0.456, 0.460 (92)	1.28, 1.29 (86)	4.71, 4.76 (95)	-
Mean value	0.139 (93)	0.492 (98)	1.45 (97)	5.04 (101)	14.8 (99)
Centrifuged samples
8 (new)	0.137 (91)	0.484 (97)	1.46 (97)	4.96 (99)	14.7 (98)
11 (old)	0.130 (87)	0.464 (93)	1.39 (93)	4.78 (96)	14.3 (95)

Control samples: no D-8 was detected in every measurement of the control samples

(): Mean measured concentrations expressed as percentage of the nominal levels.
-: No analysis was required at the level because all of the parental animals died.

Table 2. Cumulative number of dead parental Daphnia

Observation time (days)	Measured D-8 concentration (mg/L)
	0	0.139	0.492	1.45	5.04	14.8
1	0	0	0	0	0	19
2	0	0	0	0	0	23
3	0	0	0	0	0	23
4	1	0	1	1	2	30
5	1	1	1	1	6	32
6	1	1	1	1	8	35
7	1	1	3	2	11	35
8	1	1	4	3	11	36
9	3	1	5	4	14	36
10	6	4	8	5	16	40
11	6	6	11	7	18	40
12	6	7	13	9	18	40
13	6	9	14	9	18	40
14	6	9	14	9	18	40
15	7	9	16	11	18	40
16	7	9	16	13	18	40
17	7	9	17	15	20	40
18	7	9	17	16	21	40
19	7	9	17	16	21	40
20	7	9	18	18	22	40
21	7	9	18	18	22	40
% dead on day 21	17.5	22.5	45	45	55	100

At the start of the test 40 daphnids were introduced at each concentration.

Table 3. Cumulative number of juveniles produced by parental Daphnia in each control and test vessel

Measured conc. D-8 (mg/L)	Cumulative no. of juveniles produced in each vessel
	8 days	11 days	13 days	15 days	18 days	21 days
Control	32, 47, 49, 45	238, 192, 222, 219	287, 241, 258, 219	448, 395, 379, 365	698, 653, 614, 637	984, 1020, 831, 1028
Total	173	871	1005	1587	2602	3863
0.139	60, 58, 35,76	215, 215, 216, 214	254, 262, 249, 302	422, 360, 406, 442	721, 542, 599, 699	892, 754, 844, 1006
Total	229	860	1067	1630	2561	3496
0.492	89, 115, 81, 45	291, 271, 203, 211	291, 279, 216, 253	446, 450, 362, 382	673, 668, 591, 641	794, 739, 713, 813
Total	330	976	1039	1640	2573	3059
1.45	23, 17, 10, 38	203, 160, 170, 180	254, 194, 269, 275	338, 296, 323, 343	534, 499, 491, 521	676, 725, 575, 649
Total	88	713	992	1300	2045	2625
5.04	0, 0, 0, 0	49, 57, 91, 40	93, 74, 118, 58	154, 105, 144, 100	225, 144, 159, 153	262, 196, 167, 251
Total	0	237	343	503	681	876
14.8	No juveniles were produced
Total

Table 4. Mean cumulative number of juveniles produced per adult in each vessel

Measured conc. D-8 (mg/L)	Mean cumulative no. of juveniles produced per adult
	8 days	11 days	13 days	15 days	18 days	21 days
Control	3.2, 4.7, 5.4, 4.5	23.8, 19.2, 24.6, 21.9	29.9, 24.6, 29.1, 21.9	50.0, 41.7, 44.2, 38.1	81.3, 70.4, 73.6, 72.1	117.1, 111.2, 100.7, 121.0
Mean	4.5	22.4	26.4	43.5	74.4	112.5
0.139	6.0, 5.8, 3.9, 7.6	21.5, 21.5, 24.0, 21.4	26.4, 26.7, 28.7, 30.2	47.4, 40.7, 51.1, 45.8	84.8, 66.7, 78.7, 74.4	106.2, 97.0, 113.7, 108.5
Mean	5.8	22.1	28.0	46.3	76.2	106.4
0.492	9.9, 11.5, 8.1, 4.5	35.2, 27.1, 20.3, 25.3	35.2, 28.1, 22.2, 30.6	66.2, 49.5, 46.5, 49.0	111.6, 85.8, 84.7, 86.0	135.8, 100.0, 105.0, 110.6
Mean	8.5	27.0	29.0	52.8	92.0	112.9
1.45	2.6, 1.7, 1.0, 3.8	22.6, 19.6, 17.0, 18.0	28.3, 24.5, 28.0, 29.9	37.6, 39.1, 35.7, 38.4	59.4, 68.1, 69.3, 60.7	79.7, 100.4, 97.3, 79.0
Mean	2.3	19.3	27.7	37.7	64.4	89.1
5.04	0, 0, 0, 0	6.1, 8.1, 11.4, 6.7	14.9, 10.9, 16.8, 9.7	27.1, 16.1, 22.0, 16.7	41.3, 22.6, 25.0, 25.5	50.6, 31.3, 27.7, 41.8
Mean	0	8.1	13.1	20.5	28.6	37.9
14.8	No juveniles were produced

 

Validity criteria fulfilled:

yes

Conclusions:

D-8 was tested for 21-day juvenile production study in Daphnia magna according to OECD Guideline 202. The 21-day median lethal concentration (LC50) of D-8 to parental Daphnia was calculated to be 2.70 mg/L. The 21-day EC50 values for inhibition of reproduction were 1.90 mg/L based on the total number of juveniles produced at each mean measured concentration, and 2.94 mg/L based on the mean cumulative number of juveniles produced per adult. In conclusion, D-8 significantly affected both the survival of the parental generation and their ability to produce viable juveniles at concentrations above 0.139 mg/L. Therefore, NOEC was determined to be 0.139 mg/L.

Executive summary:

The effect of D-8 on the survival and reproduction of Daphnia magna has been assessed under semi-static exposure conditions over a period of 21 days in accordance with OECD 202, Part 2 (1984). Groups of forty Daphnia were exposed to D-8 at nominal concentrations of 0.15, 0.5, 1.5, 5 and 15 mg/L, selected following a ten-day range finding test. A control group of Daphnia was exposed to dilution water alone. The test was conducted at 20 ± 0.7 °C in treated tap water of hardness 45 to 59 mg/L as CaCO3 at pH 7.1 to 8.2. Exposure levels were monitored by HPLC analysis. The numbers of mobile, immobile and dead parental Daphnia were recorded each day of the test, and the numbers of juveniles produced were counted three times each week.

In groups exposed to D-8, mortality of the parental Daphnia after 21 days ranged from 22.5 % at the lowest level (0.139 mg/L) to 100 % at the highest level (14.8 mg/L). Mortality of the parental control Daphnia after 21 days was 17.5 %.

The 21-day median lethal concentration (LC50) of D-8 to parental Daphnia was calculated to be 2.70 mg/L, with 95 % confidence limits of 1.80 - 3.65 mg/L.

The 21-day EC50 values for inhibition of reproduction were 1.90 mg/L, based on the total number of juveniles produced at each mean measured concentration, and 2.94 mg/L, based on the mean cumulative number of juveniles produced per adult. In conclusion, D-8 significantly affected both the survival of the parental generation and their ability to produce viable juveniles at concentrations above 0.139 mg/L. Therefore, NOEC was determined to be 0.139 mg/L.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Version / remarks:

2012

Deviations:

no

GLP compliance:

no

Analytical monitoring:

yes

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: D. magna
- Feeding during test
- Food type: Chlorella vulgaris (AquaNet, Gyeongnam, Korea)
- Frequency: daily

Test type:

not specified

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

monitored daily

Test temperature:

monitored daily

pH:

monitored daily

Dissolved oxygen:

monitored daily

Salinity:

monitored daily

Conductivity:

monitored daily

Nominal and measured concentrations:

0, 0.06, 0.12, 0.25, 0.5, 1 mg/L (nominal)

Details on test conditions:

TEST SYSTEM
- Renewal rate of test solution: at least three times a week
- No. of organisms per vessel: 10

OTHER TEST CONDITIONS
- Photoperiod: 16:8 h light:dark

EFFECT PARAMETERS MEASURED: survival of parent animal, first day of neonate production, number of neonates per parent animal, number of neonates per brood, and growth

Reference substance (positive control):

no

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

0.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: body length

Validity criteria fulfilled:

not specified

Conclusions:

The NOEC value for reproduction of D-8 in this 21-d chronic toxicity test was 1 mg/L, the highest concentration tested.

Executive summary:

In this study, long-term toxicity tests of D-8 were performed using Daphnia magna. The Daphnia magna (21 d) chronic toxicity tests were conducted as outlined in Organization for Economic Cooperation and Development (OECD) test guidelines 211 (OECD, 2012). For D. magna chronic toxicity tests, 10 neonates per group were exposed to D-8 (0, 0.06, 0.12, 0.25, 0.5, 1 mg/L). The endpoints were survival of parent animal, first day of neonate production, number of neonates per parent animal, number of neonates per brood, and growth. InD. magnaexposed to D-8 for 21 d, no adverse effects of survival and reproduction were observed up to the highest test concentration of 1 mg/L. However, the body length was significantly reduced when exposed to 1 mg/L of D-8. The NOEC value for reproduction of D-8 was 1 mg/L. D-8 was also tested for 7 days in Moina macrocopa, an indigenous species in Asia, in concentrations of 0, 0.01, 0.03, 0.11, 0.33, 1 mg/L. The endpoints were survival of parent animal, first day of neonate production, number of neonates per parent animal, number of neonates per brood. The first day of reproduction was significantly increased at 1 mg/L D-8. The number of young per female, one of the most sensitive endpoints related to the reproduction, was significantly decreased with treatment of 0.3 mg/L of D-8.The NOEC value for reproduction of D-8 was 0.1 mg/L.

Description of key information

D-8 was tested for 21-day juvenile production study in Daphnia magna according to OECD Guideline 202. The 21-day median lethal concentration (LC50) of D-8 to parental Daphnia was calculated to be 2.70 mg/L. The 21-day EC50 values for inhibition of reproduction were 1.90 mg/L based on the total number of juveniles produced at each mean measured concentration, and 2.94 mg/L based on the mean cumulative number of juveniles produced per adult. In conclusion, D-8 significantly affected both the survival of the parental generation and their ability to produce viable juveniles at concentrations above 0.139 mg/L. Therefore, NOEC was determined to be 0.139 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.139 mg/L

Additional information

The effect of D-8 on the survival and reproduction of Daphnia magna has been assessed under semi-static exposure conditions over a period of 21 days in accordance with OECD 202, Part 2 (1984). Groups of forty Daphnia were exposed to D-8 at nominal concentrations of 0.15, 0.5, 1.5, 5 and 15 mg/L, selected following a ten-day range finding test. A control group of Daphnia was exposed to dilution water alone. The test was conducted at 20 ± 0.7 °C in treated tap water of hardness 45 to 59 mg/L as CaCO3 at pH 7.1 to 8.2. Exposure levels were monitored by HPLC analysis. The numbers of mobile, immobile and dead parental Daphnia were recorded each day of the test, and the numbers of juveniles produced were counted three times each week.

In groups exposed to D-8, mortality of the parental Daphnia after 21 days ranged from 22.5 % at the lowest level (0.139 mg/L) to 100 % at the highest level (14.8 mg/L). Mortality of the parental control Daphnia after 21 days was 17.5 %.

The 21-day median lethal concentration (LC50) of D-8 to parental Daphnia was calculated to be 2.70 mg/L, with 95 % confidence limits of 1.80 - 3.65 mg/L.

The 21-day EC50 values for inhibition of reproduction were 1.90 mg/L, based on the total number of juveniles produced at each mean measured concentration, and 2.94 mg/L, based on the mean cumulative number of juveniles produced per adult. In conclusion, D-8 significantly affected both the survival of the parental generation and their ability to produce viable juveniles at concentrations above 0.139 mg/L. Therefore, NOEC was determined to be 0.139 mg/L.

 

In a supporting study, long-term toxicity tests of D-8 were performed using Daphnia magna. The Daphnia magna (21 d) chronic toxicity tests were conducted as outlined in Organization for Economic Cooperation and Development (OECD) test guidelines 211 (OECD, 2012). For D. magna chronic toxicity tests, 10 neonates per group were exposed to D-8 (0, 0.06, 0.12, 0.25, 0.5, 1 mg/L). The endpoints were survival of parent animal, first day of neonate production, number of neonates per parent animal, number of neonates per brood, and growth. In D. magna exposed to D-8 for 21 d, no adverse effects of survival and reproduction were observed up to the highest test concentration of 1 mg/L. However, the body length was significantly reduced when exposed to 1 mg/L of D-8. The NOEC value for reproduction of D-8 was 1 mg/L. D-8 was also tested for 7 days in Moina macrocopa, an indigenous species in Asia, in concentrations of 0, 0.01, 0.03, 0.11, 0.33, 1 mg/L. The endpoints were survival of parent animal, first day of neonate production, number of neonates per parent animal, number of neonates per brood. The first day of reproduction was significantly increased at 1 mg/L D-8. The number of young per female, one of the most sensitive endpoints related to the reproduction, was significantly decreased with treatment of 0.3 mg/L of D-8. The NOEC value for reproduction of D-8 was 0.1 mg/L.